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Sample records for normal human trigeminal

  1. Expression of varicella-zoster virus and herpes simplex virus in normal human trigeminal ganglia

    SciTech Connect

    Vafai, A.; Wellish, M.; Devlin, M.; Gilden, D.H. ); Murray, R.S. Veterans Administration Medical Center, Denver, CO )

    1988-04-01

    Lysates of radiolabeled explants from four human trigeminal ganglia were immunoprecipitated with antibodies to varicella-zoster virus (VZV) and to herpes simplex virus. Both herpes simplex virus- and VZV-specific proteins were detected in lysates of all four ganglia. Absence of reactivity in ganglion explants with monoclonal antibodies suggested that herpes simplex virus and VZV were not reactivated during the culture period. In situ hybridization studies demonstrated the presence of RNA transcripts from the VZV immediate early gene 63. This approach to the detection of herpes simplex virus and VZV expression in human ganglia should facilitate analysis of viral RNA and proteins in human sensory ganglia.

  2. Non-Invasive Mapping of Human Trigeminal Brainstem Pathways

    PubMed Central

    Upadhyay, Jaymin; Knudsen, Jamie; Anderson, Julie; Becerra, Lino; Borsook, David

    2008-01-01

    The human trigeminal system mediates facial pain and somatosensory processing. The anatomic location of neuronal substrates and axonal pathways of the trigeminal system have previously been characterized with conventional in vitro methods. The present investigation implemented diffusion tensor imaging (DTI) and probabilistic tractography to first segment the peripheral trigeminal circuitry; trigeminal nerve branches (ophthalmic, maxillary and mandibular nerves), ganglion and nerve root. Subsequent segmentations involved the spinal trigeminal and trigeminal thalamic tracts, which respectively convey information to spinal trigeminal nuclei and ventral thalamic regions. This latter procedure also identified (1) spinal thalamic (anterolateral) system pathways (propagating pain and temperature information from the body); (2) trigeminal lemniscus (touch and face position) and 3) medial lemniscus (touch and limb position). The anatomic location of the identified pain and somatosensory pathways compared well with previous functional findings in human trigeminal system as well as the tract position in human histological cross-sections. Probabilistic tractography may be a useful method to further comprehend the functional and structural properties of trigeminal and other related systems. Application of DTI to map pain and somatosensory pathways in conjunction with a characterization of function properties of pain and somatosensory processing would further define the systematic changes that occur in trigeminal pathology. PMID:18956455

  3. Human herpesvirus 1 meningoencephalitis after trigeminal neuralgia surgery.

    PubMed

    Prim, Núria; Benito, Natividad; Montes, Guillermo; Pomar, Virginia; Molet, Joan; Rabella, Núria

    2013-07-01

    We report a case of human herpesvirus 1 (HHV-1) meningoencephalitis in a patient who underwent trigeminal neuralgia surgery. Although this surgery has been reported to increase the risk of mucocutaneous HHV-1 recurrence, to our knowledge, an association between trigeminal surgery and HHV-1 encephalitis has not been previously described.

  4. Evoked taste thresholds in a normal population and the application of electrogustometry to trigeminal nerve disease.

    PubMed Central

    Grant, R; Ferguson, M M; Strang, R; Turner, J W; Bone, I

    1987-01-01

    No standardised method for taste threshold measurement is available and therefore comparison between clinical studies is difficult. An electrogustometer was evaluated in normal subjects. No sex difference in taste threshold was noted; however, there was a significant elevation in detection threshold with age and smoking. Electrogustometric values both in patients before and after surgery for trigeminal neuralgia and in patients with trigeminal sensory neuropathy were determined. Many patients with trigeminal nerve disorders had abnormal electrogustometric detection thresholds suggesting that there is possibly an accessory taste pathway through the trigeminal nerve, although in some individuals the site of lesion may be in the brain stem. Electrogustometry is a convenient method for clinically assessing taste. Images PMID:3819752

  5. Alphaherpesvirus DNA replication in dissociated human trigeminal ganglia.

    PubMed

    Cohrs, Randall J; Badani, Hussain; Bos, Nathan; Scianna, Charles; Hoskins, Ian; Baird, Nicholas L; Gilden, Don

    2016-10-01

    Analysis of the frequency and PCR-quantifiable abundance of herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) DNA in multiple biological replicates of cells from dissociated randomly distributed human trigeminal ganglia (TG) of four subjects revealed an increase in both parameters and in both viruses during 5 days of culture, with no further change by 10 days. Dissociated TG provides a platform to analyze initiation of latent virus DNA replication within 5 days of culture.

  6. [Jaw opening reflex: a new electrophysiologic method for objective assessment of trigeminal sensory disorders. I. Method and normal values].

    PubMed

    Hassfeld, S; Meinck, H M

    1992-12-01

    Retrospective analysis of trigeminal nerve evoked potentials in 40 consecutive patients, most of them with traumatic nerve lesions, showed that in 12 cases no trigeminal nerve SEP were obtainable, and 11 of the remaining 28 patients had normal trigeminal nerve SEP. Therefore the jaw-opening reflex was investigated as a potential tool for electrophysiologic analysis of facial sensory disturbances. The jaw-opening reflex was investigated in 60 healthy subjects (31 female, 29 male) aged 23-82 years. It was elicited by electrical 0.1 ms square wave pulses delivered to the lower and upper lips and to the infraorbital region on either side at a rate below 1 per 5s. The EMG responses were recorded from the bilateral masseter and temporalis muscles at a moderate voluntary activation. Under these conditions, the jaw-opening reflex reveals itself as two inhibitory pauses of the ongoing EMG on both sides, the onset latency of the first EMG-suppression being 10-15 ms, and of the second 35-50 ms. Particular attention was paid to the stimulus strength at threshold (TR) to evoke the jaw-opening reflex. We found that the jaw-opening reflex was constantly evoked by weak stimuli applied to the 2nd and 3rd trigeminal branches. Bilateral reflex responses with unilateral stimulation were a regular finding. The reflex responses increase with increasing stimulus strength (Fig. 1). Moderate to forcible activation of the jaw closing muscles is a prerequisite for optimum recordings of the jaw-opening reflex (Fig. 2).(ABSTRACT TRUNCATED AT 250 WORDS)

  7. The neuronal correlates of intranasal trigeminal function – An ALE meta-analysis of human functional brain imaging data

    PubMed Central

    Albrecht, Jessica; Kopietz, Rainer; Frasnelli, Johannes; Wiesmann, Martin; Hummel, Thomas; Lundström, Johan N.

    2009-01-01

    Almost every odor we encounter in daily life has the capacity to produce a trigeminal sensation. Surprisingly, few functional imaging studies exploring human neuronal correlates of intranasal trigeminal function exist, and results are to some degree inconsistent. We utilized activation likelihood estimation (ALE), a quantitative voxel-based meta-analysis tool, to analyze functional imaging data (fMRI/PET) following intranasal trigeminal stimulation with carbon dioxide (CO2), a stimulus known to exclusively activate the trigeminal system. Meta-analysis tools are able to identify activations common across studies, thereby enabling activation mapping with higher certainty. Activation foci of nine studies utilizing trigeminal stimulation were included in the meta-analysis. We found significant ALE scores, thus indicating consistent activation across studies, in the brainstem, ventrolateral posterior thalamic nucleus, anterior cingulate cortex, insula, precentral gyrus, as well as in primary and secondary somatosensory cortices – a network known for the processing of intranasal nociceptive stimuli. Significant ALE values were also observed in the piriform cortex, insula, and the orbitofrontal cortex, areas known to process chemosensory stimuli, and in association cortices. Additionally, the trigeminal ALE statistics were directly compared with ALE statistics originating from olfactory stimulation, demonstrating considerable overlap in activation. In conclusion, the results of this meta-analysis map the human neuronal correlates of intranasal trigeminal stimulation with high statistical certainty and demonstrate that the cortical areas recruited during the processing of intranasal CO2 stimuli include those outside traditional trigeminal areas. Moreover, through illustrations of the considerable overlap between brain areas that process trigeminal and olfactory information; these results demonstrate the interconnectivity of flavor processing. PMID:19913573

  8. RNA-Seq Analysis of Human Trigeminal and Dorsal Root Ganglia with a Focus on Chemoreceptors

    PubMed Central

    Flegel, Caroline; Schöbel, Nicole; Altmüller, Janine; Becker, Christian; Tannapfel, Andrea; Hatt, Hanns; Gisselmann, Günter

    2015-01-01

    The chemosensory capacity of the somatosensory system relies on the appropriate expression of chemoreceptors, which detect chemical stimuli and transduce sensory information into cellular signals. Knowledge of the complete repertoire of the chemoreceptors expressed in human sensory ganglia is lacking. This study employed the next-generation sequencing technique (RNA-Seq) to conduct the first expression analysis of human trigeminal ganglia (TG) and dorsal root ganglia (DRG). We analyzed the data with a focus on G-protein coupled receptors (GPCRs) and ion channels, which are (potentially) involved in chemosensation by somatosensory neurons in the human TG and DRG. For years, transient receptor potential (TRP) channels have been considered the main group of receptors for chemosensation in the trigeminal system. Interestingly, we could show that sensory ganglia also express a panel of different olfactory receptors (ORs) with putative chemosensory function. To characterize OR expression in more detail, we performed microarray, semi-quantitative RT-PCR experiments, and immunohistochemical staining. Additionally, we analyzed the expression data to identify further known or putative classes of chemoreceptors in the human TG and DRG. Our results give an overview of the major classes of chemoreceptors expressed in the human TG and DRG and provide the basis for a broader understanding of the reception of chemical cues. PMID:26070209

  9. Latent Herpes Simplex Virus 1 Infection Does Not Induce Apoptosis in Human Trigeminal Ganglia

    PubMed Central

    Lindemann, Anja; Sinicina, Inga; Strupp, Michael; Brandt, Thomas; Hüfner, Katharina

    2015-01-01

    Herpes simplex virus 1 (HSV-1) can establish lifelong latency in human trigeminal ganglia. Latently infected ganglia contain CD8+ T cells, which secrete granzyme B and are thus capable of inducing neuronal apoptosis. Using immunohistochemistry and single-cell reverse transcription-quantitative PCR (RT-qPCR), higher frequency and transcript levels of caspase-3 were found in HSV-1-negative compared to HSV-1-positive ganglia and neurons, respectively. No terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay-positive neurons were detected. The infiltrating T cells do not induce apoptosis in latently infected neurons. PMID:25762734

  10. Dose-Response Functions for the Olfactory, Nasal Trigeminal, and Ocular Trigeminal Detectability of Airborne Chemicals by Humans.

    PubMed

    Cometto-Muñiz, J Enrique; Abraham, Michael H

    2016-01-01

    We gathered from the literature 47 odor and 37 trigeminal (nasal and ocular) chemesthetic psychometric (i.e., detectability or dose-response) functions from a group of 41 chemicals. Vapors delivered were quantified by analytical methods. All functions were very well fitted by the sigmoid (logistic) equation: y = 1 / (1 + e({-(x-C)/D})), where parameter C quantifies the detection threshold concentration and parameter D the steepness of the function. Odor and chemesthetic functions showed no concentration overlap: olfactory functions grew along the parts per billion (ppb by volume) range or lower, whereas trigeminal functions grew along the part per million (ppm by volume) range. Although, on average, odor detectability rose from chance detection to perfect detection within 2 orders of magnitude in concentration, chemesthetic detectability did it within one. For 16 compounds having at least 1 odor and 1 chemesthetic function, the average gap between the 2 functions was 4.6 orders of magnitude in concentration. A quantitative structure-activity relationship (QSAR) using 5 chemical descriptors that had previously described stand-alone odor and chemesthetic threshold values, also holds promise to describe, and eventually predict, olfactory and chemesthetic detectability functions, albeit functions from additional compounds are needed to strengthen the QSAR.

  11. No relevant modulation of TRPV1-mediated trigeminal pain by intranasal carbon dioxide in healthy humans

    PubMed Central

    2013-01-01

    Background Nasal insufflation of CO2 has been shown to exert antinociceptive respectively antihyperalgesic effects in animal pain models using topical capsaicin with activation of TRPV1-receptor positive nociceptive neurons. Clinical benefit from CO2 inhalation in patients with craniofacial pain caused by a putative activation of TRPV1 receptor positive trigeminal neurons has also been reported. These effects are probably mediated via an activation of TRPV1 receptor - positive neurons in the nasal mucosa with subsequent central inhibitory effects (such as conditioned pain modulation). In this study, we aimed to examine the effects of intranasal CO2 on a human model of craniofacial pain elicited by nasal application of capsaicin. Methods In a first experiment, 48 healthy volunteers without previous craniofacial pain received intranasal capsaicin to provoke trigeminal pain elicited by activation of TRVP1 positive nociceptive neurons. Then, CO2 or air was insufflated alternatingly into the nasal cavity at a flow rate of 1 l/min for 60 sec each. In the subsequent experiment, all participants were randomized into 2 groups of 24 each and received either continuous nasal insufflation of CO2 or placebo for 18:40 min after nociceptive stimulation with intranasal capsaicin. In both experiments, pain was rated on a numerical rating scale every 60 sec. Results Contrary to previous animal studies, the effects of CO2 on experimental trigeminal pain were only marginal. In the first experiment, CO2 reduced pain ratings only minimally by 5.3% compared to air if given alternatingly with significant results for the main factor GROUP (F1,47 = 4.438; p = 0.041) and the interaction term TIME*GROUP (F2.6,121.2 = 3.3; p = 0.029) in the repeated-measures ANOVA. However, these effects were abrogated after continuous insufflation of CO2 or placebo with no significant changes for the main factors or the interaction term. Conclusions Although mild modulatory effects of low

  12. Gene therapy for trigeminal pain in mice

    PubMed Central

    Tzabazis, Alexander Z.; Klukinov, Michael; Feliciano, David P.; Wilson, Steven P.; Yeomans, David C.

    2014-01-01

    The aim of this study was to test the efficacy of a single direct injection of viral vector encoding for encephalin to induce a widespread expression of the transgene and potential analgesic effect in trigeminal behavioral pain models in mice. After direct injection of HSV-1 based vectors encoding for human preproenkephalin (SHPE) or the lacZ reporter gene (SHZ.1, control virus) into the trigeminal ganglia in mice, we performed an orofacial formalin test and assessed the cumulative nociceptive behavior at different time points after injection of the viral vectors. We observed an analgesic effect on nociceptive behavior that lasted up to 8 weeks after a single injection of SHPE into the trigeminal ganglia. Control virus injected animals showed nociceptive behavior similar to naïve mice. The analgesic effect of SHPE injection was reversed/attenuated by subcutaneous naloxone injections, a μ-opioid receptor antagonist. SHPE injected mice also showed normalization in withdrawal latencies upon thermal noxious stimulation of inflamed ears after subdermal complete Freund’s adjuvans injection indicating widespread expression of the transgene. Quantitative immunohistochemistry of trigeminal ganglia showed expression of human preproenkephalin after SHPE injection. Direct injection of viral vectors proved to be useful for exploring the distinct pathophysiology of the trigeminal system and could also be an interesting addition to the pain therapists’ armamentarium. PMID:24572785

  13. Induction of varicella zoster virus DNA replication in dissociated human trigeminal ganglia.

    PubMed

    Cohrs, Randall J; Badani, Hussain; Baird, Nicholas L; White, Teresa M; Sanford, Bridget; Gilden, Don

    2017-02-01

    Varicella zoster virus (VZV), a human neurotropic alphaherpesvirus, becomes latent after primary infection and reactivates to produce zoster. To study VZV latency and reactivation, human trigeminal ganglia removed within 24 h after death were mechanically dissociated, randomly distributed into six-well tissue culture plates and incubated with reagents to inactivate nerve growth factor (NGF) or phosphoinositide 3-kinase (PI3-kinase) pathways. At 5 days, VZV DNA increased in control and PI3-kinase inhibitor-treated cultures to the same extent, but was significantly more abundant in anti-NGF-treated cultures (p = 0.001). Overall, VZV DNA replication is regulated in part by an NGF pathway that is PI3-kinase-independent.

  14. Evaluation of Trigeminal Sensitivity to Ammonia in Asthmatics and Healthy Human Volunteers

    PubMed Central

    Petrova, Maja; Diamond, Jeanmarie; Schuster, Benno; Dalton, Pamela

    2009-01-01

    Background Asthmatics often report the triggering or exacerbation of respiratory symptoms following exposure to airborne irritants, which in some cases may result from stimulation of irritant receptors in the upper airways inducing reflexive broncho-constriction. Ammonia (NH3) is a common constituent of commercially available household products, and in high concentration has the potential to elicit sensory irritation in the eyes and upper respiratory tract of humans. The goal of the present study was to evaluate the irritation potential of ammonia in asthmatics and healthy volunteers and to determine whether differences in nasal or ocular irritant sensitivity to ammonia between these two groups could account for the exacerbation of symptoms reported by asthmatics following exposure to an irritant. Methods 25 healthy and 15 mild/moderate persistent asthmatic volunteers, with reported sensitivity to household cleaning products, were evaluated for their sensitivity to the ocular and nasal irritancy of NH3. Lung function was evaluated at baseline and multiple time points following exposure. Results Irritation thresholds did not differ between asthmatics and healthy controls, nor did ratings of odor intensity, annoyance and irritancy following exposure to NH3 concentrations at and above the irritant threshold for longer periods of time (30 sec).Importantly, no changes in lung function occurred following exposure to NH3 for any individuals in either group. Conclusion Despite heightened symptom reports to environmental irritants among asthmatics, the ocular and nasal trigeminal system of mild-moderate asthmatics does not appear to be more sensitive or more reactive than that of non-asthmatics, nor does short duration exposure to ammonia at irritant levels induce changes in lung function. At least in brief exposures, the basis for some asthmatics to experience adverse responses to volatile compounds in everyday life may arise from factors other than trigeminally

  15. The composition of trigeminal nerve branches in normal adult chickens and after debeaking at different ages.

    PubMed

    Dubbeldam, J L; De Bakker, M A; Bout, R G

    1995-06-01

    The long term effects of amputation of the tip of the beak were studied in adult hens that were debeaked on the day of hatching, at the age of 8 d and at 6 wk, by EM analysis of fibre spectra of the medial branch of the ophthalmic nerve and of the intramandibular nerve. Three categories of fibre were distinguished for further analysis, i.e. unmyelinated axons, small myelinated fibres and large myelinated fibres. In normal birds the ophthalmic nerve contains relatively more large fibres than the intramandibular nerve. Amputation consistently results in a reduction of the number of large fibres and a substantial increase in the number of small myelinated fibres. The proportion of unmyelinated axons is rather variable, but is not affected by beak trimming. Age at debeaking has no effect. The observations are inconclusive concerning the possibility of heightened nociception.

  16. Selective retention of herpes simplex virus-specific T cells in latently infected human trigeminal ganglia

    PubMed Central

    Verjans, Georges M. G. M.; Hintzen, Rogier Q.; van Dun, Jessica M.; Poot, Angelique; Milikan, Johannes C.; Laman, Jon D.; Langerak, Anton W.; Kinchington, Paul R.; Osterhaus, Albert D. M. E.

    2007-01-01

    Primary infection with herpes simplex virus 1 (HSV-1) and varicella zoster virus (VZV) results in lifelong latent infections of neurons in sensory ganglia such as the trigeminal ganglia (TG). It has been postulated that T cells retained in TG inhibit reactivation of latent virus. The acquisition of TG specimens of individuals within hours after death offered the unique opportunity to characterize the phenotype and specificity of TG-resident T cells in humans. High numbers of activated CD8+ T cells expressing a late effector memory phenotype were found to reside in latently infected TG. The T cell infiltrate was oligoclonal, and T cells selectively clustered around HSV-1 but not VZV latently infected neurons. Neuronal damage was not observed despite granzyme B expression by the neuron-interacting CD8+ T cells. The TG-resident T cells, mainly CD8+ T cells, were directed against HSV-1 and not to VZV, despite neuronal expression of VZV proteins. The results implicate that herpesvirus latency in human TG is associated with a local, persistent T cell response, comprising activated late effector memory CD8+ T cells that appear to control HSV-1 latency by noncytolytic pathways. In contrast, T cells do not seem to be directly involved in controlling VZV latency in human TG. PMID:17360672

  17. Trigeminal neuralgia

    MedlinePlus

    ... Elsevier Saunders; 2015:chap 117. Zakrzewska JM, Chen HI, Lee JYK. Trigeminal and glossopharyngeal neuralgia. In: McMohan ... A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the ...

  18. Trigeminal neuralgia

    PubMed Central

    Cruccu, Giorgio; Finnerup, Nanna B.; Jensen, Troels S.; Scholz, Joachim; Sindou, Marc; Svensson, Peter; Zakrzewska, Joanna M.; Nurmikko, Turo

    2016-01-01

    Trigeminal neuralgia (TN) is an exemplary condition of neuropathic facial pain. However, formally classifying TN as neuropathic pain based on the grading system of the International Association for the Study of Pain is complicated by the requirement of objective signs confirming an underlying lesion or disease of the somatosensory system. The latest version of the International Classification of Headache Disorders created similar difficulties by abandoning the term symptomatic TN for manifestations caused by major neurologic disease, such as tumors or multiple sclerosis. These diagnostic challenges hinder the triage of TN patients for therapy and clinical trials, and hamper the design of treatment guidelines. In response to these shortcomings, we have developed a classification of TN that aligns with the nosology of other neurologic disorders and neuropathic pain. We propose 3 diagnostic categories. Classical TN requires demonstration of morphologic changes in the trigeminal nerve root from vascular compression. Secondary TN is due to an identifiable underlying neurologic disease. TN of unknown etiology is labeled idiopathic. Diagnostic certainty is graded possible when pain paroxysms occur in the distribution of the trigeminal nerve branches. Triggered paroxysms permit the designation of clinically established TN and probable neuropathic pain. Imaging and neurophysiologic tests that establish the etiology of classical or secondary TN determine definite neuropathic pain. PMID:27306631

  19. Normalization in human somatosensory cortex.

    PubMed

    Brouwer, Gijs Joost; Arnedo, Vanessa; Offen, Shani; Heeger, David J; Grant, Arthur C

    2015-11-01

    Functional magnetic resonance imaging (fMRI) was used to measure activity in human somatosensory cortex and to test for cross-digit suppression. Subjects received stimulation (vibration of varying amplitudes) to the right thumb (target) with or without concurrent stimulation of the right middle finger (mask). Subjects were less sensitive to target stimulation (psychophysical detection thresholds were higher) when target and mask digits were stimulated concurrently compared with when the target was stimulated in isolation. fMRI voxels in a region of the left postcentral gyrus each responded when either digit was stimulated. A regression model (called a forward model) was used to separate the fMRI measurements from these voxels into two hypothetical channels, each of which responded selectively to only one of the two digits. For the channel tuned to the target digit, responses in the left postcentral gyrus increased with target stimulus amplitude but were suppressed by concurrent stimulation to the mask digit, evident as a shift in the gain of the response functions. For the channel tuned to the mask digit, a constant baseline response was evoked for all target amplitudes when the mask was absent and responses decreased with increasing target amplitude when the mask was concurrently presented. A computational model based on divisive normalization provided a good fit to the measurements for both mask-absent and target + mask stimulation. We conclude that the normalization model can explain cross-digit suppression in human somatosensory cortex, supporting the hypothesis that normalization is a canonical neural computation.

  20. Spontaneous trigeminal allodynia in rats: a model of primary headache.

    PubMed

    Oshinsky, Michael L; Sanghvi, Menka M; Maxwell, Christina R; Gonzalez, Dorian; Spangenberg, Rebecca J; Cooper, Marnie; Silberstein, Stephen D

    2012-10-01

    Animal models are essential for studying the pathophysiology of headache disorders and as a screening tool for new therapies. Most animal models modify a normal animal in an attempt to mimic migraine symptoms. They require manipulation to activate the trigeminal nerve or dural nociceptors. At best, they are models of secondary headache. No existing model can address the fundamental question: How is a primary headache spontaneously initiated? In the process of obtaining baseline periorbital von Frey thresholds in a wild-type Sprague-Dawley rat, we discovered a rat with spontaneous episodic trigeminal allodynia (manifested by episodically changing periorbital pain threshold). Subsequent mating showed that the trait is inherited. Animals with spontaneous trigeminal allodynia allow us to study the pathophysiology of primary recurrent headache disorders. To validate this as a model for migraine, we tested the effects of clinically proven acute and preventive migraine treatments on spontaneous changes in rat periorbital sensitivity. Sumatriptan, ketorolac, and dihydroergotamine temporarily reversed the low periorbital pain thresholds. Thirty days of chronic valproic acid treatment prevented spontaneous changes in trigeminal allodynia. After discontinuation, the rats returned to their baseline of spontaneous episodic threshold changes. We also tested the effects of known chemical human migraine triggers. On days when the rats did not have allodynia and showed normal periorbital von Frey thresholds, glycerol trinitrate and calcitonin gene related peptide induced significant decreases in the periorbital pain threshold. This model can be used as a predictive model for drug development and for studies of putative biomarkers for headache diagnosis and treatment.

  1. Evidence of ancillary trigeminal innervation of levator palpebrae in the general population.

    PubMed

    Lehman, A M; Dong, C C; Harries, A M; Patel, A; Honey, C R; Patel, M S

    2014-02-01

    The cranial synkineses are a group of disorders encompassing a variety of involuntary co-contractions of the facial, masticatory, or extraocular muscles that occur during a particular volitional movement. The neuroanatomical pathways for synkineses largely remain undefined. Our studies explored a normal synkinesis long observed in the general population - that of jaw opening during efforts to open the eyelids widely. To document this phenomenon, we observed 186 consecutive participants inserting or removing contact lenses to identify jaw opening. Seeking electrophysiological evidence, in a second study we enrolled individuals undergoing vascular decompression for trigeminal neuralgia or hemifacial spasm, without a history of jaw-winking, ptosis, or strabismus, to record any motor responses in levator palpebrae superioris (LPS) upon stimulation of the trigeminal motor root. Stimulus was applied to the trigeminal motor root while an electrode in levator recorded the response. We found that 37 participants (20%) opened their mouth partially or fully during contact lens manipulation. In the second study, contraction of LPS with trigeminal motor stimulation was documented in two of six patients, both undergoing surgery for trigeminal neuralgia. We speculate these results might provide evidence of an endogenous synkinesis, indicating that trigeminal-derived innervation of levator could exist in a significant minority of the general population. Our observations demonstrate plasticity in the human cranial nerve innervation pattern and may have implications for treating Marcus Gunn jaw-winking.

  2. Subcutaneous Botulinum toxin type A reduces capsaicin-induced trigeminal pain and vasomotor reactions in human skin.

    PubMed

    Gazerani, Parisa; Pedersen, Natalia Spicina; Staahl, Camilla; Drewes, Asbjørn Mohr; Arendt-Nielsen, Lars

    2009-01-01

    The present human study aimed at investigating the effect of subcutaneous administration of Botulinum toxin type A (BoNT/A) on capsaicin-induced trigeminal pain, neurogenic inflammation and experimentally induced cutaneous pain modalities. Fourteen healthy males (26.3+/-2.6 years) were included in this double-blind and placebo-controlled trial. The subjects received subcutaneous BoNT/A (22.5U) and isotonic saline in the mirror sides of their forehead. Pain and neurogenic inflammation was induced by four intradermal injections of capsaicin (100mug/muL) (before, and days 1, 3 and 7 after treatments). The capsaicin-induced pain intensity, pain area, the area of secondary hyperalgesia, the area of visible flare and vasomotor reactions were recorded together with cutaneous heat, electrical and pressure pain thresholds. BoNT/A reduced the capsaicin-induced trigeminal pain intensity compared to saline (F=37.9, P<0.001). The perceived pain area was smaller for the BoNT/A-treated side compared to saline (F=7.8, P<0.05). BoNT/A reduced the capsaicin-induced secondary hyperalgesia (F=5.3, P<0.05) and flare area (F=10.3, P<0.01) compared to saline. BoNT/A reduced blood flow (F(1,26)=109.5, P<0.001) and skin temperature (F(1,26)=63.1, P<0.001) at the capsaicin injection sites compared to saline and its suppressive effect was maximal at days 3 and 7 (P<0.05, post hoc test). BoNT/A elevated cutaneous heat pain thresholds (F=17.1, P<0.001) compared to saline; however, no alteration was recorded for electrical or pressure pain thresholds (P>0.05). Findings from the present study suggest that BoNT/A appears to preferentially target Cfibers and probably TRPV1-receptors, block neurotransmitter release and subsequently reduce pain, neurogenic inflammation and cutaneous heat pain threshold.

  3. Perception of trigeminal mixtures.

    PubMed

    Filiou, Renée-Pier; Lepore, Franco; Bryant, Bruce; Lundström, Johan N; Frasnelli, Johannes

    2015-01-01

    The trigeminal system is a chemical sense allowing for the perception of chemosensory information in our environment. However, contrary to smell and taste, we lack a thorough understanding of the trigeminal processing of mixtures. We, therefore, investigated trigeminal perception using mixtures of 3 relatively receptor-specific agonists together with one control odor in different proportions to determine basic perceptual dimensions of trigeminal perception. We found that 4 main dimensions were linked to trigeminal perception: sensations of intensity, warmth, coldness, and pain. We subsequently investigated perception of binary mixtures of trigeminal stimuli by means of these 4 perceptual dimensions using different concentrations of a cooling stimulus (eucalyptol) mixed with a stimulus that evokes warmth perception (cinnamaldehyde). To determine if sensory interactions are mainly of central or peripheral origin, we presented stimuli in a physical "mixture" or as a "combination" presented separately to individual nostrils. Results showed that mixtures generally yielded higher ratings than combinations on the trigeminal dimensions "intensity," "warm," and "painful," whereas combinations yielded higher ratings than mixtures on the trigeminal dimension "cold." These results suggest dimension-specific interactions in the perception of trigeminal mixtures, which may be explained by particular interactions that may take place on peripheral or central levels.

  4. Chemosensory properties of the trigeminal system.

    PubMed

    Viana, Félix

    2011-01-19

    The capacity of cutaneous, including trigeminal endings, to detect chemicals is known as chemesthesis or cutaneous chemosensation. This sensory function involves the activation of nociceptor and thermoreceptor endings and has a protective or defensive function, as many of these substances are irritants or poisonous. However, humans have also developed a liking for the distinct sharpness or pungency of many foods, beverages, and spices following activation of the same sensory afferents. Our understanding of the cellular and molecular mechanisms of chemosensation in the trigeminal system has experienced enormous progress in the past decade, following the cloning and functional characterization of several ion channels activated by physical and chemical stimuli. This brief review attempts to summarize our current knowledge in this field, including a functional description of various sensory channels, especially TRP channels, involved in trigeminal chemosensitivy. Finally, some of these new findings are discussed in the context of the pathophysiology of trigeminal chemosensation, including pain, pruritus, migraine, cough, airway inflammation, and ophthalmic diseases.

  5. TRPV1 receptor in the human trigeminal ganglion and spinal nucleus: immunohistochemical localization and comparison with the neuropeptides CGRP and SP.

    PubMed

    Quartu, Marina; Serra, Maria Pina; Boi, Marianna; Poddighe, Laura; Picci, Cristina; Demontis, Roberto; Del Fiacco, Marina

    2016-12-01

    This work presents new data concerning the immunohistochemical occurrence of the transient receptor potential vanilloid type-1 (TRPV1) receptor in the human trigeminal ganglion (TG) and spinal nucleus of subjects at different ontogenetic stages, from prenatal life to postnatal old age. Comparisons are made with the sensory neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP). TRPV1-like immunoreactive (LI) material was detected by western blot in homogenates of TG and medulla oblongata of subjects at prenatal and adult stages of life. Immunohistochemistry showed that expression of the TRPV1 receptor is mostly restricted to the small- and medium-sized TG neurons and to the caudal subdivision of the spinal trigeminal nucleus (Sp5C). The extent of the TRPV1-LI TG neuronal subpopulation was greater in subjects at early perinatal age than at late perinatal age and in postnatal life. Centrally, the TRPV1 receptor localized to fibre tracts and punctate elements, which were mainly distributed in the spinal tract, lamina I and inner lamina II of the Sp5C, whereas stained cells were rare. The TRPV1 receptor colocalized partially with CGRP and SP in the TG, and was incompletely codistributed with both neuropeptides in the spinal tract and in the superficial laminae of the Sp5C. Substantial differences were noted with respect to the distribution of the TRPV1-LI structures described in the rat Sp5C and with respect to the temporal expression of the receptor during the development of the rat spinal dorsal horn. The distinctive localization of TRPV1-LI material supports the concept of the involvement of TRPV1 receptor in the functional activity of the protopathic compartment of the human trigeminal sensory system, i.e. the processing and neurotransmission of thermal and pain stimuli.

  6. Spontaneous Trigeminal Allodynia in Rats: A Model of Primary Headache

    PubMed Central

    Oshinsky, Michael L.; Sanghvi, Menka M.; Maxwell, Christina R.; Gonzalez, Dorian; Spangenberg, Rebecca J.; Cooper, Marnie; Silberstein, Stephen D.

    2014-01-01

    Animal models are essential for studying the pathophysiology of headache disorders and as a screening tool for new therapies. Most animal models modify a normal animal in an attempt to mimic migraine symptoms. They require manipulation to activate the trigeminal nerve or dural nociceptors. At best, they are models of secondary headache. No existing model can address the fundamental question: How is a primary headache spontaneously initiated? In the process of obtaining baseline periorbital von Frey thresholds in a wild-type Sprague-Dawley rat, we discovered a rat with spontaneous episodic trigeminal allodynia (manifested by episodically changing periorbital pain threshold). Subsequent mating showed that the trait is inherited. Animals with spontaneous trigeminal allodynia allow us to study the pathophysiology of primary recurrent headache disorders. To validate this as a model for migraine, we tested the effects of clinically proven acute and preventive migraine treatments on spontaneous changes in rat periorbital sensitivity. Sumatriptan, ketorolac, and dihydroergotamine temporarily reversed the low periorbital pain thresholds. Thirty days of chronic valproic acid treatment prevented spontaneous changes in trigeminal allodynia. After discontinuation, the rats returned to their baseline of spontaneous episodic threshold changes. We also tested the effects of known chemical human migraine triggers. On days when the rats did not have allodynia and showed normal periorbital von Frey thresholds, glycerol trinitrate and calcitonin gene related peptide induced significant decreases in the periorbital pain threshold. This model can be used as a predictive model for drug development and for studies of putative biomarkers for headache diagnosis and treatment. PMID:22963523

  7. Pancreastatin molecular forms in normal human plasma.

    PubMed

    Kitayama, N; Tateishi, K; Funakoshi, A; Miyasaka, K; Shimazoe, T; Kono, A; Iwamoto, N; Matsuoka, Y

    1994-01-01

    Circulating molecular forms with pancreastatin (PST)-like immunoreactivity in plasma from normal subjects were examined. An immunoreactive form corresponding to a human PST-like sequence [human chromogranin-A-(250-301)] (hPST-52) and a larger form (mol wt 15-21 kDa) were detected by gel filtration of plasma from normal subjects. On high performance liquid chromatography, predominant immunoreactive forms coeluted with the three larger forms which were purified from the xenograft of human pancreatic islet cell carcinoma cell line QGP-1N cells and with synthetic hPST-52. The fraction containing larger forms purified from xenograft of QGP-1N cells had biological activity equivalent to that of hPST-52 on the inhibition of pancreatic exocrine secretion. These results suggest that the larger molecular forms as well as hPST-52 may be physiologically important circulating forms of PST in human.

  8. Gating of trigemino-facial reflex from low-threshold trigeminal and extratrigeminal cutaneous fibres in humans.

    PubMed Central

    Rossi, A; Scarpini, C

    1992-01-01

    Changes in the size of the test components (R1 and R2) of the trigemino-facial reflex were studied after electrical subliminal conditioning stimulation were applied to the trigeminal, median and sural nerves. After conditioning activation of the trigeminal nerve (below the reflex threshold), the early R1 reflex component showed phasic facilitation, peaking at about 50 ms of interstimulus delay, followed by a long-lasting inhibition recovering at 300-400 ms. The same conditioning stimulation resulted in a monotonic inhibition of the late R2, starting at 15-20 ms, with a maximum at 100-150 ms and lasting 300-400 ms. Intensity threshold for both the R1 and R2 changes ranged from 0.90 to 0.95 times the perception threshold. A similar longlasting inhibition of the R2 reflex response was also seen after conditioning stimulation applied to low-threshold cutaneous afferents of the median and sural nerves. The minimum effective conditioning-test interval was 25-30 ms and 40-45 ms respectively and lasted 600-700 ms. By contrast the early R1 reflex response exhibited a slight long-lasting facilitation with a time course similar to that of the R2 inhibition. The threshold intensity to obtain facilitation of the R1 and inhibition of the R2 test responses after conditioning volley in the median and sural nerves was similar and ranged from 0.9 to 1.2 times the perception threshold. These results demonstrate that low-threshold cutaneous afferents from trigeminal and limb nerves exert powerful control on trigeminal reflex pathways, probably via a common neural substrate. There is evidence that, in addition to any post-synaptic mechanism which might be operating, presynaptic control is a primary factor contributing to these changes. Images PMID:1328539

  9. The scent of salience — Is there olfactory-trigeminal conditioning in humans?

    PubMed Central

    Moessnang, C.; Pauly, K.; Kellermann, T.; Krämer, J.; Finkelmeyer, A.; Hummel, T.; Siegel, S.J.; Schneider, F.; Habel, U.

    2014-01-01

    Pavlovian fear conditioning has been thoroughly studied in the visual, auditory and somatosensory domain, but evidence is scarce with regard to the chemosensory modality. Under the assumption that Pavlovian conditioning relies on the supra-modal mechanism of salience attribution, the present study was set out to attest the existence of chemosensory aversive conditioning in humans as a specific instance of salience attribution. fMRI was performed in 29 healthy subjects during a differential aversive conditioning paradigm. Two odors (rose, vanillin) served as conditioned stimuli (CS), one of which (CS+) was intermittently coupled with intranasally administered CO2. On the neural level, a robust differential response to the CS+ emerged in frontal, temporal, occipito-parietal and subcortical brain regions, including the amygdala. These changes were paralleled by the development of a CS+-specific connectivity profile of the anterior midcingulate cortex (aMCC), which is a key structure for processing salience information in order to guide adaptive response selection. Increased coupling could be found between key nodes of the salience network (anterior insula, neo-cerebellum) and sensorimotor areas, representing putative input and output structures of the aMCC for exerting adaptive motor control. In contrast, behavioral and skin conductance responses did not show significant effects of conditioning, which has been attributed to contingency unawareness. These findings imply substantial similarities of conditioning involving chemosensory and other sensory modalities, and suggest that salience attribution and adaptive control represent a general, modality-independent principle underlying Pavlovian conditioning. PMID:23558094

  10. NORMAL HUMAN VARIATION: REFOCUSSING THE ENHANCEMENT DEBATE

    PubMed Central

    Kahane, Guy; Savulescu, Julian

    2015-01-01

    This article draws attention to several common mistakes in thinking about biomedical enhancement, mistakes that are made even by some supporters of enhancement. We illustrate these mistakes by examining objections that John Harris has recently raised against the use of pharmacological interventions to directly modulate moral decision-making. We then apply these lessons to other influential figures in the debate about enhancement. One upshot of our argument is that many considerations presented as powerful objections to enhancement are really strong considerations in favour of biomedical enhancement, just in a different direction. Another upshot is that it is unfortunate that much of the current debate focuses on interventions that will radically transform normal human capacities. Such interventions are unlikely to be available in the near future, and may not even be feasible. But our argument shows that the enhancement project can still have a radical impact on human life even if biomedical enhancement operated entirely within the normal human range. PMID:23906367

  11. Normal human variation: refocussing the enhancement debate.

    PubMed

    Kahane, Guy; Savulescu, Julian

    2015-02-01

    This article draws attention to several common mistakes in thinking about biomedical enhancement, mistakes that are made even by some supporters of enhancement. We illustrate these mistakes by examining objections that John Harris has recently raised against the use of pharmacological interventions to directly modulate moral decision-making. We then apply these lessons to other influential figures in the debate about enhancement. One upshot of our argument is that many considerations presented as powerful objections to enhancement are really strong considerations in favour of biomedical enhancement, just in a different direction. Another upshot is that it is unfortunate that much of the current debate focuses on interventions that will radically transform normal human capacities. Such interventions are unlikely to be available in the near future, and may not even be feasible. But our argument shows that the enhancement project can still have a radical impact on human life even if biomedical enhancement operated entirely within the normal human range.

  12. Intracranial Trigeminal Schwannoma

    PubMed Central

    2015-01-01

    Intracranial trigeminal schwannomas are rare tumors. Patients usually present with symptoms of trigeminal nerve dysfunction, the most common symptom being facial pain. MRI is the imaging modality of choice and is usually diagnostic in the appropriate clinical setting. The thin T2-weighted CISS 3D axial sequence is important for proper assessment of the cisternal segment of the nerve. They are usually hypointense on T1, hyperintense on T2 with avid enhancement post gadolinium. CT scan is supplementary to MRI, particularly for tumors located in the skull base. Imaging plays a role in diagnosis and surgical planning. In this pictorial essay, we retrospectively reviewed imaging findings in nine patients with pathologically proven trigeminal schwannoma. Familiarity with the imaging findings of intracranial trigeminal schwannoma may help to diagnose this entity. PMID:25924170

  13. 3D Normal Human Neural Progenitor Tissue-Like Assemblies: A Model of Persistent VZV Infection

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas J.

    2013-01-01

    Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus that causes varicella upon primary infection, establishes latency in multiple ganglionic neurons, and can reactivate to cause zoster. Live attenuated VZV vaccines are available; however, they can also establish latent infections and reactivate. Studies of VZV latency have been limited to the analyses of human ganglia removed at autopsy, as the virus is strictly a human pathogen. Recently, terminally differentiated human neurons have received much attention as a means to study the interaction between VZV and human neurons; however, the short life-span of these cells in culture has limited their application. Herein, we describe the construction of a model of normal human neural progenitor cells (NHNP) in tissue-like assemblies (TLAs), which can be successfully maintained for at least 180 days in three-dimensional (3D) culture, and exhibit an expression profile similar to that of human trigeminal ganglia. Infection of NHNP TLAs with cell-free VZV resulted in a persistent infection that was maintained for three months, during which the virus genome remained stable. Immediate-early, early and late VZV genes were transcribed, and low-levels of infectious VZV were recurrently detected in the culture supernatant. Our data suggest that NHNP TLAs are an effective system to investigate long-term interactions of VZV with complex assemblies of human neuronal cells.

  14. Dynamic mapping of normal human hippocampal development.

    PubMed

    Gogtay, Nitin; Nugent, Tom F; Herman, David H; Ordonez, Anna; Greenstein, Deanna; Hayashi, Kiralee M; Clasen, Liv; Toga, Arthur W; Giedd, Jay N; Rapoport, Judith L; Thompson, Paul M

    2006-01-01

    The hippocampus, which plays an important role in memory functions and emotional responses, has distinct subregions subserving different functions. Because the volume and shape of the hippocampus are altered in many neuropsychiatric disorders, it is important to understand the trajectory of normal hippocampal development. We present the first dynamic maps to reveal the anatomical sequence of normal human hippocampal development. A novel hippocampal mapping technique was applied to a database of prospectively obtained brain magnetic resonance imaging (MRI) scans (100 scans in 31 children and adolescents), scanned every 2 yr for 6-10 yr between ages 4 and 25. Our results establish that the structural development of the human hippocampus is remarkably heterogeneous, with significant differences between posterior (increase over time) and anterior (loss over time) subregions. These distinct developmental trajectories of hippocampal subregions may parallel differences in their functional development.

  15. Uncommon Cause of Trigeminal Neuralgia: Tentorial Ossification over Trigeminal Notch

    PubMed Central

    Bang, Sun Woo; Han, Kyung Ream; Kim, Seung Ho; Jeong, Won Ho; Kim, Eun Jin; Choi, Jin Wook; Kim, Chan

    2015-01-01

    Ossification of the tentorium cerebelli over the trigeminal notch is rare, but it may cause compression of the trigeminal nerve, leading to trigeminal neuralgia (TN). We were unable to find any previously reported cases with radiological evaluation, although we did find one case with surgically proven ossification of the tentorium cerebelli. Here, we present a case of TN caused by tentorial ossification over the trigeminal notch depicted on magnetic resonance imaging (MRI) and computed tomography (CT). PMID:26380124

  16. [Pharmacotherapy of trigeminal neuralgia].

    PubMed

    Ramirez, H; Martinez, C; Oliva, J; Montini, C

    1989-12-01

    The efficacy of drug treatment on 119 patients with trigeminal neuralgia is reported in the present paper. Among them, 112 were idiopathic trigeminal neuralgias while only 7 cases were secondary trigeminal neuralgias. All patients were treated with drugs at different stages of the evolution of the neuralgia. Carbamazepine was used on all patients. 12.6% was treated with imipramine (tricyclic antidepressive drug), 4 patients received amphetamines due to psychiatric emergencies, 4 patients were treated with phenytoin before this study and three patients received baclofen during short periods of follow-up. Drug therapy was the only treatment method in 51 patients. In 43 patients it was combined with peripheral surgical treatments including injections of alcohol and neurectomies. 16.8% of the patients were treated with drugs and acupuncture; the results of this experience will be reported in a future paper. Only 4.2% (5 patients) underwent neurosurgical treatment: one ponto cerebellar angle tumour, one electrocoagulation of the gasserian ganglion through the stereotaxic method and three cases of microvascular decompression of the trigeminal root. Clinical, pharmacological and neurophysiological aspects of trigeminal neuralgia pharmacotherapy are discussed.

  17. Neuronal development in the trigeminal mesencephalic nucleus of the duck under normal and hypothyroid states: I. A light microscopic morphometric analysis.

    PubMed

    Narayanan, Y; Narayanan, C H

    1987-01-01

    Light microscopic morphometric procedures were used in order to examine the effects of propylthiouracil (PTU) on the development of the mesencephalic nucleus of the trigeminal nerve in the duck. A single vascular injection of a 0.2% solution of PTU was administered at a dosage of 2 microliter/gm embryo weight on embryonic day nine (E9). Control embryos received a similar dose of Ringer's solution. The following parameters of cytodifferentiation of cells of the mesencephalic nucleus of V were studied: somal area profiles, nuclear area, and nuclear cytoplasmic ratios. In addition, the frequency of beak clapping was recorded from E16. Significant differences were observed in somal area profiles in the experimental group at E16 and E18 and in nuclear area profiles from E16 through hatching. Beak activity in the experimental embryos was drastically reduced. It is concluded that PTU induces a retardation in the differentiation of cells of the mesencephalic nucleus of V which may lead to behavior deficits as evidenced by reduction of beak activity. These observations provide a basis for the study of interactions between thyroid hormone and specific neuronal systems in the emergence of an adaptive function.

  18. The variability problem of normal human walking.

    PubMed

    Simonsen, Erik B; Alkjær, Tine

    2012-03-01

    Previous investigations have suggested considerable inter-individual variability in the time course pattern of net joint moments during normal human walking, although the limited sample sizes precluded statistical analyses. The purpose of the present study was to obtain joint moment patterns from a group of normal subjects and to test whether or not the expected differences would prove to be statistically significant. Fifteen healthy male subjects were recorded on video while they walked across two force platforms. Ten kinematic and kinetic parameters were selected and input to a statistical cluster analysis to determine whether or not the 15 subjects could be divided into different 'families' (clusters) of walking strategy. The net joint moments showed a variability corroborating earlier reports. The cluster analysis showed that the 15 subjects could be grouped into two clusters of 5 and 10 subjects, respectively. Five parameters differed significantly, so the group of 5 subjects was characterized by (1) a higher peak knee joint extensor moment, (2) more flexed knee joint angle at heel strike, (3) during the whole stance phase, (4) lower peak knee joint flexor moment and (5) lower ankle joint angle at flat foot position. Calculation of bone-on-bone forces in the knee joint showed a value of 64 N/kg body weight in the K+ group and 55 N/kg in the K- group (p<0.05). It is unknown if differences of similar magnitude contribute to early joint degeneration in some individuals while not in others.

  19. Transcutaneous trigeminal nerve stimulation induces a long-term depression-like plasticity of the human blink reflex.

    PubMed

    Pilurzi, Giovanna; Mercante, Beniamina; Ginatempo, Francesca; Follesa, Paolo; Tolu, Eusebio; Deriu, Franca

    2016-02-01

    The beneficial effects of trigeminal nerve stimulation (TNS) on several neurological disorders are increasingly acknowledged. Hypothesized mechanisms include the modulation of excitability in networks involved by the disease, and its main site of action has been recently reported at brain stem level. Aim of this work was to test whether acute TNS modulates brain stem plasticity using the blink reflex (BR) as a model. The BR was recorded from 20 healthy volunteers before and after 20 min of cyclic transcutaneous TNS delivered bilaterally to the infraorbital nerve. Eleven subjects underwent sham-TNS administration and were compared to the real-TNS group. In 12 subjects, effects of unilateral TNS were tested. The areas of the R1 and R2 components of the BR were recorded before and after 0 (T0), 15 (T15), 30 (T30), and 45 (T45) min from TNS. In three subjects, T60 and T90 time points were also evaluated. Ipsi- and contralateral R2 areas were significantly suppressed after bilateral real-TNS at T15 (p = 0.013), T30 (p = 0.002), and T45 (p = 0.001), while R1 response appeared unaffected. The TNS-induced inhibitory effect on R2 responses lasted up to 60 min. Real- and sham-TNS protocols produced significantly different effects (p = 0.005), with sham-TNS being ineffective at any time point tested. Bilateral TNS was more effective (p = 0.009) than unilateral TNS. Acute TNS induced a bilateral long-lasting inhibition of the R2 component of the BR, which resembles a long-term depression-like effect, providing evidence of brain stem plasticity produced by transcutaneous TNS. These findings add new insight into mechanisms of TNS neuromodulation and into physiopathology of those neurological disorders where clinical benefits of TNS are recognized.

  20. Trigeminal autonomic cephalgias

    PubMed Central

    2012-01-01

    Summary points 1. Trigeminal autonomic cephalgias (TACs) are headaches/facial pains classified together based on:a suspected common pathophysiology involving the trigeminovascular system, the trigeminoparasympathetic reflex and centres controlling circadian rhythms;a similar clinical presentation of trigeminal pain, and autonomic activation. 2. There is much overlap in the diagnostic features of individual TACs. 3. In contrast, treatment response is relatively specific and aids in establishing a definitive diagnosis. 4. TACs are often presentations of underlying pathology; all patients should be imaged. 5. The aim of the article is to provide the reader with a broad introduction to, and an overview of, TACs. The reading list is extensive for the interested reader. PMID:26516482

  1. The effects of Botulinum Toxin type A on capsaicin-evoked pain, flare, and secondary hyperalgesia in an experimental human model of trigeminal sensitization.

    PubMed

    Gazerani, Parisa; Staahl, Camilla; Drewes, Asbjøn M; Arendt-Nielsen, Lars

    2006-06-01

    The trigeminovascular system is involved in migraine. Efficacy of Botulinum Toxin type A (BoNT-A) in migraine has been investigated in clinical studies but the mechanism of action remains unexplored. It is hypothesized that BoNT-A inhibits peripheral sensitization of nociceptive fibers and indirectly reduces central sensitization. We examined the effect of intramuscular injection of BoNT-A on an experimental human model of trigeminal sensitization induced by intradermal capsaicin injection to the forehead. BoNT-A (BOTOX) or saline was injected intramuscularly in precranial, neck and shoulder muscles to 32 healthy male volunteers in a double blind-randomized manner. Intradermally capsaicin-induced pain, flare and secondary hyperalgesia were obtained before and 1, 4 and 8 weeks after the above treatments. A significant suppressive effect of BoNT-A on pain, flare and hyperalgesia area was observed. The pain intensity area was significantly smaller in BoNT-A group (9.16+/-0.83 cm x s) compared to saline group (15.41+/-0.83cm x s) (P=0.011). The flare area was also reduced significantly in BoNT-A group (29.81+/-0.69 cm2) compared to saline group (39.71+/-0.69 cm2) (P<0.001). Similarly, the mean area of secondary hyperalgesia was significantly smaller in BoNT-A group (4.25+/-0.91 cm2) compared to saline group (7.03+/-0.91 cm2) (P=0.040). Post hoc analysis showed significant differences across the trials with a remarkable suppression effect of BoNT-A on capsaicin-induced sensory and vasomotor reactions as early as week1 (P<0.001). BoNT-A presented suppressive effects on the trigeminal/cervical nociceptive system activated by intradermal injection of capsaicin to the forehead. The effects are suggested to be caused by a local peripheral effect of BoNT-A on cutaneous nociceptors.

  2. Analysis of Individual Human Trigeminal Ganglia for Latent Herpes Simplex Virus Type 1 and Varicella-Zoster Virus Nucleic Acids Using Real-Time PCR

    PubMed Central

    Cohrs, Randall J.; Randall, Jessica; Smith, John; Gilden, Donald H.; Dabrowski, Christine; van der Keyl, Harjeet; Tal-Singer, Ruth

    2000-01-01

    Herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV) establish latent infections in the peripheral nervous system following primary infection. During latency both virus genomes exhibit limited transcription, with the HSV-1 LATs and at least four VZV transcripts consistently detected in latently infected human ganglia. In this study we used real-time PCR quantitation to determine the viral DNA copy number in individual trigeminal ganglia (TG) from 17 subjects. The number of HSV-1 genomes was not significantly different between the left and right TG from the same individual and varied per subject from 42.9 to 677.9 copies per 100 ng of DNA. The number of VZV genomes was also not significantly different between left and right TG from the same individual and varied per subject from 37.0 to 3,560.5 copies per 100 ng of DNA. HSV-1 LAT transcripts were consistently detected in ganglia containing latent HSV-1 and varied in relative expression by >500-fold. Of the three VZV transcripts analyzed, only transcripts mapping to gene 63 were consistently detected in latently infected ganglia and varied in relative expression by >2,000-fold. Thus, it appears that, similar to LAT transcription in HSV-1 latently infected ganglia, VZV gene 63 transcription is a hallmark of VZV latency. PMID:11090142

  3. Normal and abnormal human vestibular ocular function

    NASA Technical Reports Server (NTRS)

    Peterka, R. J.; Black, F. O.

    1986-01-01

    The major motivation of this research is to understand the role the vestibular system plays in sensorimotor interactions which result in spatial disorientation and motion sickness. A second goal was to explore the range of abnormality as it is reflected in quantitative measures of vestibular reflex responses. The results of a study of vestibular reflex measurements in normal subjects and preliminary results in abnormal subjects are presented in this report. Statistical methods were used to define the range of normal responses, and determine age related changes in function.

  4. Using Diffusion Tensor Imaging to Evaluate Microstructural Changes and Outcomes after Radiofrequency Rhizotomy of Trigeminal Nerves in Patients with Trigeminal Neuralgia

    PubMed Central

    Chen, Shu-Tian; Yang, Jen-Tsung; Yeh, Mei-Yu; Weng, Hsu-Huei; Chen, Chih-Feng

    2016-01-01

    Trigeminal neuralgia is characterized by facial pain that may be sudden, intense, and recurrent. Our aim was to investigate microstructural tissue changes of the trigeminal nerve in patients with trigeminal neuralgia resulting from neurovascular compression by diffusion tensor imaging, and to test the predictive value of diffusion tensor imaging for determining outcomes after radiofrequency rhizotomy. Forty-three patients with trigeminal neuralgia were recruited, and diffusion tensor imaging was performed before radiofrequency rhizotomy. By selecting the cisternal segment of the trigeminal nerve manually, we measured the volume of trigeminal nerve, fractional anisotropy, apparent diffusion coefficient, axial diffusivity, and radial diffusivity. The apparent diffusion coefficient and mean value of fractional anisotropy, axial diffusivity, and radial diffusivity were compared between the affected and normal side in the same patient, and were correlated with pre-rhizotomy and post-rhizotomy visual analogue scale pain scores. The results showed the affected side had significantly decreased fractional anisotropy, increased apparent diffusion coefficient and radial diffusivity, and no significant change of axial diffusivity. The volume of the trigeminal nerve on affected side was also significantly smaller. There was a trend of fractional anisotropy reduction and visual analogue scale pain score reduction (P = 0.072). The results suggest that demyelination without axonal injury, and decreased size of the trigeminal nerve, are the microstructural abnormalities of the trigeminal nerve in patients with trigeminal neuralgia caused by neurovascular compression. The application of diffusion tensor imaging in understanding the pathophysiology of trigeminal neuralgia, and predicting the treatment effect has potential and warrants further study. PMID:27997548

  5. Power flow in normal human voice production

    NASA Astrophysics Data System (ADS)

    Krane, Michael

    2016-11-01

    The principal mechanisms of energy utilization in voicing are quantified using a simplified model, in order to better define voice efficiency. A control volume analysis of energy utilization in phonation is presented to identify the energy transfer mechanisms in terms of their function. Conversion of subglottal airstream potential energy into useful work done (vocal fold vibration, flow work, sound radiation), and into heat (sound radiation absorbed by the lungs, glottal jet dissipation) are described. An approximate numerical model is used to compute the contributions of each of these mechanisms, as a function of subglottal pressure, for normal phonation. Acknowledge support of NIH Grant 2R01DC005642-10A1.

  6. Autophagy in term normal human placentas.

    PubMed

    Signorelli, P; Avagliano, L; Virgili, E; Gagliostro, V; Doi, P; Braidotti, P; Bulfamante, G P; Ghidoni, R; Marconi, A M

    2011-06-01

    Autophagy is an inducible catabolic process that responds to environment and is essential for cell survival during stress, starvation and hypoxia. Its function in the human placenta it is not yet understood. We collected 14 placentas: 7 at vaginal delivery and 7 at elective caesarean section after uneventful term pregnancies. The presence of autophagy was assessed in different placental areas by immunoblotting, immunohistochemistry and electron microscopy. We found that autophagy is significantly higher in placentas obtained from cesarean section than in those from vaginal delivery. Moreover there is a significant inverse relationship between autophagy and umbilical arterial glucose concentration.

  7. Acute peripheral facial palsy: is there a trigeminal nerve involvement?

    PubMed

    Uluduz, Derya; Kiziltan, Meral E; Akalin, Mehmet Ali

    2010-07-26

    The aim of this study was to investigate trigeminal nerve involvement in patients with peripheral facial palsy. In total, 25 patients with facial nerve palsy and 19 controls were tested by electrophysiological methods regarding their facial and trigeminal nerve functions within 1 month after disease onset. The presence of an abnormal blink reflex was determined in patients with peripheral facial palsy by comparing paralytic and non-paralytic sides (12.3+/-1.1 and 10.8+/-1.3, respectively; p=0.001). However, the average masseter inhibitory reflex difference between the paretic and non-paralytic sides of patients compared with the corresponding side-to-side comparison for controls was not statistically significant. The masseter inhibitory reflex response was abnormal in some cases. These findings suggest that the masseter inhibitory reflex, a trigemino-trigeminal reflex, was normal in most of our patients with peripheral facial palsy, but may be abnormal in individual cases. Our study showed that subclinical disorders affecting the trigeminal pathways occur in individual patients with idiopathic facial palsy, while the majority of patients have no trigeminal nerve involvement.

  8. Trigeminal neuralgia - diagnosis and treatment.

    PubMed

    Maarbjerg, Stine; Di Stefano, Giulia; Bendtsen, Lars; Cruccu, Giorgio

    2017-01-01

    Introduction Trigeminal neuralgia (TN) is characterized by touch-evoked unilateral brief shock-like paroxysmal pain in one or more divisions of the trigeminal nerve. In addition to the paroxysmal pain, some patients also have continuous pain. TN is divided into classical TN (CTN) and secondary TN (STN). Etiology and pathophysiology Demyelination of primary sensory trigeminal afferents in the root entry zone is the predominant pathophysiological mechanism. Most likely, demyelination paves the way for generation of ectopic impulses and ephaptic crosstalk. In a significant proportion of the patients, the demyelination is caused by a neurovascular conflict with morphological changes such as compression of the trigeminal root. However, there are also other unknown etiological factors, as only half of the CTN patients have morphological changes. STN is caused by multiple sclerosis or a space-occupying lesion affecting the trigeminal nerve. Differential diagnosis and treatment Important differential diagnoses include trigeminal autonomic cephalalgias, posttraumatic or postherpetic pain and other facial pains. First line treatment is prophylactic medication with sodium channel blockers, and second line treatment is neurosurgical intervention. Future perspectives Future studies should focus on genetics, unexplored etiological factors, sensory function, the neurosurgical outcome and complications, combination and neuromodulation treatment as well as development of new drugs with better tolerability.

  9. Typical and atypical neurovascular relations of the trigeminal nerve in the cerebellopontine angle: an anatomical study.

    PubMed

    Rusu, M C; Ivaşcu, R V; Cergan, R; Păduraru, D; Podoleanu, L

    2009-08-01

    The aim of the present study was to anatomically evaluate in adults the neurovascular trigeminal relations in the cerebellopontine angle (CPA), from a morphological and topographical perspective and thus to improve, detail and debate the pre-existing information, with educational and surgical implications. For the present anatomical study we performed bilateral dissections on 20 human adult skull bases, in formalin-fixed cadavers, at the level of the cerebellopontine angle, using the anatomical superior approach; we also studied 20 additional drawn specimens-cerebellum and brainstems, from autopsied cadavers, in order to better document the vasculature at the trigeminal root entry zone (REZ). The most constant but not exclusive neurovascular relations of the trigeminal nerves were those with the superior cerebellar artery (SCA) and the superior petrosal vein (the petrosal vein of Dandy). The regular possibility for the SCA to appear divided into a medial and a lateral branch and these to represent individual trigeminal relations at the level of the pontine cistern or REZ must not be neglected. The petrosal vein tributaries can also represent superior, inferior, or interradicular trigeminal relations. Arterioles emerging from the SCA or the anterior inferior cerebellar artery (AICA) represented trigeminal relations either at the REZ or were coursing between the trigeminal roots. A dissected specimen presented a radicular trigeminal artery emerging from the basilar artery and entering the trigeminal cavum inferior to the nerve. Another specimen presented two bony lamellae superior to the trigeminal nerve at the entrance in the trigeminal cavum-these lamellae were embedded within the lateral border of tentorium cerebelli and the posterior petroclinoid ligament. So we bring here an evidence-based support extremely useful not only for specialists dealing with this area but also for educational purposes. It appears important not only to consider the typical anatomy at

  10. Bilateral sensory deprivation of trigeminal afferent fibres on corticomotor control of human tongue musculature: a preliminary study.

    PubMed

    Kothari, M; Baad-Hansen, L; Svensson, P

    2016-09-01

    Transcranial magnetic stimulation (TMS) has demonstrated changes in motor evoked potentials (MEPs) in human limb muscles following modulation of sensory afferent inputs. The aim of this study was to determine whether bilateral local anaesthesia (LA) of the lingual nerve affects the excitability of the tongue motor cortex (MI) as measured by TMS. The effect on MEPs after bilateral LA of the lingual nerve was studied, while the first dorsal interosseous (FDI) muscle served as a control in ten healthy participants. MEPs were measured on the right side of the tongue dorsum in four different conditions: (i) immediately prior to anaesthesia (baseline), (ii) during bilateral LA block of the lingual nerve, (iii) after anaesthesia had subjectively subsided (recovery) and (iv) 3 h after bilateral lingual block injection. MEPs were assessed using stimulus-response curves in steps of 10% of motor threshold (T). Eight stimuli were given at each stimulus level. The amplitudes of the tongue MEPs were significantly influenced by the stimulus intensity (P < 0·001) but not by condition (P = 0·186). However, post hoc tests showed that MEPS were statistically significantly higher during bilateral LA block condition compared with baseline at T + 40%, T + 50% and T + 60% (P < 0·028) and also compared with recovery at T + 60% (P = 0·010) as well as at 3 h after injection at T + 50% and T + 60% (P < 0·029). Bilateral LA block of the lingual nerve seems to be associated with a facilitation of the corticomotor pathways related to the tongue musculature.

  11. Immunohistochemical characterization of FHIT expression in normal human tissues

    PubMed Central

    Kujan, Omar; Abuderman, Abdulwahab; Al-Shawaf, Ahmad Zahi

    2016-01-01

    Background Fragile histidine triad (FHIT) is a tumor suppressor gene that is commonly inactivated in human tumors. Interestingly, the normal pattern of FHIT expression is largely unknown. Aim This study is aimed to characterize the expression of FHIT protein in normal human tissues. Materials and methods A total of 119 normal human tissue specimens were analyzed for the FHIT expression using immunohistochemistry technique. The inclusion criteria included: normal/inflammatory tissue with no evidence of cellular atypia. Results All studied specimens were stained positively with FHIT and showed either nuclear or cytoplasmic expression. Interestingly, the pattern of FHIT staining was similar among different specimens from each organ. FHIT is located predominantly in the nucleus, although cytoplasmic staining is also present in some cell types. Oral squamous epithelium, breast ductal epithelium, squamous and tubal metaplastic epithelium of the uterine cervix, esophageal squamous epithelium, salivary glands, and bronchial epithelia all strongly expressed the nuclear protein. In connective tissue, FHIT has shown strong cytoplasmic expression in histocytes including macrophages and dendritic cells, fibroblasts, and myofibroblasts. Conclusion Documentation of the pattern of FHIT expression in normal tissues will contribute to our understanding of the normal function of this protein and to interpretation of potentially altered FHIT expression in human tumors. PMID:28250975

  12. Historical characterization of trigeminal neuralgia.

    PubMed

    Eboli, Paula; Stone, James L; Aydin, Sabri; Slavin, Konstantin V

    2009-06-01

    TRIGEMINAL NEURALGIA IS a well known clinical entity characterized by agonizing, paroxysmal, and lancinating facial pain, often triggered by movements of the mouth or eating. Historical reviews of facial pain have attempted to describe this severe pain over the past 2.5 millennia. The ancient Greek physicians Hippocrates, Aretaeus, and Galen, described kephalalgias, but their accounts were vague and did not clearly correspond with what we now term trigeminal neuralgia. The first adequate description of trigeminal neuralgia was given in 1671, followed by a fuller description by physician John Locke in 1677. André described the convulsive-like condition in 1756, and named it tic douloureux; in 1773, Fothergill described it as "a painful affection of the face;" and in 1779, John Hunter more clearly characterized the entity as a form of "nervous disorder" with reference to pain of the teeth, gums, or tongue where the disease "does not reside." One hundred fifty years later, the neurological surgeon Walter Dandy equated neurovascular compression of the trigeminal nerve with trigeminal neuralgia.

  13. Decorin and biglycan of normal and pathologic human corneas

    NASA Technical Reports Server (NTRS)

    Funderburgh, J. L.; Hevelone, N. D.; Roth, M. R.; Funderburgh, M. L.; Rodrigues, M. R.; Nirankari, V. S.; Conrad, G. W.

    1998-01-01

    PURPOSE: Corneas with scars and certain chronic pathologic conditions contain highly sulfated dermatan sulfate, but little is known of the core proteins that carry these atypical glycosaminoglycans. In this study the proteoglycan proteins attached to dermatan sulfate in normal and pathologic human corneas were examined to identify primary genes involved in the pathobiology of corneal scarring. METHODS: Proteoglycans from human corneas with chronic edema, bullous keratopathy, and keratoconus and from normal corneas were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), quantitative immunoblotting, and immunohistology with peptide antibodies to decorin and biglycan. RESULTS: Proteoglycans from pathologic corneas exhibit increased size heterogeneity and binding of the cationic dye alcian blue compared with those in normal corneas. Decorin and biglycan extracted from normal and diseased corneas exhibited similar molecular size distribution patterns. In approximately half of the pathologic corneas, the level of biglycan was elevated an average of seven times above normal, and decorin was elevated approximately three times above normal. The increases were associated with highly charged molecular forms of decorin and biglycan, indicating modification of the proteins with dermatan sulfate chains of increased sulfation. Immunostaining of corneal sections showed an abnormal stromal localization of biglycan in pathologic corneas. CONCLUSIONS: The increased dermatan sulfate associated with chronic corneal pathologic conditions results from stromal accumulation of decorin and particularly of biglycan in the affected corneas. These proteins bear dermatan sulfate chains with increased sulfation compared with normal stromal proteoglycans.

  14. Collagen polymorphism in normal and cirrhotic human liver.

    PubMed Central

    Seyer, J M; Hutcheson, E T; Kang, A H

    1977-01-01

    Collagens in normal human liver and in alcoholic cirrhotic liver were investigated. Collagens were solubilized by limited proteolysis with pepsin under nondenaturing conditions, and after purification, were fractionated into types I and III by selective precipitation with NaCl. After carboxymethyl cellulose and agarose chromatography, the resulting alpha-chains from each of the collagen types were analyzed with respect to their amino acid and carbohydrate compositions. A comparison of the results obtained from normal liver with those from the diseases organ revealed no significant differences. The isolated human liver alpha1(I) and alpha1(III) chains were digested with CNBr and the generated peptides were separated and purified by a combination of ion-exchange and molecular sieve chromatography. The molecular weight and the amino acid and the carbohydrate compositions of each of the peptides were identical to those of the corresponding human skin peptides except for the slightly higher content of hydroxylysine in some of the peptides. The relative content of type III in relation to type I collagen in both normal anc cirrhotic liver was determined by digesting washed liver homogenates directly with CNBr and quantitating the resultant alpha1(I) and alpha 1(III) peptides after chromatographic separation. The relative quantities of these peptides indicated that normal human liver contained an average of 47% type III, with the remainder being type I. Cirrhotic liver, on the other hand, contained a significantly smaller proportion of type III, ranging from 18 to 34% in different samples, with a corresponding increase in type I. These findings indicate that although the amino acid and carbohydrate compositions of collagens deposited in cirrhotic liver are normal, the fibrotic process of alcoholic liver disease in humans is accompanied by an alteration in tissue collagen polymorphism, and suggest that the observed alterations may have pathogenetic implications. PMID:833273

  15. Detection of human cytomegalovirus in normal and neoplastic breast epithelium

    PubMed Central

    2010-01-01

    Introduction Human cytomegalovirus (HCMV) establishes a persistent life-long infection, and can cause severe pathology in the fetus and the immunocompromised host[1]. Breast milk is the primary route of transmission in humans worldwide, and breast epithelium is thus a likely site of persistent infection and/or reactivation, though this phenomenon has not previously been demonstrated. Increasing evidence indicates HCMV infection can modulate signaling pathways associated with oncogenesis. We hypothesized that persistent HCMV infection occurs in normal adult breast epithelium and that persistent viral expression might be associated with normal and neoplastic ductal epithelium. Methods Surgical biopsy specimens of normal breast (n = 38) breast carcinoma (n = 39) and paired normal breast from breast cancer patients (n = 21) were obtained. Specimens were evaluated by immunohistochemistry, in situ hybridization, PCR and DNA sequencing for evidence of HCMV antigens and nucleic acids. Results We detected HCMV expression specifically in glandular epithelium in 17/27 (63%) of normal adult breast cases evaluated. In contrast, HCMV expression was evident in the neoplastic epithelium of 31/32 (97%) patients with ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) cases evaluated (p = 0.0009). Conclusions These findings are the first to demonstrate that persistent HCMV infection occurs in breast epithelium in a significant percentage of normal adult females. HCMV expression was also evident in neoplastic breast epithelium in a high percentage of normal and neoplastic breast tissues obtained from breast cancer patients, raising the possibility that viral infection may be involved in the neoplastic process. PMID:21429243

  16. Trigeminal trophic syndrome with histopathologic correlation.

    PubMed

    Dolohanty, Lindsey B; Richardson, Steven J; Herrmann, David N; Markman, John; Mercurio, Mary Gail

    2015-03-01

    We present the case of a 49-year-old woman with trigeminal trophic syndrome (TTS), also known as trophic trigeminal neuralgia, trigeminal neurotrophic ulceration, and/or trigeminal neuropathy with nasal ulceration. Our case represents an uncommon report of intractable itching and chronic pain associated with TTS. Emphasis was placed on skin biopsy histology, which revealed no neuronal innervation of the affected scalp despite reports of intractable itching and chronic pain. Trigeminal trophic syndrome of the V1 branch of the trigeminal nerve secondary to herpes zoster (HZ) with correlated histology is described. This article provides a discussion of TTS and correlated histology as well as a brief discussion of intractable itching and postherpetic neuralgia.

  17. [Trigeminal neuralgia secondary to petrous endostosis].

    PubMed

    Mata-Gómez, Jacinto; Royano-Sánchez, Manuel; Bejarano-Parra, Macarena; Gilete-Tejero, Ignacio; Rico-Cotelo, María; Ortega-Martínez, Marta

    2017-03-10

    Arterial neurovascular compression is hypothesised to be the main cause of primary trigeminal neuralgia. Although it is the most common cause, other pathologies, such as tumours in the cerebellopontine angle, can cause trigeminal pain. We report a case of a 44-year-old female patient with right trigeminal neuralgia without satisfactory response to medical treatment. Cerebral MRI showed no structural injuries. During microvascular decompression of the trigeminal nerve, endostosis of the internal aspect of the petrous bone was found to compress the trigeminal nerve. The pain disappeared completely in the early postsurgical period, after the complete drilling of the endostosis and microvascular decompression. The patient remains asymptomatic one year later. Endostosis of the petrous bone is a rare cause of trigeminal neuralgia. A proper review of preoperative studies would enable the definitive surgical approach to be optimised.

  18. Controlled thermocoagulation in trigeminal neuralgia.

    PubMed Central

    Mittal, B; Thomas, D G

    1986-01-01

    Results of 280 radiofrequency lesions on 229 patients with trigeminal neuralgia are presented with three months to eight years (average 3.8 years) follow up. The patients were aged from 18-91 years. There was a high overall success rate of 94%. The complication rate has been low, with sensory paraesthesiae the commonest (15%) and cranial nerve palsies very rare (2.4%) compared to other reported series. PMID:3746327

  19. Super Normal Vector for Human Activity Recognition with Depth Cameras.

    PubMed

    Yang, Xiaodong; Tian, YingLi

    2017-05-01

    The advent of cost-effectiveness and easy-operation depth cameras has facilitated a variety of visual recognition tasks including human activity recognition. This paper presents a novel framework for recognizing human activities from video sequences captured by depth cameras. We extend the surface normal to polynormal by assembling local neighboring hypersurface normals from a depth sequence to jointly characterize local motion and shape information. We then propose a general scheme of super normal vector (SNV) to aggregate the low-level polynormals into a discriminative representation, which can be viewed as a simplified version of the Fisher kernel representation. In order to globally capture the spatial layout and temporal order, an adaptive spatio-temporal pyramid is introduced to subdivide a depth video into a set of space-time cells. In the extensive experiments, the proposed approach achieves superior performance to the state-of-the-art methods on the four public benchmark datasets, i.e., MSRAction3D, MSRDailyActivity3D, MSRGesture3D, and MSRActionPairs3D.

  20. Human factors of flight-deck checklists: The normal checklist

    NASA Technical Reports Server (NTRS)

    Degani, Asaf; Wiener, Earl L.

    1991-01-01

    Although the aircraft checklist has long been regarded as the foundation of pilot standardization and cockpit safety, it has escaped the scrutiny of the human factors profession. The improper use, or the non-use, of the normal checklist by flight crews is often cited as the probable cause or at least a contributing factor to aircraft accidents. An attempt is made to analyze the normal checklist, its functions, format, design, length, usage, and the limitations of the humans who must interact with it. The development of the checklist from the certification of a new model to its delivery and use by the customer are discussed. The influence of the government, particularly the FAA Principle Operations Inspector, the manufacturer's philosophy, the airline's culture, and the end user, the pilot, influence the ultimate design and usage of this device. The effects of airline mergers and acquisitions on checklist usage and design are noted. In addition, the interaction between production pressures and checklist usage and checklist management are addressed. Finally, a list of design guidelines for normal checklists is provided.

  1. General anesthesia suppresses normal heart rate variability in humans

    NASA Astrophysics Data System (ADS)

    Matchett, Gerald; Wood, Philip

    2014-06-01

    The human heart normally exhibits robust beat-to-beat heart rate variability (HRV). The loss of this variability is associated with pathology, including disease states such as congestive heart failure (CHF). The effect of general anesthesia on intrinsic HRV is unknown. In this prospective, observational study we enrolled 100 human subjects having elective major surgical procedures under general anesthesia. We recorded continuous heart rate data via continuous electrocardiogram before, during, and after anesthesia, and we assessed HRV of the R-R intervals. We assessed HRV using several common metrics including Detrended Fluctuation Analysis (DFA), Multifractal Analysis, and Multiscale Entropy Analysis. Each of these analyses was done in each of the four clinical phases for each study subject over the course of 24 h: Before anesthesia, during anesthesia, early recovery, and late recovery. On average, we observed a loss of variability on the aforementioned metrics that appeared to correspond to the state of general anesthesia. Following the conclusion of anesthesia, most study subjects appeared to regain their normal HRV, although this did not occur immediately. The resumption of normal HRV was especially delayed on DFA. Qualitatively, the reduction in HRV under anesthesia appears similar to the reduction in HRV observed in CHF. These observations will need to be validated in future studies, and the broader clinical implications of these observations, if any, are unknown.

  2. Multimodality Management of Trigeminal Schwannomas.

    PubMed

    Niranjan, Ajay; Barnett, Samuel; Anand, Vijay; Agazzi, Siviero

    2016-08-01

    Patients presenting with trigeminal schwannomas require multimodality management by a skull base surgical team that can offer expertise in both transcranial and transnasal approaches as well as radiosurgical and microsurgical strategies. Improvement in neurologic symptoms, preservation of cranial nerve function, and control of mass effect are the primary goals of management for trigeminal schwannomas. Complete surgical resection is the treatment of choice but may not be possible in all cases. Radiosurgery is an option as primary management for small- to moderate-sized tumors and can be used for postoperative residuals or recurrences. Planned surgical resection followed by SRS for residual tumor is an effective option for larger trigeminal schwannomas. The endoscopic resection is an excellent approach for patients with an extradural tumor or tumors isolated to the Meckel cave. A detailed analysis of a tumor and its surroundings based on high-quality imaging can help better estimate the expected outcome from each treatment. An expert skull base team should be able to provide precise counseling for each patient's situation for selecting the best option.

  3. Rehabilitation of the trigeminal nerve

    PubMed Central

    Iro, Heinrich; Bumm, Klaus; Waldfahrer, Frank

    2005-01-01

    When it comes to restoring impaired neural function by means of surgical reconstruction, sensory nerves have always been in the role of the neglected child when compared with motor nerves. Especially in the head and neck area, with its either sensory, motor or mixed cranial nerves, an impaired sensory function can cause severe medical conditions. When performing surgery in the head and neck area, sustaining neural function must not only be highest priority for motor but also for sensory nerves. In cases with obvious neural damage to sensory nerves, an immediate neural repair, if necessary with neural interposition grafts, is desirable. Also in cases with traumatic trigeminal damage, an immediate neural repair ought to be considered, especially since reconstructive measures at a later time mostly require for interposition grafts. In terms of the trigeminal neuralgia, commonly thought to arise from neurovascular brainstem compression, a pharmaceutical treatment is considered as the state of the art in terms of conservative therapy. A neurovascular decompression of the trigeminal root can be an alternative in some cases when surgical treatment is sought after. Besides the above mentioned therapeutic options, alternative treatments are available. PMID:22073060

  4. Lysyl oxidase activity in human normal skins and postburn scars.

    PubMed

    Hayakawa, T; Hino, N; Fuyamada, H; Nagatsu, T; Aoyama, H

    1976-09-06

    Lysyl oxidase activity of human normal skins derived from the frontal thighs of 33 subjects showed large variations and the mean value was 11 455 +/- 7 172 (S.D.) cpm/g of wet weight tissue. The age of lesion affected the lysyl oxidase activity in postburn scars. Granulation tissues showed a fairly low activity; however, the activity increased sharply within 2--3 months, and reached a significantly higher value than that of normal skin. The high level of activity continued for up to 2--3 years, then gradually decreased to normal range after 5 years or so. Lysyl oxidase activity was detected only after 4 M urea treatment of tissues. Benzylamine oxidase activity also showed large variations in both normal skins and postburn scars, with mean values of: 0.128 +/- 0.077 (S.D.) and 0.145 +/- 0.090 (S.D.) mmol/g of wet weight/h, respectively. No correlation was observed between lysyl oxidase and benzylamine oxidase activities. The granulation tissues showed significantly high values of benzylamine oxidase activity in contrast to the low values of lysyl oxidase activity.

  5. Characterization of integrin receptors in normal and neoplastic human brain.

    PubMed Central

    Paulus, W.; Baur, I.; Schuppan, D.; Roggendorf, W.

    1993-01-01

    We studied the immunohistochemical expression of integrin alpha and beta chains in the normal and neoplastic human brain. Normal astrocytes expressed alpha 2, alpha 3, alpha 6, beta 1, and beta 4 chains in some areas facing major interstitial tissues, but they were consistently negative for the other integrins examined (alpha 4, alpha 5, alpha V, alpha L, alpha M, alpha X, beta 2, beta 3). Neoplastic astrocytes in vivo and in vitro showed increased expression of alpha 3 and beta 1, and some also of alpha 5, alpha V, beta 3, and beta 4. Neoexpression of alpha 4 and reduced levels of beta 4 were detected in glioblastoma vascular proliferations compared with normal endothelial cells. Oligodendroglioma, ependymoma, choroid plexus papilloma, pituitary adenoma, and meningioma cells showed the same integrin pattern as their normal counterparts. Adhesion assays using the astrocytoma cell lines U-138 MG and U-373 MG revealed strong attachment to collagen types I to VI and undulin, which was inhibited by antibodies to beta 1, but not by those to alpha 2, alpha 3, alpha 6, and alpha V. We conclude that astrocytomas show increased levels or neoexpression of various integrins and strong attachment to various extracellular matrix components, which appears to be almost exclusively mediated by beta 1-integrins. Images Figure 1 PMID:8317546

  6. Gene profile identifies zinc transporters differentially expressed in normal human organs and human pancreatic cancer.

    PubMed

    Yang, J; Zhang, Y; Cui, X; Yao, W; Yu, X; Cen, P; Hodges, S E; Fisher, W E; Brunicardi, F C; Chen, C; Yao, Q; Li, M

    2013-03-01

    Deregulated expression of zinc transporters was linked to several cancers. However, the detailed expression profile of all human zinc transporters in normal human organs and in human cancer, especially in pancreatic cancer is not available. The objectives of this study are to investigate the complete expression patterns of 14 ZIP and 10 ZnT transporters in a large number of normal human organs and in human pancreatic cancer tissues and cell lines. We examined the expression patterns of ZIP and ZnT transporters in 22 different human organs and tissues, 11 pairs of clinical human pancreatic cancer specimens and surrounding normal/benign tissues, as well as 10 established human pancreatic cancer cell lines plus normal human pancreatic ductal epithelium (HPDE) cells, using real time RT-PCR and immunohistochemistry. The results indicate that human zinc transporters have tissue specific expression patterns, and may play different roles in different organs or tissues. Almost all the ZIPs except for ZIP4, and most ZnTs were down-regulated in human pancreatic cancer tissues compared to the surrounding benign tissues. The expression patterns of individual ZIPs and ZnTs are similar among different pancreatic cancer lines. Those results and our previous studies suggest that ZIP4 is the only zinc transporter that is significantly up-regulated in human pancreatic cancer and might be the major zinc transporter that plays an important role in pancreatic cancer growth. ZIP4 might serve as a novel molecular target for pancreatic cancer diagnosis and therapy.

  7. Optical Properties of Human Cancer and Normal Cells

    NASA Astrophysics Data System (ADS)

    Sander, Christopher; Sun, Nan; Johnson, Jeffrey; Stack, Sharon; Tanner, Carol; Ruggiero, Steven

    2014-03-01

    We have investigated the optical properties of human oral and ovarian cancer and normal cells. Specifically, we have measured the absolute optical extinction for both whole cells and intra-cellular material in aqueous suspension. Measurements were conducted over a wavelength range of 250 to 1000nm with 1 nm resolution using Light Transmission Spectroscopy (LTS). This provides both the absolute extinction of materials under study and, with Mie inversion, the absolute number of particles of a given diameter as a function of diameter in the range of 1 to 3000 nm. Our preliminary studies show significant differences in both the extinction and particle size distributions associated with cancer versus normal cells, which appear to be correlated with differences in the particle size distribution in the range of ~ 50 to 250 nm.

  8. Effects of water immersion on plasma catecholamines in normal humans

    NASA Technical Reports Server (NTRS)

    Epstein, M.; Johnson, G.; Denunzio, A. G.

    1983-01-01

    An investigation was conducted in order to determine whether water immersion to the neck (NI) alters plasma catecholamines in normal humans. Eight normal subjects were studied during a seated control study (C) and during 4 hr of NI, and the levels of norepinephrine (NE) and epinephrine (E) as determined by radioenzymatic assay were measured hourly. Results show that despite the induction of a marked natriuresis and diuresis indicating significant central hypervolemia, NI failed to alter plasma NE or E levels compared with those of either C or the corresponding prestudy 1.5 hr. In addition, the diuresis and natriuresis was found to vary independently of NE. These results indicate that the response of the sympathetic nervous system to acute volume alteration may differ from the reported response to chronic volume expansion.

  9. Effects of ozone in normal human epidermal keratinocytes.

    PubMed

    McCarthy, James T; Pelle, Edward; Dong, Kelly; Brahmbhatt, Krupa; Yarosh, Dan; Pernodet, Nadine

    2013-05-01

    Ozone is a tropospheric pollutant that can form at ground level as a result of an interaction between sunlight and hydrocarbon engine emissions. As ozone is an extremely oxidative reaction product, epidermal cells are in the outer layer of defense against ozone. We exposed normal human epidermal keratinocytes (NHEK) to concentrations of ozone that have been measured in cities and assayed for its effects. Hydrogen peroxide and IL-1α levels both increased while ATP levels decreased. We found a decrease in the NAD-dependent histone deacetylase, sirtuin 3. Lastly, we found that ozone increased DNA damage as evaluated by Comet assay. Taken together, our results show increased damage to NHEK that will ultimately impair normal cellular function as a result of an environmentally relevant ozone exposure.

  10. Doublecortin expression in the normal and epileptic adult human brain.

    PubMed

    Liu, Y W J; Curtis, M A; Gibbons, H M; Mee, E W; Bergin, P S; Teoh, H H; Connor, B; Dragunow, M; Faull, R L M

    2008-12-01

    Mesial temporal lobe epilepsy (MTLE) is a neurological disorder associated with spontaneous recurrent complex partial seizures and hippocampal sclerosis. Although increased hippocampal neurogenesis has been reported in animal models of MTLE, increased neurogenesis has not been reported in the hippocampus of adult human MTLE cases. Here we showed that cells expressing doublecortin (Dcx), a microtubule-associated protein expressed in migrating neuroblasts, were present in the hippocampus and temporal cortex of the normal and MTLE adult human brain. In particular, increased numbers of Dcx-positive cells were observed in the epileptic compared with the normal temporal cortex. Importantly, 56% of Dcx-expressing cells in the epileptic temporal cortex coexpressed both the proliferative cell marker, proliferating cell nuclear antigen and early neuronal marker, TuJ1, suggesting that they may be newly generated neurons. A subpopulation of Dcx-positive cells in the epileptic temporal cortex also coexpressed the mature neuronal marker, NeuN, suggesting that epilepsy may promote the generation of new neurons in the temporal cortex. This study has identified, for the first time, a novel population of Dcx-positive cells in the adult human temporal cortex that can be upregulated by epilepsy and thus, raises the possibility that these cells may have functional significance in the pathophysiology of epilepsy.

  11. Hemodynamic aspects of normal human feto-placental (umbilical) circulation.

    PubMed

    Acharya, Ganesh; Sonesson, Sven-Erik; Flo, Kari; Räsänen, Juha; Odibo, Anthony

    2016-06-01

    Understanding the changes in normal circulatory dynamics that occur during the course of pregnancy is essential for improving our knowledge of pathophysiological mechanisms associated with feto-placental diseases. The umbilical circulation is the lifeline of the fetus, and it is accessible for noninvasive assessment. However, not all hemodynamic parameters can be reliably measured in utero using currently available technology. Experimental animal studies have been crucial in validating major concepts related to feto-placental circulatory physiology, but caution is required in directly translating the findings of such studies into humans due to species differences. Furthermore, it is important to establish normal reference ranges and take into account gestational age associated changes while interpreting the results of clinical investigation. Therefore, it is necessary to critically evaluate, synthesize and summarize the knowledge available from the studies performed on human pregnancies to be able to appropriately apply them in clinical practice. This narrative review is an attempt to present contemporary concepts on hemodynamics of feto-placental circulation based on human studies.

  12. Immortalization of human normal and NF1 neurofibroma Schwann cells.

    PubMed

    Li, Hua; Chang, Lung-Ji; Neubauer, Debbie R; Muir, David F; Wallace, Margaret R

    2016-10-01

    Neurofibromas, which are benign Schwann cell tumors, are the hallmark feature in the autosomal dominant condition neurofibromatosis 1 (NF1) and are associated with biallelic loss of NF1 gene function. There is a need for effective therapies for neurofibromas, particularly the larger, plexiform neurofibromas. Tissue culture is an important tool for research. However, it is difficult to derive enriched human Schwann cell cultures, and most enter replicative senescence after 6-10 passages, impeding cell-based research in NF1. Through exogenous expression of human telomerase reverse transcriptase and murine cyclin-dependent kinase (mCdk4), normal (NF1 wild-type), neurofibroma-derived Schwann cells heterozygous for NF1 mutation, and neurofibroma-derived Schwann cells homozygous for NF1 mutation were immortalized, including some matched samples from the same NF1 patient. Initial experiments employed retroviral vectors, while subsequent work utilized lentiviral vectors carrying these genes because of improved efficiency. Expression of both transgenes was required for immortalization. Molecular and immunohistochemical analysis indicated that these cell lines are of Schwann cell lineage and have a range of phenotypes, many of which are consistent with their primary cultures. This is the first report of immortalization and detailed characterization of multiple human NF1 normal nerve and neurofibroma-derived Schwann cell lines, which will be highly useful research tools to study NF1 and other Schwann tumor biology and conditions.

  13. A quantitative transcriptome reference map of the normal human brain.

    PubMed

    Caracausi, Maria; Vitale, Lorenza; Pelleri, Maria Chiara; Piovesan, Allison; Bruno, Samantha; Strippoli, Pierluigi

    2014-10-01

    We performed an innovative systematic meta-analysis of 60 gene expression profiles of whole normal human brain, to provide a quantitative transcriptome reference map of it, i.e. a reference typical value of expression for each of the 39,250 known, mapped and 26,026 uncharacterized (unmapped) transcripts. To this aim, we used the software named Transcriptome Mapper (TRAM), which is able to generate transcriptome maps based on gene expression data from multiple sources. We also analyzed differential expression by comparing the brain transcriptome with those derived from human foetal brain gene expression, from a pool of human tissues (except the brain) and from the two normal human brain regions cerebellum and cerebral cortex, which are two of the main regions severely affected when cognitive impairment occurs, as happens in the case of trisomy 21. Data were downloaded from microarray databases, processed and analyzed using TRAM software and validated in vitro by assaying gene expression through several magnitude orders by 'real-time' reverse transcription polymerase chain reaction (RT-PCR). The excellent agreement between in silico and experimental data suggested that our transcriptome maps may be a useful quantitative reference benchmark for gene expression studies related to the human brain. Furthermore, our analysis yielded biological insights about those genes which have an intrinsic over-/under-expression in the brain, in addition offering a basis for the regional analysis of gene expression. This could be useful for the study of chromosomal alterations associated to cognitive impairment, such as trisomy 21, the most common genetic cause of intellectual disability.

  14. Regulation of p53 during senescence in normal human keratinocytes

    PubMed Central

    Kim, Reuben H; Kang, Mo K; Kim, Terresa; Yang, Paul; Bae, Susan; Williams, Drake W; Phung, Samantha; Shin, Ki-Hyuk; Hong, Christine; Park, No-Hee

    2015-01-01

    p53, the guardian of the genome, is a tumor suppressor protein and critical for the genomic integrity of the cells. Many studies have shown that intracellular level of p53 is enhanced during replicative senescence in normal fibroblasts, and the enhanced level of p53 is viewed as the cause of senescence. Here, we report that, unlike in normal fibroblasts, the level of intracellular p53 reduces during replicative senescence and oncogene-induced senescence (OIS) in normal human keratinocytes (NHKs). We found that the intracellular p53 level was also decreased in age-dependent manner in normal human epithelial tissues. Senescent NHKs exhibited an enhanced level of p16INK4A, induced G2 cell cycle arrest, and lowered the p53 expression and transactivation activity. We found that low level of p53 in senescent NHKs was due to reduced transcription of p53. The methylation status at the p53 promoter was not altered during senescence, but senescent NHKs exhibited notably lower level of acetylated histone 3 (H3) at the p53 promoter in comparison with rapidly proliferating cells. Moreover, p53 knockdown in rapidly proliferating NHKs resulted in the disruption of fidelity in repaired DNA. Taken together, our study demonstrates that p53 level is diminished during replicative senescence and OIS and that such diminution is associated with H3 deacetylation at the p53 promoter. The reduced intracellular p53 level in keratinocytes of the elderly could be a contributing factor for more frequent development of epithelial cancer in the elderly because of the loss of genomic integrity of cells. PMID:26138448

  15. Cationic channels in normal and dystrophic human myotubes.

    PubMed

    Vandebrouck, C; Duport, G; Cognard, C; Raymond, G

    2001-01-01

    Human skeletal muscle cells obtained from normal and Duchenne muscular dystrophy patients were cocultured with explants of rat dorsal root ganglions. Single-channel recordings were performed with the cell-attached configuration of the patch-clamp technique and negative pressure was applied via the patch-pipette in order to mechanically stimulate the membrane patch. Inward elementary current activity was recorded under control or negative pressure conditions. Its occurrence and mean open probability were higher in Duchenne muscular dystrophy. Amplitude histograms reveal that these channels have a small unitary conductance of around 10 pS in 110 mM Ca2+ and could be inhibited in a dose-dependent manner by gadolinium. Results show that the membrane stress favoured calcium permeation through these channels. Taken together these data provide arguments for the involvement of such channels in calcium overload previously observed in cocultured dystrophic human (Duchenne muscular dystrophy) muscle cells.

  16. Divergent viral presentation among human tumors and adjacent normal tissues

    PubMed Central

    Cao, Song; Wendl, Michael C.; Wyczalkowski, Matthew A.; Wylie, Kristine; Ye, Kai; Jayasinghe, Reyka; Xie, Mingchao; Wu, Song; Niu, Beifang; Grubb, Robert; Johnson, Kimberly J.; Gay, Hiram; Chen, Ken; Rader, Janet S.; Dipersio, John F.; Chen, Feng; Ding, Li

    2016-01-01

    We applied a newly developed bioinformatics system called VirusScan to investigate the viral basis of 6,813 human tumors and 559 adjacent normal samples across 23 cancer types and identified 505 virus positive samples with distinctive, organ system- and cancer type-specific distributions. We found that herpes viruses (e.g., subtypes HHV4, HHV5, and HHV6) that are highly prevalent across cancers of the digestive tract showed significantly higher abundances in tumor versus adjacent normal samples, supporting their association with these cancers. We also found three HPV16-positive samples in brain lower grade glioma (LGG). Further, recurrent HBV integration at the KMT2B locus is present in three liver tumors, but absent in their matched adjacent normal samples, indicating that viral integration induced host driver genetic alterations are required on top of viral oncogene expression for initiation and progression of liver hepatocellular carcinoma. Notably, viral integrations were found in many genes, including novel recurrent HPV integrations at PTPN13 in cervical cancer. Finally, we observed a set of HHV4 and HBV variants strongly associated with ethnic groups, likely due to viral sequence evolution under environmental influences. These findings provide important new insights into viral roles of tumor initiation and progression and potential new therapeutic targets. PMID:27339696

  17. Terahertz spectroscopic investigation of human gastric normal and tumor tissues

    NASA Astrophysics Data System (ADS)

    Hou, Dibo; Li, Xian; Cai, Jinhui; Ma, Yehao; Kang, Xusheng; Huang, Pingjie; Zhang, Guangxin

    2014-09-01

    Human dehydrated normal and cancerous gastric tissues were measured using transmission time-domain terahertz spectroscopy. Based on the obtained terahertz absorption spectra, the contrasts between the two kinds of tissue were investigated and techniques for automatic identification of cancerous tissue were studied. Distinctive differences were demonstrated in both the shape and amplitude of the absorption spectra between normal and tumor tissue. Additionally, some spectral features in the range of 0.2~0.5 THz and 1~1.5 THz were revealed for all cancerous gastric tissues. To systematically achieve the identification of gastric cancer, principal component analysis combined with t-test was used to extract valuable information indicating the best distinction between the two types. Two clustering approaches, K-means and support vector machine (SVM), were then performed to classify the processed terahertz data into normal and cancerous groups. SVM presented a satisfactory result with less false classification cases. The results of this study implicate the potential of the terahertz technique to detect gastric cancer. The applied data analysis methodology provides a suggestion for automatic discrimination of terahertz spectra in other applications.

  18. Disposition of human fibrinopeptide A in normal and nephrectomized rabbits

    SciTech Connect

    Harenberg, J.; Stehle, G.; Waibel, S.; Hermann, H.J.; Eisenhut, M.; Zimmermann, R.

    1983-10-01

    The distribution, elimination, and metabolism of human fibrinopeptide A (FPA) were studied in normal and nephrectomized rabbits. The activity of /sup 125/I-labeled desamino-tyrosyl human FPA (DAT-FPA) was followed over 4 hours after i.v. administration. Results show that in normal rabbits (n . 10) DAT-FPA is eliminated from plasma in four phases with half-lives of 30 sec, 3.5 min, 15 min, and 90 min. The distribution of /sup 123/I-labeled DAT-FPA in plasma was determined in 15 control rabbits with scintigraphy over 2 hours. DAT-FPA was distributed primarily in the cardiovascular system, liver, and kidneys. In some animals minimal radioactivity was detected over the gall bladder. Radioactivity accumulated rapidly in the urinary bladder, approximately 50% being recorded after 15 min and 90% after 120 min. In the heart area radioactivity decreased with half-lives of 25 sec, 7.5 min, 25 min, and 180 min. Nephrectomized rabbits had similar initial fast distribution of DAT-FPA after administration of /sup 125/I-labeled (n . 10) and /sup 123/I-labeled peptide (n . 10). The estimated half-life of the slow component was in the order of several hours. The results of the scintigraphic and gel chromatographic studies show that FPA is primarily excreted in the urine. Previously reported half-lives of FPA reflect distribution rather than steady state conditions.

  19. p120 GAP requirement in normal and malignant human hematopoiesis

    PubMed Central

    1993-01-01

    There is evidence to suggest that the p120 GAP (GAP), originally described as an inhibitor of p21ras, may also serve as a downstream effector of ras-regulated signal transduction. To determine whether GAP expression is required for the growth of human normal and leukemic hematopoietic cells, we used GAP antisense oligodeoxynucleotides to inhibit it and analyzed the effects of this inhibition on the colony- forming ability of nonadherent, T lymphocyte-depleted mononuclear cells and of highly purified progenitors (CD34+ MNC) obtained from the bone marrow and peripheral blood of healthy volunteers or chronic myeloid leukemia (CML, bcr-abl-positive) patients. The acute myelogenous leukemia cell line MO7, the Philadelphia BV173 cell line, and the acute promyelocytic leukemia NB4 and HL-60 cell lines were similarly examined. GAP antisense treatment inhibited colony formation from normal myelo-, erythro-, and megakaryopoietic progenitor cells as well as from CML progenitor cells. Proliferation of MO7 (growth factor- dependent) and BV173 (bcr-abl-dependent) cells, but not that of NB4 and HL-60 (growth factor-independent) cells, was also inhibited, even though a specific downregulation of GAP was observed in each cell line, as analyzed by either or both mRNA and protein expression. Stimulation of MO7 cells with hematopoietic growth factors increased the expression of GAP as well as the levels of active GTP-bound p21ras. Stimulation of GAP expression was inhibited upon GAP antisense treatment. These data indicate that p120 GAP is involved in human normal and leukemic hemopoiesis and strongly suggest that GAP is not only a p21ras inhibitor (signal terminator), but also a positive signal transducer. PMID:8245773

  20. Microsurgical anatomy of the trigeminal nerve.

    PubMed

    Joo, Wonil; Yoshioka, Fumitaka; Funaki, Takeshi; Mizokami, Koji; Rhoton, Albert L

    2014-01-01

    The objective of this study is to review surgical anatomy of the trigeminal nerve. We also demonstrate some pictures involving the trigeminal nerve and its surrounding connective and neurovascular structures. Ten adult cadaveric heads were studied, using a magnification ranging from 3× to 40×, after perfusion of the arteries and veins with colored latex. The trigeminal nerve is the largest and most complex of the cranial nerves. It serves as a major conduit of sensory input from the face and provides motor innervation to the muscles of mastication. Because of its size and complexity, it is essential to have thorough knowledge of the nerve before diagnoses and treatment of the pathologic processes in the orofacial, temporomandibular, infratemporal, and pterygopalatine areas. The trigeminal nerve is encountered with imaging or surgery of the skull base surgery. Thus, a comprehensive knowledge of the anatomy of the trigeminal nerve is crucial for performing the surgical procedures without significant complication.

  1. Transient Receptor Potential Channels Encode Volatile Chemicals Sensed by Rat Trigeminal Ganglion Neurons

    PubMed Central

    Schöbel, Nicole; Beltrán, Leopoldo; Wetzel, Christian Horst; Hatt, Hanns

    2013-01-01

    Primary sensory afferents of the dorsal root and trigeminal ganglia constantly transmit sensory information depicting the individual’s physical and chemical environment to higher brain regions. Beyond the typical trigeminal stimuli (e.g. irritants), environmental stimuli comprise a plethora of volatile chemicals with olfactory components (odorants). In spite of a complete loss of their sense of smell, anosmic patients may retain the ability to roughly discriminate between different volatile compounds. While the detailed mechanisms remain elusive, sensory structures belonging to the trigeminal system seem to be responsible for this phenomenon. In order to gain a better understanding of the mechanisms underlying the activation of the trigeminal system by volatile chemicals, we investigated odorant-induced membrane potential changes in cultured rat trigeminal neurons induced by the odorants vanillin, heliotropyl acetone, helional, and geraniol. We observed the dose-dependent depolarization of trigeminal neurons upon application of these substances occurring in a stimulus-specific manner and could show that distinct neuronal populations respond to different odorants. Using specific antagonists, we found evidence that TRPA1, TRPM8, and/or TRPV1 contribute to the activation. In order to further test this hypothesis, we used recombinantly expressed rat and human variants of these channels to investigate whether they are indeed activated by the odorants tested. We additionally found that the odorants dose-dependently inhibit two-pore potassium channels TASK1 and TASK3 heterologously expressed In Xenopus laevis oocytes. We suggest that the capability of various odorants to activate different TRP channels and to inhibit potassium channels causes neuronal depolarization and activation of distinct subpopulations of trigeminal sensory neurons, forming the basis for a specific representation of volatile chemicals in the trigeminal ganglia. PMID:24205061

  2. Transient receptor potential channels encode volatile chemicals sensed by rat trigeminal ganglion neurons.

    PubMed

    Lübbert, Matthias; Kyereme, Jessica; Schöbel, Nicole; Beltrán, Leopoldo; Wetzel, Christian Horst; Hatt, Hanns

    2013-01-01

    Primary sensory afferents of the dorsal root and trigeminal ganglia constantly transmit sensory information depicting the individual's physical and chemical environment to higher brain regions. Beyond the typical trigeminal stimuli (e.g. irritants), environmental stimuli comprise a plethora of volatile chemicals with olfactory components (odorants). In spite of a complete loss of their sense of smell, anosmic patients may retain the ability to roughly discriminate between different volatile compounds. While the detailed mechanisms remain elusive, sensory structures belonging to the trigeminal system seem to be responsible for this phenomenon. In order to gain a better understanding of the mechanisms underlying the activation of the trigeminal system by volatile chemicals, we investigated odorant-induced membrane potential changes in cultured rat trigeminal neurons induced by the odorants vanillin, heliotropyl acetone, helional, and geraniol. We observed the dose-dependent depolarization of trigeminal neurons upon application of these substances occurring in a stimulus-specific manner and could show that distinct neuronal populations respond to different odorants. Using specific antagonists, we found evidence that TRPA1, TRPM8, and/or TRPV1 contribute to the activation. In order to further test this hypothesis, we used recombinantly expressed rat and human variants of these channels to investigate whether they are indeed activated by the odorants tested. We additionally found that the odorants dose-dependently inhibit two-pore potassium channels TASK1 and TASK3 heterologously expressed In Xenopus laevis oocytes. We suggest that the capability of various odorants to activate different TRP channels and to inhibit potassium channels causes neuronal depolarization and activation of distinct subpopulations of trigeminal sensory neurons, forming the basis for a specific representation of volatile chemicals in the trigeminal ganglia.

  3. Human cancers overexpress genes that are specific to a variety of normal human tissues

    PubMed Central

    Lotem, Joseph; Netanely, Dvir; Domany, Eytan; Sachs, Leo

    2005-01-01

    We have analyzed gene expression data from three different kinds of samples: normal human tissues, human cancer cell lines, and leukemic cells from lymphoid and myeloid leukemia pediatric patients. We have searched for genes that are overexpressed in human cancer and also show specific patterns of tissue-dependent expression in normal tissues. Using the expression data of the normal tissues, we identified 4,346 genes with a high variability of expression and clustered these genes according to their relative expression level. Of 91 stable clusters obtained, 24 clusters included genes preferentially expressed either only in hematopoietic tissues or in hematopoietic and one to two other tissues; 28 clusters included genes preferentially expressed in various nonhematopoietic tissues such as neuronal, testis, liver, kidney, muscle, lung, pancreas, and placenta. Analysis of the expression levels of these two groups of genes in the human cancer cell lines and leukemias identified genes that were highly expressed in cancer cells but not in their normal counterparts and, thus, were overexpressed in the cancers. The different cancer cell lines and leukemias varied in the number and identity of these overexpressed genes. The results indicate that many genes that are overexpressed in human cancer cells are specific to a variety of normal tissues, including normal tissues other than those from which the cancer originated. It is suggested that this general property of cancer cells plays a major role in determining the behavior of the cancers, including their metastatic potential. PMID:16339305

  4. Differential Intracochlear Sound Pressure Measurements in Normal Human Temporal Bones

    NASA Astrophysics Data System (ADS)

    Nakajima, Hideko Heidi; Dong, Wei; Olson, Elizabeth S.; Merchant, Saumil N.; Ravicz, Michael E.; Rosowski, John J.

    2009-02-01

    We present the first simultaneous sound pressure measurements in scala vestibuli and scala tympani of the cochlea in human cadaveric temporal bones. Micro-scale fiberoptic pressure sensors enabled the study of differential sound pressure at the cochlear base. This differential pressure is the input to the cochlear partition, driving cochlear waves and auditory transduction. Results showed that: pressure of scala vestibuli was much greater than scala tympani except at low and high frequencies where scala tympani pressure affects the input to the cochlea; the differential pressure proved to be an excellent measure of normal ossicular transduction of sound (shown to decrease 30-50 dB with ossicular disarticulation, whereas the individual scala pressures were significantly affected by non-ossicular conduction of sound at high frequencies); the middle-ear gain and differential pressure were generally bandpass in frequency dependence; and the middle-ear delay in the human was over twice that of the gerbil. Concurrent stapes velocity measurements allowed determination of the differential impedance across the partition and round-window impedance. The differential impedance was generally resistive, while the round-window impedance was consistent with a compliance in conjunction with distributed inertia and damping. Our techniques can be used to study inner-ear conductive pathologies (e.g., semicircular dehiscence), as well as non-ossicular cochlear stimulation (e.g., round-window stimulation) - situations that cannot be completely quantified by measurements of stapes velocity or scala-vestibuli pressure by themselves.

  5. Complement Interaction with Trypanosomatid Promastigotes in Normal Human Serum

    PubMed Central

    Domínguez, Mercedes; Moreno, Inmaculada; López-Trascasa, Margarita; Toraño, Alfredo

    2002-01-01

    In normal human serum (NHS), axenic promastigotes of Crithidia, Phytomonas, and Leishmania trigger complement activation, and from 1.2 to 1.8 × 105 C3 molecules are deposited per promastigote within 2.5 min. In Leishmania, promastigote C3 binding capacity remains constant during in vitro metacyclogenesis. C3 deposition on promastigotes activated through the classical complement pathway reaches a 50% maximum after ∼50 s, and represents >85% of total C3 bound. In C1q- and C2-deficient human sera, promastigotes cannot activate the classical pathway (CP) unless purified C1q or C2 factors, respectively, are supplemented, demonstrating a requirement for CP factor in promastigote C3 opsonization. NHS depleted of natural anti-Leishmania antibodies cannot trigger promastigote CP activation, but IgM addition restores C3 binding. Furthermore, Leishmania binds natural antibodies in ethylenediaminetetracetic acid (EDTA)-treated NHS; after EDTA removal, promastigote-bound IgM triggers C3 deposition in natural antibody-depleted NHS. Serum collectins and pentraxins thus do not participate significantly in NHS promastigote C3 opsonization. Real-time kinetic analysis of promastigote CP-mediated lysis indicates that between 85–95% of parasites are killed within 2.5 min of serum contact. These data indicate that successful Leishmania infection in man must immediately follow promastigote transmission, and that Leishmania evasion strategies are shaped by the selective pressure exerted by complement. PMID:11854358

  6. [Update on the management of trigeminal neuralgia].

    PubMed

    Alcántara Montero, A; Sánchez Carnerero, C I

    2016-01-01

    Trigeminal neuralgia is one of the most severe facial pain syndromes. The annual incidence varies between 4-13% and has a significant effect on patient quality of life. The initial treatment of trigeminal neuralgia is pharmacological, and although other drugs have demonstrated efficacy, albeit in more limited form, carbamazepine is the only drug with sufficient level of evidence. When medical treatment fails, surgery should be considered and can opt for open surgery or minimally invasive percutaneous techniques. This paper reviews the medical and surgical therapeutic options for the treatment of trigeminal neuralgia, based on current available evidence.

  7. Physiological brainstem mechanisms of trigeminal nociception: An fMRI study at 3T.

    PubMed

    Schulte, Laura H; Sprenger, Christian; May, Arne

    2016-01-01

    The brainstem is a major site of processing and modulation of nociceptive input and plays a key role in the pathophysiology of various headache disorders. However, human imaging studies on brainstem function following trigeminal nociceptive stimulation are scarce as brainstem specific imaging approaches have to address multiple challenges such as magnetic field inhomogeneities and an enhanced level of physiological noise. In this study we used a viable protocol for brainstem fMRI of standardized trigeminal nociceptive stimulation to achieve detailed insight into physiological brainstem mechanisms of trigeminal nociception. We conducted a study of 21 healthy participants using a nociceptive ammonia stimulation of the left nasal mucosa with an optimized MR acquisition protocol for high resolution brainstem echoplanar imaging in combination with two different noise correction techniques. Significant BOLD responses to noxious ammonia stimulation were observed in areas typically involved in trigeminal nociceptive processing such as the spinal trigeminal nuclei (sTN), thalamus, secondary somatosensory cortex, insular cortex and cerebellum as well as in a pain modulating network including the periaqueductal gray area, hypothalamus (HT), locus coeruleus and cuneiform nucleus (CNF). Activations of the left CNF were positively correlated with pain intensity ratings. Employing psychophysiological interaction (PPI) analysis we found enhanced functional connectivity of the sTN with the contralateral sTN and HT following trigeminal nociception. We also observed enhanced functional connectivity of the CNF with the RVM during painful stimulation thus implying an important role of these two brainstem regions in central pain processing. The chosen approach to study trigeminal nociception with high-resolution fMRI offers new insight into human pain processing and might thus lead to a better understanding of headache pathophysiology.

  8. Influences of smoking and caffeine consumption on trigeminal pain processing

    PubMed Central

    2014-01-01

    Background Many human and animal studies have shown the influence of nicotine and caffeine on pain perception and processing. This study aims to investigate whether smoking or caffeine consumption influences trigeminal pain processing. Methods Sixty healthy subjects were investigated using simultaneous recordings of the nociceptive blink reflex (nBR) and pain related evoked potentials (PREP) following nociceptive electrical stimulation on both sides of the forehead (V1). Thirty subjects were investigated before and after smoking a cigarette, as well as before and after taking a tablet of 400 mg caffeine. Results After smoking PREP showed decreased N2 and P2 latencies indicating central facilitation at supraspinal (thalamic or cortical) level. PREP amplitudes were not changed. NBR showed a decreased area under the curve (AUC) indicating central inhibition at brainstem level. After caffeine intake no significant changes were observed comparing nBR and PREP results before consumption. Conclusions Smoking influences trigeminal pain processing on supraspinal and brainstem level. In the investigated setting, caffeine consumption does not significantly alter trigeminal pain processing. This observation might help in the further understanding of the pathophysiology of pain disorders that are associated with excessive smoking habits such as cluster headache. Previous smoking has to be taken into account when performing electrophysiological studies to avoid bias of study results. PMID:24928141

  9. A quantitative transcriptome reference map of the normal human hippocampus.

    PubMed

    Caracausi, Maria; Rigon, Vania; Piovesan, Allison; Strippoli, Pierluigi; Vitale, Lorenza; Pelleri, Maria Chiara

    2016-01-01

    We performed an innovative systematic meta-analysis of 41 gene expression profiles of normal human hippocampus to provide a quantitative transcriptome reference map of it, i.e. a reference typical value of expression for each of the 30,739 known mapped and the 16,258 uncharacterized (unmapped) transcripts. For this aim, we used the software called TRAM (Transcriptome Mapper), which is able to generate transcriptome maps based on gene expression data from multiple sources. We also analyzed differential expression by comparing the hippocampus with the whole brain transcriptome map to identify a typical expression pattern of this subregion compared with the whole organ. Finally, due to the fact that the hippocampus is one of the main brain region to be severely affected in trisomy 21 (the best known genetic cause of intellectual disability), a particular attention was paid to the expression of chromosome 21 (chr21) genes. Data were downloaded from microarray databases, processed, and analyzed using TRAM software. Among the main findings, the most over-expressed loci in the hippocampus are the expressed sequence tag cluster Hs.732685 and the member of the calmodulin gene family CALM2. The tubulin folding cofactor B (TBCB) gene is the best gene at behaving like a housekeeping gene. The hippocampus vs. the whole brain differential transcriptome map shows the over-expression of LINC00114, a long non-coding RNA mapped on chr21. The hippocampus transcriptome map was validated in vitro by assaying gene expression through several magnitude orders by "Real-Time" reverse transcription polymerase chain reaction (RT-PCR). The highly significant agreement between in silico and experimental data suggested that our transcriptome map may be a useful quantitative reference benchmark for gene expression studies related to human hippocampus. Furthermore, our analysis yielded biological insights about those genes that have an intrinsic over-/under-expression in the hippocampus.

  10. Characterizing the normal proteome of human ciliary body

    PubMed Central

    2013-01-01

    Background The ciliary body is the circumferential muscular tissue located just behind the iris in the anterior chamber of the eye. It plays a pivotal role in the production of aqueous humor, maintenance of the lens zonules and accommodation by changing the shape of the crystalline lens. The ciliary body is the major target of drugs against glaucoma as its inhibition leads to a drop in intraocular pressure. A molecular study of the ciliary body could provide a better understanding about the pathophysiological processes that occur in glaucoma. Thus far, no large-scale proteomic investigation has been reported for the human ciliary body. Results In this study, we have carried out an in-depth LC-MS/MS-based proteomic analysis of normal human ciliary body and have identified 2,815 proteins. We identified a number of proteins that were previously not described in the ciliary body including importin 5 (IPO5), atlastin-2 (ATL2), B-cell receptor associated protein 29 (BCAP29), basigin (BSG), calpain-1 (CAPN1), copine 6 (CPNE6), fibulin 1 (FBLN1) and galectin 1 (LGALS1). We compared the plasma proteome with the ciliary body proteome and found that the large majority of proteins in the ciliary body were also detectable in the plasma while 896 proteins were unique to the ciliary body. We also classified proteins using pathway enrichment analysis and found most of proteins associated with ubiquitin pathway, EIF2 signaling, glycolysis and gluconeogenesis. Conclusions More than 95% of the identified proteins have not been previously described in the ciliary body proteome. This is the largest catalogue of proteins reported thus far in the ciliary body that should provide new insights into our understanding of the factors involved in maintaining the secretion of aqueous humor. The identification of these proteins will aid in understanding various eye diseases of the anterior segment such as glaucoma and presbyopia. PMID:23914977

  11. Neuropeptides of human thymus in normal and pathological conditions.

    PubMed

    Mignini, F; Sabbatini, M; D'Andrea, V; Cavallotti, C

    2011-05-01

    Human thymus of healthy subjects and patients affected by thymoma-associated Myastenia Gravis were studied in order to visualize and compare the morphological distributive pattern of four neuropeptides: vasoactive intestinal peptide, substance P, neuropeptide Y, and neurotensin. Based on our observations, we formulated hypotheses on their relations in neuro-immunomodulation under physiological and pathophysiological conditions. Immuno-histochemical staining for neuropeptides was performed and morphological and morphometrical analyses were conducted on healthy and diseased thymus. In normal thymus, a specific distributive pattern was observed for the several neuropeptide-positive nerves in different thymus lobular zones. In particular substance P-positive fibers were observed in subcapsular zone, specifically located into parenchyma, where they represent the almost total amount of fibers; neurotensin-positive fibers were observed primarily located in parenchyma than perivascular site of several thymus lobular zones, and more abundant the cortico-medullary and medullary zones. Instead VIP- and NPY-positive fibers were widely distributed in perivascular and parenchymal sites of several thymus lobular zones. In thymoma, the distribution of neuropeptide-positive fibers was quantitatively reduced, while cells immunopositive to VIP and substance P were quantitatively increased and dispersed. Observation of the perivascular and parenchymal distribution of the analyzed neuropeptides suggests evidence that a regulatory function is performed by nerves and cells that secrete neuropeptide into the thymus. The alteration of neuropeptide patterns in thymoma suggests that these neurotransmitters play a role in autoimmune diseases such as Myastenia Gravis.

  12. Accelerated aging syndromes, are they relevant to normal human aging?

    PubMed

    Dreesen, Oliver; Stewart, Colin L

    2011-09-01

    Hutchinson-Gilford Progeria (HGPS) and Werner syndromes are diseases that clinically resemble some aspects of accelerated aging. HGPS is caused by mutations in theLMNA gene resulting in post-translational processing defects that trigger Progeria in children. Werner syndrome, arising from mutations in the WRN helicase gene, causes premature aging in young adults. What are the molecular mechanism(s) underlying these disorders and what aspects of the diseases resemble physiological human aging? Much of what we know stems from the study of patient derived fibroblasts with both mutations resulting in increased DNA damage, primarily at telomeres. However, in vivo patients with Werner's develop arteriosclerosis, among other pathologies. In HGPS patients, including iPS derived cells from HGPS patients, as well as some mouse models for Progeria, vascular smooth muscle (VSM) appears to be among the most severely affected tissues. Defective Lamin processing, associated with DNA damage, is present in VSM from old individuals, indicating processing defects may be a factor in normal aging. Whether persistent DNA damage, particularly at telomeres, is the root cause for these pathologies remains to be established, since not all progeroid Lmna mutations result in DNA damage and genome instability.

  13. 7Li NMR study of normal human erythrocytes

    NASA Astrophysics Data System (ADS)

    Pettegrew, J. W.; Post, J. F. M.; Panchalingam, K.; Withers, G.; Woessner, D. E.

    The biological action of lithium is of great interest because of the therapeutic efficacy of the cation in manic-depressive illness. To investigate possible molecular interactions of lithium, 7Li NMR studies were conducted on normal human erythrocytes which had been incubated with lithium chloride. The uptake of lithium ions was followed by 7Li NMR, using a dysprosium, tripolyphosphate shift reagent. Lithium uptake followed single-exponential kinetics with a time constant of 14.7 h. The intracellular lithium relaxation times were T 1 ⋍ 5 s and T 2 ⋍ 0.15 s, which implies a lengthening of the lithium correlation time. It was found that lithium does not interact significantly with hemoglobin, the erythrocyte membrane, or artificial phospholipid membranes. Based on measurements of lithium T1 and T2 in concentrated agar gels, the large difference between T1 and T2 for intracellular lithium ions may be due to diffusion of the hydrated lithium ion through heterogeneous electrostatic field gradients created by the erythrocyte membrane-associated cytoskeletal network. Lithium binding to the membrane-associated cytoskeleton, however, cannot be ruled out. Because of the large differences between T1 and T2 of intracellular lithium ions, 1Li NMR may be a sensitive and promising noninvasive method to probe the intracellular environment.

  14. Effective Management of Trigeminal Neuralgia by Neurostimulation

    PubMed Central

    Abd-Elsayed, Alaa A.; Grandhi, Ravi; Sachdeva, Harsh

    2015-01-01

    Background Treatment of trigeminal neuralgia can be challenging for many physicians; patients who do not respond to conventional treatments and traditional surgical approaches often continue to suffer with pain. The peripheral nerve stimulator (PNS) has been used to treat many chronic pain conditions, but few reports exist about its use to treat trigeminal neuralgia. Case Report We present the case of a patient with trigeminal neuralgia resistant to conventional techniques of pain management. Conservative pain management was attempted but was ineffective. As a result, a PNS was placed with minimally invasive surgery. Pain scores were recorded before and after the procedure, and the patient reported complete resolution of her pain. Conclusion PNS implantation can be a safe and effective method to treat trigeminal neuralgia. More research is needed to define its mechanism of action. PMID:26130986

  15. Atypical Trigeminal Neuralgia Secondary to Meningioma

    PubMed Central

    Niwant, Premeshwar; Motwani, Mukta; Naik, Sushil

    2015-01-01

    Trigeminal neuralgia is a disorder of the fifth cranial nerve that causes episodes of intense, stabbing, electric shock-like pain that lasts from few seconds to few minutes in the areas of the face where the branches of the nerve are distributed. More than one nerve branch can be affected by the disorder. We report an unusual case of trigeminal neuralgia affecting right side of face presenting atypical features of neuralgia and not responding to the usual course of treatment. The magnetic resonance imaging study of brain revealed a large extra-axial mass involving right cerebellopontine angle region causing moderate pressure effect on trigeminal nerve and brain stem. The aim of this case report is to show a tumor of cerebellopontine angle, presenting clinically as atypical trigeminal neuralgia. PMID:26664753

  16. Trigemino-cardiac reflex during microvascular trigeminal decompression in cases of trigeminal neuralgia.

    PubMed

    Schaller, Bernhard

    2005-01-01

    The trigemino-cardiac reflex (TCR) is a well-recognized phenomenon consisting of bradycardia, arterial hypotension, apnea, and gastric hypermotility during ocular surgery or other manipulations in and around the orbit. Thus far, it could bee shown that central stimulation of the trigeminal nerve during transsphenoidal surgery and surgery for tumors in the cerebellopontine angle can lead to TCR. In cases of microvascular trigeminal decompression for trigeminal neuralgia, no data of the possible occurrence of TCR are available. TCR was defined as a drop in mean arterial blood pressure (MABP) and the heart rate (HR) of more than 20% to the baseline values before the stimulus and coinciding with the manipulation of the trigeminal nerve. Electronic anesthetic recorded perioperative HR and MABP values were reviewed retrospectively in 28 patients who received microvascular trigeminal decompression in cases of trigeminal neuralgia and were divided into two subgroups on the basis of occurrence of TCR during surgery. Of the 28 patients, 5 (18%) showed evidence of TCR during manipulation at the trigeminal radix by separation from microvascular structures. Their HR fell 46% and their MABP 57% during operative procedures near the trigeminal nerve as compared with levels immediately before the stimulus. After cessation of manipulation, HR and MABP returned (spontaneously) to levels before the stimulus. Risk factors of TCR were compared with results from the literature. In conclusion, the present results give evidence of TCR during manipulation of the central part of the trigeminal nerve during microvascular trigeminal decompression in cases of trigeminal neuralgia under a standardized anesthetic protocol.

  17. Direct action and modulating effect of (+)- and (-)-nicotine on ion channels expressed in trigeminal sensory neurons.

    PubMed

    Schreiner, Benjamin S P; Lehmann, Ramona; Thiel, Ulrike; Ziemba, Paul M; Beltrán, Leopoldo R; Sherkheli, Muhammad A; Jeanbourquin, Philippe; Hugi, Alain; Werner, Markus; Gisselmann, Günter; Hatt, Hanns

    2014-04-05

    Nicotine sensory perception is generally thought to be mediated by nicotinic acetylcholine (nACh) receptors. However, recent data strongly support the idea that other receptors (e.g., transient receptor potential A1 channel, TRPA1) and other pathways contribute to the detection mechanisms underlying the olfactory and trigeminal cell response to nicotine flavor. This is in accordance with the reported ability of humans to discriminate between (+)- and (-)- nicotine enantiomers. To get a more detailed understanding of the molecular and cellular basis underlying the sensory perception of nicotine, we studied the activity of (+)- and (-)-nicotine on cultured murine trigeminal sensory neurons and on a range of heterologously expressed receptors. The human TRPA1 channel is activated by (-)-nicotine. In this work, we show that (+)-nicotine is also an activator of this channel. Pharmacological experiments using nicotinic acetylcholine receptors and transient receptor potential blockers revealed that trigeminal neurons express one or more unidentified receptors that are sensitive to (+)- and/or (-)-nicotine. Results also indicate that the presence of extracellular calcium ions is required to elicit trigeminal neuron responses to (+)- and (-)-nicotine. Results also show that both (+)-nicotine and (-)-nicotine can block 5-hydroxytryptamine type 3 (5-HT3) receptor-mediated responses in recombinant expression systems and in cultured trigeminal neurons expressing 5-HT3 receptors. Our investigations broaden the spectra of receptors that are targets for nicotine enantiomers and give new insights into the physiological role of nicotine.

  18. Clinical iron deficiency disturbs normal human responses to hypoxia

    PubMed Central

    Frise, Matthew C.; Cheng, Hung-Yuan; Nickol, Annabel H.; Curtis, M. Kate; Pollard, Karen A.; Roberts, David J.; Ratcliffe, Peter J.; Dorrington, Keith L.; Robbins, Peter A.

    2016-01-01

    BACKGROUND. Iron bioavailability has been identified as a factor that influences cellular hypoxia sensing, putatively via an action on the hypoxia-inducible factor (HIF) pathway. We therefore hypothesized that clinical iron deficiency would disturb integrated human responses to hypoxia. METHODS. We performed a prospective, controlled, observational study of the effects of iron status on hypoxic pulmonary hypertension. Individuals with absolute iron deficiency (ID) and an iron-replete (IR) control group were exposed to two 6-hour periods of isocapnic hypoxia. The second hypoxic exposure was preceded by i.v. infusion of iron. Pulmonary artery systolic pressure (PASP) was serially assessed with Doppler echocardiography. RESULTS. Thirteen ID individuals completed the study and were age- and sex-matched with controls. PASP did not differ by group or study day before each hypoxic exposure. During the first 6-hour hypoxic exposure, the rise in PASP was 6.2 mmHg greater in the ID group (absolute rises 16.1 and 10.7 mmHg, respectively; 95% CI for difference, 2.7–9.7 mmHg, P = 0.001). Intravenous iron attenuated the PASP rise in both groups; however, the effect was greater in ID participants than in controls (absolute reductions 11.1 and 6.8 mmHg, respectively; 95% CI for difference in change, –8.3 to –0.3 mmHg, P = 0.035). Serum erythropoietin responses to hypoxia also differed between groups. CONCLUSION. Clinical iron deficiency disturbs normal responses to hypoxia, as evidenced by exaggerated hypoxic pulmonary hypertension that is reversed by subsequent iron administration. Disturbed hypoxia sensing and signaling provides a mechanism through which iron deficiency may be detrimental to human health. TRIAL REGISTRATION. ClinicalTrials.gov (NCT01847352). FUNDING. M.C. Frise is the recipient of a British Heart Foundation Clinical Research Training Fellowship (FS/14/48/30828). K.L. Dorrington is supported by the Dunhill Medical Trust (R178/1110). D.J. Roberts was

  19. Alloantigen presenting function of normal human CD34+ hematopoietic cells.

    PubMed

    Rondelli, D; Andrews, R G; Hansen, J A; Ryncarz, R; Faerber, M A; Anasetti, C

    1996-10-01

    The identification of the CD34 molecule, expressed almost exclusively on human hematopoietic stem cells and committed progenitors, and the development of CD34-specific monoclonal antibodies have made procurement of relatively pure populations of CD34+ marrow cells for autologous transplantation feasible. Characterization of the immunogenicity of CD34+ marrow cells may facilitate the design of successful strategies to use these cells for allogeneic transplantation. CD34+ marrow cells from normal volunteers were enriched to greater than 98% purity by immunoaffinity chromatography on column followed by fluorescence-activated cell sorting. Purified CD34+ cells were tested for expression of HLA-DR and other accessory molecules, and function in hematopoietic colony growth and mixed leukocyte culture (MLC) assays. Greater than 95% CD34+ cells were positive for HLA-DR and 74% +/- 10% were highly positive for CD18, the common beta-chain of a leukointegrin family. CD34+/CD18- cells were small, agranular lymphocytes which contained the majority of precursors for colony-forming cells detected in long-term cultures. They produced almost no stimulation of purified T cells from HLA-DR-incompatible individuals in bulk MLC or in limiting dilution assay. In contrast, CD34+/CD18+ cells were large, were enriched for cells forming mixed colonies in short- but not long-term assays, and were capable of stimulating allogeneic T cells. CD86, a natural ligand for the T-cell activation molecule CD28, was coexpressed with CD18 in 6% +/- 3% of CD34+ cells. CD34+/CD86+ cells, but not CD34+/CD86- cells, exhibited strong alloantigen presenting function. Thus, pluripotent hematopoietic activity and alloantigen presenting function are attributes of distinct subsets of CD34+ marrow cells. CD34+/CD18- or CD34+/CD86- cells may be more effective than either the whole CD34+ population or unseparated marrow in engrafting allogeneic recipients and may also facilitate induction of tolerance.

  20. Effects of formaldehyde on normal xenotransplanted human tracheobronchial epithelium.

    PubMed Central

    Ura, H.; Nowak, P.; Litwin, S.; Watts, P.; Bonfil, R. D.; Klein-Szanto, A. J.

    1989-01-01

    Epithelial cells obtained from autopsies of full-term fetuses or infants less than 1 year old were isolated, amplified in primary cultures and inoculated in deepithelialized rat tracheas. These tracheas were then sealed and transplanted subcutaneously into irradiated athymic nude mice. Four weeks after transplantation the tracheal lumen was completely covered by epithelium, most of which was of mucociliary respiratory type. At this stage, tracheal transplants containing tracheobronchial epithelium from 20 different donors were exposed to silastic devices containing 0, 0.5, 1 and 2 mg paraformaldehyde. The tracheal transplants were examined histologically at 2, 4, 8, and 16 weeks after transplantation. Before sacrifice, all animals were injected with a single pulse of tritiated thymidine. Important epithelial alterations could be seen in the formaldehyde treated transplants with a maximum effect visible at 2 weeks after exposure. The highest dose of 2 mg produced, in most cases, numerous areas of epithelial erosion and inflammation whereas this effect was not as evident with the lower doses. All doses produced areas of hyperplastic epithelium alternating with areas of pleomorphic-atrophic epithelium. Although the differences in predominance of different types of epithelium was not clearly dose-dependent, the labeling index (LI) showed dose dependence between 2 and 4 weeks after initiation of exposure. The maximum mean LI was three to four times higher than normal, although in some focal hyperplastic-metaplastic lesions the LI was increased up to 20 times. These studies show that formaldehyde, although toxic at higher doses, is able to elicit at lower doses a proliferative response of the human respiratory epithelium that is not preceded by a massive toxic effect. This response is similar, although less intense than that of the rat respiratory epithelium in which formaldehyde proved to be a carcinogen. Images Figure 2 Figure 5 PMID:2913828

  1. Color Vision Sensitivity in Normally Dichromatic Species and Humans

    DTIC Science & Technology

    2007-11-02

    postre - ceptoral color processing. To test this, we determined color discrimination thresholds in normally occurring dichromats, including the chipmunk, the 13-lined ground squirrel, and the tree shrew.

  2. Gamma knife radiosurgery to the trigeminal ganglion for treatment of trigeminal neuralgia secondary to vertebrobasilar ectasia

    PubMed Central

    Somaza, Salvador; Hurtado, Wendy; Montilla, Eglee; Ghaleb, Jose

    2014-01-01

    Background: We report the result obtained using Gamma knife stereotactic radiosurgery on the trigeminal ganglion (TG) in a patient with trigeminal neuralgia (TN) secondary to vertebrobasilar ectasia (VBE). Case Description: Retrospective review of medical records corresponding to one patient with VBE-related trigeminal pain treated with radiosurgery. Because of the impossibility of visualization of the entry zone or the path of trigeminal nerve through the pontine cistern, we proceeded with stereotactic radiosurgery directed to the TG. The maximum radiation dose was 86 Gy with a 8-mm and a 4-mm collimator. The follow-up period was 24 months. The pain disappeared in 15 days, passing from Barrow Neurological Institute (BNI) grade V to BNI grade IIIa in 4 months and then to grade I. The patient did not experience noticeable subjective facial numbness. Conclusions: This experience showed that Gamma knife radiosurgery was effective in the management of VBE-related trigeminal pain, using the TG as radiosurgical target. PMID:25593782

  3. Increased phase synchronization of spontaneous calcium oscillations in epileptic human versus normal rat astrocyte cultures

    NASA Astrophysics Data System (ADS)

    Balázsi, Gábor; Cornell-Bell, Ann H.; Moss, Frank

    2003-06-01

    Stochastic synchronization analysis is applied to intracellular calcium oscillations in astrocyte cultures prepared from epileptic human temporal lobe. The same methods are applied to astrocyte cultures prepared from normal rat hippocampus. Our results indicate that phase-repulsive coupling in epileptic human astrocyte cultures is stronger, leading to an increased synchronization in epileptic human compared to normal rat astrocyte cultures.

  4. Radiofrequency trigeminal rhizolysis for the treatment of trigeminal neuralgia secondary to brainstem infarction. Report of two cases.

    PubMed

    Foroohar, M; Herman, M; Heller, S; Levy, R M

    1997-01-15

    Although percutaneous radiofrequency trigeminal rhizolysis (RFL) has been used to treat idiopathic trigeminal neuralgia thought secondary to multiple sclerosis, the use of RFL for trigeminal neuralgia caused by brainstem infarction has not been advocated. The authors report two patients with trigeminal neuralgia following pontine infarction in whom aggressive medical management failed, but who were successfully treated with RFL. Pain relief has persisted for the 3- and 6-year duration of follow-up examinations. Descending trigeminal reticular fibers may be affected by brainstem infarction and result in trigeminal neuralgia; thus, treatment by rhizotomy may be effective in decreasing the peripheral afferent input into the spinal trigeminal nucleus thus decreasing the pain. These two cases demonstrate the utility of RFL in the relief of ischemia-induced trigeminal neuralgia and lead the authors to suggest that its use be broadened to include this indication.

  5. Trigeminal star-like platinum complexes induce cancer cell senescence through quadruplex-mediated telomere dysfunction.

    PubMed

    Zheng, Xiao-Hui; Mu, Ge; Zhong, Yi-Fang; Zhang, Tian-Peng; Cao, Qian; Ji, Liang-Nian; Zhao, Yong; Mao, Zong-Wan

    2016-12-01

    Two trigeminal star-like platinum complexes were synthesized to induce the formation of human telomere G-quadruplex (hTel G4) with extremely high selectivity and affinity. The induced hTel G4 activates strong telomeric DNA damage response (TDDR), resulting in telomere dysfunction and cell senescence.

  6. Meningitis and Bacteremia Due to Neisseria cinerea following a Percutaneous Rhizotomy of the Trigeminal Ganglion.

    PubMed

    von Kietzell, M; Richter, H; Bruderer, T; Goldenberger, D; Emonet, S; Strahm, C

    2016-01-01

    Neisseria cinerea is a human commensal. The first known case of meningitis and bacteremia due to Neisseria cinerea following percutaneous glycerol instillation of the trigeminal ganglion is reported. Conventional phenotypic methods and complete 16S RNA gene sequencing accurately identified the pathogen. Difficulties in differentiation from pathogenic neisseriae are discussed.

  7. Meningitis and Bacteremia Due to Neisseria cinerea following a Percutaneous Rhizotomy of the Trigeminal Ganglion

    PubMed Central

    Richter, H.; Bruderer, T.; Goldenberger, D.; Emonet, S.; Strahm, C.

    2015-01-01

    Neisseria cinerea is a human commensal. The first known case of meningitis and bacteremia due to Neisseria cinerea following percutaneous glycerol instillation of the trigeminal ganglion is reported. Conventional phenotypic methods and complete 16S RNA gene sequencing accurately identified the pathogen. Difficulties in differentiation from pathogenic neisseriae are discussed. PMID:26511743

  8. Molecular and Cellular Mechanisms of Trigeminal Chemosensation

    PubMed Central

    Gerhold, Kristin A.; Bautista, Diana M.

    2010-01-01

    Three sensory systems, olfaction, taste, and somatosensation, are dedicated to the detection of chemicals in the environment. Trigeminal somatosensory neurons enable us to detect a wide range of environmental stimuli, including pressure, temperature, and chemical irritants, within the oral and nasal mucosa. Natural plant-derived irritants have served as powerful pharmacological tools for identifying receptors underlying somatosensation. This is illustrated by the use of capsaicin, menthol, and wasabi to identify the heat-sensitive ion channel TRPV1, the cold-sensitive ion channel TRPM8, and the irritant receptor TRPA1, respectively. In addition to TRP channels, members of the two-pore potassium channel family have also been implicated in trigeminal chemosensation. KCNK18 was recently identified as a target for hydroxy-α-sanshool, the tingling and numbing compound produced in Schezuan peppers and other members of the Xanthoxylum genus. The role of these channels in trigeminal thermosensation and pain will be discussed. PMID:19686135

  9. Trigeminal neuralgia treatment dosimetry of the Cyberknife

    SciTech Connect

    Ho, Anthony; Lo, Anthony T.; Dieterich, Sonja; Soltys, Scott G.; Gibbs, Iris C.; Chang, Steve G.; Adler, John R.

    2012-04-01

    There are 2 Cyberknife units at Stanford University. The robot of 1 Cyberknife is positioned on the patient's right, whereas the second is on the patient's left. The present study examines whether there is any difference in dosimetry when we are treating patients with trigeminal neuralgia when the target is on the right side or the left side of the patient. In addition, we also study whether Monte Carlo dose calculation has any effect on the dosimetry. We concluded that the clinical and dosimetric outcomes of CyberKnife treatment for trigeminal neuralgia are independent of the robot position. Monte Carlo calculation algorithm may be useful in deriving the dose necessary for trigeminal neuralgia treatments.

  10. Trigeminal pathways deliver a low molecular weight drug from the nose to the brain and orofacial structures.

    PubMed

    Johnson, Neil J; Hanson, Leah R; Frey, William H

    2010-06-07

    Intranasal delivery has been shown to noninvasively deliver drugs from the nose to the brain in minutes along the olfactory and trigeminal nerve pathways, bypassing the blood-brain barrier. However, no one has investigated whether nasally applied drugs target orofacial structures, despite high concentrations observed in the trigeminal nerve innervating these tissues. Following intranasal administration of lidocaine to rats, trigeminally innervated structures (teeth, temporomandibular joint (TMJ), and masseter muscle) were found to have up to 20-fold higher tissue concentrations of lidocaine than the brain and blood as measured by ELISA. This concentration difference could allow intranasally administered therapeutics to treat disorders of orofacial structures (i.e., teeth, TMJ, and masseter muscle) without causing unwanted side effects in the brain and the rest of the body. In this study, an intranasally administered infrared dye reached the brain within 10 minutes. Distribution of dye is consistent with dye entering the trigeminal nerve after intranasal administration through three regions with high drug concentrations in the nasal cavity: the middle concha, the maxillary sinus, and the choana. In humans the trigeminal nerve passes through the maxillary sinus to innervate the maxillary teeth. Delivering lidocaine intranasally may provide an effective anesthetic technique for a noninvasive maxillary nerve block. Intranasal delivery could be used to target vaccinations and treat disorders with fewer side effects such as tooth pain, TMJ disorder, trigeminal neuralgia, headache, and brain diseases.

  11. In vitro suppression of normal human bone marrow progenitor cells by human immunodeficiency virus.

    PubMed Central

    Steinberg, H N; Crumpacker, C S; Chatis, P A

    1991-01-01

    Incubation of normal human nonadherent and T-cell-depleted bone marrow cells with HIVIIIB at multiplicities of infection (MOI) ranging from 0.0001:1 to 1:1 reverse transcriptase (RT) units resulted in the dose-dependent suppression of the in vitro growth of erythroid burst-forming unit (BFU-E), granulocyte-macrophage (CFU-GM), and T-lymphocyte (CFU-TL) colonies of progenitor cells. Maximum inhibition of colony formation was observed at a 1:1 ratio of virus to bone marrow cells. At this MOI, BFU-E and CFU-GM colonies were inhibited by 60 to 80%, while CFU-TL colonies were totally suppressed. Inhibition of colony formation was also observed at an MOI of 0.1:1 but not with further log dilutions of the virus. Incubation of the virus with antibody to gp160 resulted in the complete reversal of stem cell suppression and the normalization of colony growth in vitro. For BFU-E and CFU-GM colonies, this reversal was observed with dilutions of antibody up to 1:100 and was no longer observed at titers greater than 1:500. The CFU-TL colony number normalized at titers between 1:10 and 1:50. Human immunodeficiency virus (HIV) also suppressed by 50% the growth of colonies derived from CD34+ stem cell fractions. Infection of CD34+ cells and T-cell-depleted, nonadherent cell fractions was demonstrated by detection with HIV-specific DNA probe following amplification by polymerase chain reaction. The results suggest that HIV can directly infect human bone marrow progenitor cells and affect their ability to proliferate and give rise to colonies in vitro. The results indicate a direct role for the virus in bone marrow suppression and a possible mechanism for the cytopenias observed in patients with AIDS. Images PMID:2002542

  12. Invasive 3-Dimensional Organotypic Neoplasia from Multiple Normal Human Epithelia

    PubMed Central

    Ridky, Todd W.; Chow, Jennifer M.; Wong, David J.; Khavari, Paul A.

    2013-01-01

    Refined cancer models are required to assess the burgeoning number of potential targets for cancer therapeutics within a rapid and clinically relevant context. Here we utilize tumor-associated genetic pathways to transform primary human epithelial cells from epidermis, oropharynx, esophagus, and cervix into genetically defined tumors within a human 3-dimensional (3-D) tissue environment incorporating cell-populated stroma and intact basement membrane. These engineered organotypic tissues recapitulated natural features of tumor progression, including epithelial invasion through basement membrane, a complex process critically required for biologic malignancy in 90% of human cancers. Invasion was rapid, and potentiated by stromal cells. Oncogenic signals in 3-D tissue, but not 2-D culture, resembled gene expression profiles from spontaneous human cancers. Screening well-characterized signaling pathway inhibitors in 3-D organotypic neoplasia helped distil a clinically faithful cancer gene signature. Multi-tissue 3-D human tissue cancer models may provide an efficient and relevant complement to current approaches to characterize cancer progression. PMID:21102459

  13. [Malignant lymphoma in a perineural spreading along trigeminal nerve, which developed as trigeminal neuralgia].

    PubMed

    Mano, Tomoo; Matsuo, Koji; Kobayashi, Yosuke; Kobayashi, Yasushi; Ozawa, Hiroaki; Arakawa, Toshinao

    2014-01-01

    A rare cause of trigeminal neuralgia is malignant lymphoma which spread along the trigeminal nerve. We report a 79-year-old male presented with 4-month history of neuralgic pain in right cheek. He was diagnosed as classical trigeminal neuralgia. It had improved through medication of carbamazepine. Four months later, the dull pain unlike neuralgia complicated on the right cheeks, it was ineffective with the medication. Furthermore, diplopia and facial palsy as the other cranial nerve symptoms appeared. Gadolinium-enhanced magnetic resonance imaging (MRI) revealed contrast-enhanced mass lesion extend both external pterygoid muscle and brainstem through the swelling trigeminal nerve. The patient was pathological diagnosed of diffuse large B cell lymphoma by biopsy. Malignant lymphoma should be considered in the different diagnosis of cases with a minimal single cranial nerve symptom.

  14. Normal human synovial fluid: osmolality and exercise-induced changes.

    PubMed

    Baumgarten, M; Bloebaum, R D; Ross, S D; Campbell, P; Sarmiento, A

    1985-12-01

    We measured the osmolality of human synovial fluid in the knees of healthy young adults following minimum activity and exercise. These results were compared with each subject's blood-serum osmolality. The synovial fluid was hyperosmolal with minimum activity, decreasing to blood-serum levels after exercise.

  15. Vulnerability of Normal Human Mammary Epithelial Cells to Oncogenic Transformation

    DTIC Science & Technology

    2012-04-01

    diverse transformed HMEC lines with defined genetic alterations may aid the identification of potential therapeutic treatments , including...human model systems to test potential therapeutics, could facilitate individualized treatment and possibly prevention. The main variables thought to...epithelial cells. Middle, corresponding cell culture models used in this study. Red, treatment or genetic manipulation used. Cell models are described in

  16. Structural Magnetic Resonance Imaging Can Identify Trigeminal System Abnormalities in Classical Trigeminal Neuralgia

    PubMed Central

    DeSouza, Danielle D.; Hodaie, Mojgan; Davis, Karen D.

    2016-01-01

    Classical trigeminal neuralgia (TN) is a chronic pain disorder that has been described as one of the most severe pains one can suffer. The most prevalent theory of TN etiology is that the trigeminal nerve is compressed at the root entry zone (REZ) by blood vessels. However, there is significant evidence showing a lack of neurovascular compression (NVC) for many cases of classical TN. Furthermore, a considerable number of patients who are asymptomatic have MR evidence of NVC. Since there is no validated animal model that reproduces the clinical features of TN, our understanding of TN pathology mainly comes from biopsy studies that have limitations. Sophisticated structural MRI techniques including diffusion tensor imaging provide new opportunities to assess the trigeminal nerves and CNS to provide insight into TN etiology and pathogenesis. Specifically, studies have used high-resolution structural MRI methods to visualize patterns of trigeminal nerve-vessel relationships and to detect subtle pathological features at the trigeminal REZ. Structural MRI has also identified CNS abnormalities in cortical and subcortical gray matter and white matter and demonstrated that effective neurosurgical treatment for TN is associated with a reversal of specific nerve and brain abnormalities. In conclusion, this review highlights the advanced structural neuroimaging methods that are valuable tools to assess the trigeminal system in TN and may inform our current understanding of TN pathology. These methods may in the future have clinical utility for the development of neuroimaging-based biomarkers of TN. PMID:27807409

  17. Human papilloma virus DNAs immortalize normal human mammary epithelial cells and reduce their growth factor requirements

    SciTech Connect

    Band, V.; Zajchowski, D.; Kulesa, V.; Sager, R. )

    1990-01-01

    Human papilloma virus (HPV) types 16 and 18 are most commonly associated with cervical carcinoma in patients and induce immortalization of human keratinocytes in culture. HPV has not been associated with breast cancer. This report describes the immortalization of normal human mammary epithelial cells (76N) by plasmid pHPV18 or pHPV16, each containing the linearized viral genome. Transfectants were grown continuously for more than 60 passages, whereas 76N cells senesce after 18-20 passages. The transfectants also differ from 76N cells in cloning in a completely defined medium called D2 and growing a minimally supplemented defined medium (D3) containing epidermal growth factor. All transfectant tested contain integrated HPV DNA, express HPV RNA, and produce HPV E7 protein. HPV transfectants do not form tumors in a nude mouse assay. It is concluded that products of the HPV genome induce immortalization of human breast epithelial cells and reduce their growth factor requirements. This result raises the possibility that HPV might be involved in breast cancer. Furthermore, other tissue-specific primary epithelial cells that are presently difficult to grown and investigate may also be immortalized by HPV.

  18. Amino acid immunoreactivity in normal human retina and after brachytherapy.

    PubMed

    de Souza, Clairton F; Acosta, Monica L; Polkinghorne, Philip J; McGhee, Charles N J; Kalloniatis, Michael

    2013-09-01

    We localised amino acids in the mid-peripheral aged human retina and a retina that had undergone radiation treatment 10 years earlier. The distribution pattern of glutamate, γ-amino butyric acid (GABA), glycine, glutamine and taurine, reflected patterns established in the primate retina. The retina that had undergone radiation exposure displayed both anatomical and neurochemical remodelling. The proximal retina comprised around 40 to 45 per cent of the total retina and neuronal kinesis and aberrant neuronal projections were also present. Amino acid neurochemistry was strikingly different with Müller cells displaying GABA loading, glycinergic neurons displaced and displaying a very high level of glycine labelling. We conclude that radiation exposure triggered these changes in the human retina and likely reflects general remodelling of structure and function following ischaemic damage to endothelial cells.

  19. Neurophysiological model of the normal and abnormal human pupil

    NASA Technical Reports Server (NTRS)

    Krenz, W.; Robin, M.; Barez, S.; Stark, L.

    1985-01-01

    Anatomical, experimental, and computer simulation studies were used to determine the structure of the neurophysiological model of the pupil size control system. The computer simulation of this model demonstrates the role played by each of the elements in the neurological pathways influencing the size of the pupil. Simulations of the effect of drugs and common abnormalities in the system help to illustrate the workings of the pathways and processes involved. The simulation program allows the user to select pupil condition (normal or an abnormality), specific site along the neurological pathway (retina, hypothalamus, etc.) drug class input (barbiturate, narcotic, etc.), stimulus/response mode, display mode, stimulus type and input waveform, stimulus or background intensity and frequency, the input and output conditions, and the response at the neuroanatomical site. The model can be used as a teaching aid or as a tool for testing hypotheses regarding the system.

  20. Mineral Density Volume Gradients in Normal and Diseased Human Tissues

    PubMed Central

    Djomehri, Sabra I.; Candell, Susan; Case, Thomas; Browning, Alyssa; Marshall, Grayson W.; Yun, Wenbing; Lau, S. H.; Webb, Samuel; Ho, Sunita P.

    2015-01-01

    Clinical computed tomography provides a single mineral density (MD) value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca) to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT) benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF) using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males) contained significant mineral density variations (enamel: 2820-3095mg/cc, bone: 570-1415mg/cc, cementum: 1240-1340mg/cc, dentin: 1480-1590mg/cc, cementum affected by periodontitis: 1100-1220mg/cc, hypomineralized carious dentin: 345-1450mg/cc, hypermineralized carious dentin: 1815-2740mg/cc, and dental calculus: 1290-1770mg/cc). A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49), hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765) and in cementum (595-990), highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations. PMID:25856386

  1. Mineral density volume gradients in normal and diseased human tissues

    DOE PAGES

    Djomehri, Sabra I.; Candell, Susan; Case, Thomas; ...

    2015-04-09

    Clinical computed tomography provides a single mineral density (MD) value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca) to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT) benchtop unit were correlated with elemental mapping obtained from a microprobe X-raymore » fluorescence (XRF) using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males) contained significant mineral density variations (enamel: 2820-3095mg/cc, bone: 570-1415mg/cc, cementum: 1240-1340mg/cc, dentin: 1480-1590mg/cc, cementum affected by periodontitis: 1100-1220mg/cc, hypomineralized carious dentin: 345-1450mg/cc, hypermineralized carious dentin: 1815-2740mg/cc, and dental calculus: 1290-1770mg/cc). A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49), hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765) and in cementum (595-990), highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations.« less

  2. Mineral density volume gradients in normal and diseased human tissues

    SciTech Connect

    Djomehri, Sabra I.; Candell, Susan; Case, Thomas; Browning, Alyssa; Marshall, Grayson W.; Yun, Wenbing; Lau, S. H.; Webb, Samuel; Ho, Sunita P.; Aikawa, Elena

    2015-04-09

    Clinical computed tomography provides a single mineral density (MD) value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca) to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT) benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF) using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males) contained significant mineral density variations (enamel: 2820-3095mg/cc, bone: 570-1415mg/cc, cementum: 1240-1340mg/cc, dentin: 1480-1590mg/cc, cementum affected by periodontitis: 1100-1220mg/cc, hypomineralized carious dentin: 345-1450mg/cc, hypermineralized carious dentin: 1815-2740mg/cc, and dental calculus: 1290-1770mg/cc). A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49), hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765) and in cementum (595-990), highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations.

  3. Trigeminal Neuralgia due to Vertebrobasilar Dolichoectasia

    PubMed Central

    Campos, Wuilker Knoner; Guasti, André Accioly; da Silva, Benjamin Franklin; Guasti, José Antonio

    2012-01-01

    We presented a case of drug-resistant trigeminal neuralgia attributed to vertebrobasilar dolichoectasia, a rare condition characterized by enlargement, tortuosity, or elongation of intracranial arteries. Dolichoectatic vessels can cause dysfunction of cranial nerves through direct vascular compression. The relationships of vertebrobasilar dolichoectasia with the particularities of neurovascular conflict and images findings are discussed. PMID:22937350

  4. Trigeminal nerve: Anatomic correlation with MR imaging

    SciTech Connect

    Daniels, D.L.; Pech, P.; Pojunas, K.W.; Kilgore, D.P.; Williams, A.L.; Haughton, V.M.

    1986-06-01

    Through correlation with cryomicrotic sections, the appearance of the trigeminal nerve and its branches on magnetic resonance images is described in healthy individuals and in patients with tumors involving this nerve. Coronal images are best for defining the different parts of the nerve and for making a side-to-side comparison. Sagittal images are useful to demonstrate tumors involving the Gasserian ganglion.

  5. Microstructural abnormalities of the trigeminal nerve by diffusion-tensor imaging in trigeminal neuralgia without neurovascular compression

    PubMed Central

    Sunil, Kumar; Ashish, Awasthi; Jayantee, Kalita; Usha Kant, Misra

    2015-01-01

    Microstructural changes of the trigeminal nerve in trigeminal neuralgia due to neurovascular compression have been reported by using diffusion tensor imaging. Other aetiologies such as primary demyelinating lesions, brain stem infarction and nerve root infiltration by tumour affecting the trigeminal pathway may also present as trigeminal neuralgia. The aim of this study was to evaluate the microstructural tissue abnormalities in the trigeminal nerve in symptomatic trigeminal neuralgia not related to neurovascular compression using diffusion tensor imaging. Mean values of the quantitative diffusion parameters of trigeminal nerve, fractional anisotropy and apparent diffusion coefficient, were measured in a group of four symptomatic trigeminal neuralgia patients without neurovascular compression who showed focal non-enhancing T2-hyperintense lesions in the pontine trigeminal pathway. These diffusion parameters were compared between the affected and unaffected sides in the same patient and with four age-matched healthy controls. Cranial magnetic resonance imaging revealed hyperintense lesions in the dorsolateral part of the pons along the central trigeminal pathway on T2-fluid-attenuated inversion recovery sequences. The mean fractional anisotropy value on the affected side was significantly decreased (P = 0.001) compared to the unaffected side and healthy controls. Similarly, the mean apparent diffusion coefficient value was significantly higher (P = 0.001) on the affected side compared to the unaffected side and healthy controls. The cause of trigeminal neuralgia in our patients was abnormal pontine lesions affecting the central trigeminal pathway. The diffusion tensor imaging results suggest that microstructural tissue abnormalities of the trigeminal nerve also exist even in non-neurovascular compression-related trigeminal neuralgia. PMID:26678753

  6. Glucose homeostasis during spontaneous labor in normal human pregnancy.

    PubMed

    Maheux, P C; Bonin, B; Dizazo, A; Guimond, P; Monier, D; Bourque, J; Chiasson, J L

    1996-01-01

    Using stable isotope, glucose turnover was measured in six normal pregnant women during the various stages of labor; during the latent (A1) and active (A2) phases of cervical dilatation, during fetal expulsion (B), and during placental expulsion (C). These data were compared to measurements made in five postpartum women. Pancreatic hormones and cortisol were also measured. In four other normal women undergoing spontaneous labor, catecholamines and free fatty acids were measured. Plasma glucose increased throughout labor from 4.0 +/- 0.2 (A1) to 5.5 +/- 0.5 mmol/L (C) (P < 0.01), compared to 4.7 +/- 0.1 in the postpartum women. Glucose utilization and production were increased throughout labor at 33.4 +/- 3.1 and 32.8 +/- 3.1 mumol/kg min, respectively, compared to 8.2 +/- 0.9 in postpartum women. Glucose metabolic clearance was also increased to 7.5 +/- 0.8 mL/kg.min compared to that in nonpregnant women (1.8 +/- 0.3). Plasma insulin remained at 59 +/- 5 pmol/L during stages A1, A2, and B, but increased to 115 +/- 15 pmol/L during stage C. Plasma glucagon was increased throughout labor at 127 +/- 7 pg/mL, compared to 90 +/- 4 pg/mL in control postpartum women. Plasma cortisol increased during labor from 921 +/- 136 to 2018 +/- 160 nmol/L, compared to 645 +/- 355 during the postpartum period. Epinephrine and norepinephrine also increased during labor from 218 +/- 132 pmol/L and 1.09 +/- 0.16 nmol/L to 1119 +/- 158 and 3.61 +/- 1.04, respectively. It is concluded that labor is associated with a marked increase in glucose utilization and production. These findings suggest that muscle contraction (uterus and skeletal) independent of insulin is a major regulator of glucose utilization during labor. Furthermore, the increase in hepatic glucose production could be favored by an increase in glucagon, catecholamines, and cortisol.

  7. Maintenance of the normal flora of human skin grafts transplanted to mice.

    PubMed

    Kearney, J N; Gowland, G; Holland, K T; Cunliffe, W J

    1982-10-01

    Full-thickness human cadaver skin was maintained on the dorso-lateral thoracic region of hairless mice whose immune rejection mechanism was suppressed using anti-mouse-thymocyte globulin. The bacterial profile of the pregrafted skin did not differ significantly from the normal human microflora. In contrast, the murine skin exhibited quantitative and qualitative differences from the human flora, in particular by the complete absence of Propionibacterium acnes, the dominant bacterium on sebum-rich areas of human skin. The normal microbial profile of the human grafts was maintained throughout the experimental period despite the novel environmental milieu. There was little contamination of the grafts from the normal murine flora. It was concluded that the grafted human skin would provide a realistic model for studying the ecology of human cutaneous micro-organisms.

  8. Reduction of pentylenetetrazole-induced seizure activity in awake rats by seizure-triggered trigeminal nerve stimulation.

    PubMed

    Fanselow, E E; Reid, A P; Nicolelis, M A

    2000-11-01

    Stimulation of the vagus nerve has become an effective method for desynchronizing the highly coherent neural activity typically associated with epileptic seizures. This technique has been used in several animal models of seizures as well as in humans suffering from epilepsy. However, application of this technique has been limited to unilateral stimulation of the vagus nerve, typically delivered according to a fixed duty cycle, independently of whether ongoing seizure activity is present. Here, we report that stimulation of another cranial nerve, the trigeminal nerve, can also cause cortical and thalamic desynchronization, resulting in a reduction of seizure activity in awake rats. Furthermore, we demonstrate that providing this stimulation only when seizure activity begins results in more effective and safer seizure reduction per second of stimulation than with previous methods. Seizure activity induced by intraperitoneal injection of pentylenetetrazole was recorded from microwire electrodes in the thalamus and cortex of awake rats while the infraorbital branch of the trigeminal nerve was stimulated via a chronically implanted nerve cuff electrode. Continuous unilateral stimulation of the trigeminal nerve reduced electrographic seizure activity by up to 78%, and bilateral trigeminal stimulation was even more effective. Using a device that automatically detects seizure activity in real time on the basis of multichannel field potential signals, we demonstrated that seizure-triggered stimulation was more effective than the stimulation protocol involving a fixed duty cycle, in terms of the percent seizure reduction per second of stimulation. In contrast to vagus nerve stimulation studies, no substantial cardiovascular side effects were observed by unilateral or bilateral stimulation of the trigeminal nerve. These findings suggest that trigeminal nerve stimulation is safe in awake rats and should be evaluated as a therapy for human seizures. Furthermore, the results

  9. Effects of Load on Normal Human Osteoblast Function

    NASA Astrophysics Data System (ADS)

    Reseland, J. E.; Devakottai, Sundar; Sundaresan, A.

    2013-02-01

    The effects of load on the secretion and expression of bone markers were tested at different stages of differentiation of primary human osteoblasts. NHOs were both seeded with and without cytodex 3 beads (Sigma),transferred to a NASA rotating wall vessel (modeled microgravity) and harvested at day 7 and day 14. Differentiated and undifferentiated NHOs were loaded at 6-50G for 30 min and compared to cells incubated at 1G after 1 day and 3 days. Collectively the results demonstrate that load has a differential effect on osteoblast differentiation as seen in modeled microgravity and shows specificity in expression of bone cell markers vs. expression of secreted paracrine signaling markers.

  10. Three-Dimensional Normal Human Neural Progenitor Tissue-Like Assemblies: A Model for Persistent Varicell-Zoster Virus Infection and Platform to Study Viral Infectivity and Oxidative Stress and Damage

    NASA Technical Reports Server (NTRS)

    Goodwin, T. J.; McCarthy, M.; Osterrieder, N.; Cohrs, R. J.; Kaufer, B. B.

    2014-01-01

    The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpesvirus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex threedimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6].

  11. Intranasal trigeminal sensitivity: measurements before and after nasal surgery.

    PubMed

    Scheibe, M; Schulze, S; Mueller, C A; Schuster, B; Hummel, Thomas

    2014-01-01

    Nasal surgeries constitute an extensive manipulation of the nasal mucosa and therefore of structures related to trigeminal and olfactory sensitivity. While olfactory changes due to nasal surgery are relatively well investigated, there are only very few studies regarding trigeminal sensitivity. Aim of the present study was to investigate sensory changes after nasal surgery with special regard to the trigeminal sensitivity. In 38 patients prior to and around 12 weeks after nasal surgery the following psychophysical measures were performed: odor identification, odor discrimination, phenyl ethyl alcohol odor threshold, sensitivity to trigeminal stimuli, trigeminal detection thresholds and trigeminal pain thresholds. These results were compared to those of a control group (43 healthy volunteers). Psychophysical olfactory and trigeminal testing showed no major changes in patients after surgery compared to the control group. Independent from the time of measurement higher trigeminal detection thresholds were found in patients compared to healthy subjects, meaning that trigeminal thresholds were already increased before surgery. The present study revealed a decreased trigeminal sensitivity in patients already before surgery. It may be hypothesized that patients also exhibit a decreased sensitivity for nasal airflow, which may also contribute to the patients' impression of impaired nasal breathing.

  12. The physiology of the normal human breast: an exploratory study.

    PubMed

    Mills, Dixie; Gordon, Eva J; Casano, Ashley; Lahti, Sarah Michelle; Nguyen, Tinh; Preston, Alex; Tondre, Julie; Wu, Kuan; Yanase, Tiffany; Chan, Henry; Chia, David; Esfandiari, Mahtash; Himmel, Tiffany; Love, Susan M

    2011-12-01

    The physiology of the nonlactating human breast likely plays a key role in factors that contribute to the etiology of breast cancer and other breast conditions. Although there has been extensive research into the physiology of lactation, few reports explore the physiology of the resting mammary gland, including mechanisms by which compounds such as hormones, drugs, and potential carcinogens enter the breast ducts. The purpose of this study was to explore transport of exogenous drugs into ductal fluid in nonlactating women and determine if their concentrations in the fluid are similar to those observed in the breast milk of lactating women. We selected two compounds that have been well characterized during lactation, caffeine and cimetidine. Caffeine passively diffuses into breast milk, but cimetidine is actively transported and concentrated in breast milk. After ingestion of caffeine and cimetidine, 14 nonlactating subjects had blood drawn and underwent ductal lavage at five time points over 12 h to measure drug levels in the fluid and blood. The concentrations of both caffeine and cimetidine in lavage fluid were substantially less than those observed in breast milk. Our results support recent evidence that the cimetidine transporter is not expressed in the nonlactating mammary gland, and highlight intriguing differences in the physiology and molecular transport of the lactating and nonlactating breast. The findings of this exploratory study warrant further exploration into the physiology of the nonlactating mammary gland to elucidate factors involved in disease initiation and progression.

  13. Analysis of in vivo somatic mutations in normal human cells

    SciTech Connect

    Gupta, P.K.; Sahota, A.; Boyadjiev, S.A.

    1994-09-01

    We have used the APRT locus located at 16q24.3 to study the nature of loss of heterozygosity (LOH) in human T lymphocytes in vivo. T lymphocytes were isolated from blood from APRT (+/{minus}) obligated heterozygotes with known germline mutations. The cells were immediatley placed in culture medium containing 100 {mu}M 2,6-diaminopurine (DAP) to select for drug-resistant clones ({minus}/{minus}) already present. These clones were first examined using polymorphic CA microsatellite repeat markers D16S303 and D16S305 that are distal and proximal to APRT, respectively. The retention of heterozygosity of these markers is suggestive of minor changes in the APRT gene, the exact nature of which were determined by DNA sequencing. Nineteen out of 70 DAP-resistant clones from one heterozygote showed APRT sequence changes. The loss of heterozygosity of markers D16S303 and D16S305 in the remaining clones suggests LOH involving multilocus chromosomal events. These clones were then sequentially typed using additional CA repeat markers proximal and distal to APRT. The extent of LOH in these clones was found to vary from <5 cM to almost the entire 16q arm. Preliminary results suggest that there are multiple sites along the chromosome from which LOH proceeds distally in these clones. Cytogenetic analysis of 10 clones suggested mitotic recombination in 9 and deletion in one. Studies are in progress to further characterize the molecular mechanisms of LOH.

  14. Effect of Ceftaroline on Normal Human Intestinal Microflora▿

    PubMed Central

    Panagiotidis, Georgios; Bäckström, Tobias; Asker-Hagelberg, Charlotte; Jandourek, Alena; Weintraub, Andrej; Nord, Carl Erik

    2010-01-01

    Ceftaroline is a new broad-spectrum cephalosporin being developed for the treatment of serious bacterial infections, including those caused by aerobic Gram-positive and Gram-negative bacteria. The purpose of the present study was to investigate the effect of administration of ceftaroline on the intestinal flora of healthy subjects. Twelve healthy subjects (6 males and 6 females), 20 to 41 years of age, received ceftaroline (600 mg) by intravenous infusion every 12 h (q12h) for 7 days. Plasma and feces were collected for determination of ceftaroline concentration and analysis of fecal flora. Fecal specimens were cultured on nonselective and selective media. Different colony types were counted, isolated in pure culture, and identified to the genus level. All new strains of colonizing bacteria were tested for susceptibility to ceftaroline. The concentrations of ceftaroline in plasma were as follows: on day 2, 17.5 to 34.8 mg/liter; on day 5, 19.7 to 33.2 mg/liter; and on day 7, 18.0 to 29.8 mg/liter. No ceftaroline concentrations were found on day −1, 9, 14, or 21. No measurable concentrations in feces were found on day −1, 2, 5, 7, 9, 14, or 21. There was a minor impact on the numbers of Escherichia coli strains, while the numbers of enterococci and Candida albicans strains were not affected. There were moderate decreases in the numbers of bifidobacteria and lactobacilli during the first 7 days, while the numbers of clostridia increased during the same period. No impact on the numbers of Bacteroides bacteria was noticed. No new colonizing aerobic or anaerobic bacteria resistant to ceftaroline (MIC ≥ 4 mg/liter) were found. Ceftaroline had no significant ecological impact on the human intestinal microflora. PMID:20231399

  15. Mastication induces long-term increases in blood perfusion of the trigeminal principal nucleus.

    PubMed

    Viggiano, A; Manara, R; Conforti, R; Paccone, A; Secondulfo, C; Lorusso, L; Sbordone, L; Di Salle, F; Monda, M; Tedeschi, G; Esposito, F

    2015-12-17

    Understanding mechanisms for vessel tone regulation within the trigeminal nuclei is of great interest because some headache syndromes are due to dysregulation of such mechanisms. Previous experiments on animal models suggest that mastication may alter neuron metabolism and blood supply in these nuclei. To investigate this hypothesis in humans, arterial spin-labeling magnetic resonance imaging (MRI) was used to measure blood perfusion within the principal trigeminal nucleus (Vp) and in the dorsolateral-midbrain (DM, including the mesencephalic trigeminal nucleus) in healthy volunteers, before and immediately after a mastication exercise consisting of chewing a gum on one side of the mouth for 1 h at 1 bite/s. The side preference for masticating was evaluated with a chewing test and the volume of the masseter muscle was measured on T1-weighted MRI scans. The results demonstrated that the mastication exercise caused a perfusion increase within the Vp, but not in the DM. This change was correlated to the preference score for the side where the exercise took place. Moreover, the basal Vp perfusion was correlated to the masseter volume. These results indicate that the local vascular tone of the trigeminal nuclei can be constitutively altered by the chewing practice and by strong or sustained chewing.

  16. Wnt inhibitory factor (WIF)-1 promotes melanogenesis in normal human melanocytes.

    PubMed

    Park, Tae Jun; Kim, Misun; Kim, Hyeran; Park, Sun Yi; Park, Kyoung-Chan; Ortonne, Jean-Paul; Kang, Hee Young

    2014-01-01

    Wnt signaling plays a role in the differentiation as well as the development of melanocytes. Using a microarray analysis, hyperpigmentary skin of melasma expressed high levels of Wnt inhibitory factor-1 (WIF-1) compared with perilesional normal skin. In this study, the expression and functional roles of WIF-1 on melanocytes were investigated. WIF-1 was expressed both in the melanocytes of normal human skin and in cultured melanocytes. The upregulation of WIF-1 on cultured normal human melanocytes significantly induced expressions of MITF and tyrosinase, which were associated with increased melanin content and tyrosinase activity. Consistent with the stimulatory effect of WIF-1, WIF-1 siRNA reduced melanogenesis in the cells. Moreover, WIF-1 increases pigmentation in melanocytes co-cultured with WIF-1-overexpressed fibroblasts and of organ-cultured human skin. These findings suggest that melanocytes express WIF-1 constitutively in vivo and in vitro and that WIF-1 promotes melanogenesis in normal human melanocytes.

  17. Trigeminal trophic syndrome: report of 3 cases affecting the scalp.

    PubMed

    Bolaji, Ranti S; Burrall, Barbara A; Eisen, Daniel B

    2013-12-01

    Trigeminal trophic syndrome (TTS) is a rare condition that results from a prior injury to the sensory distribution of the trigeminal nerve. Patients typically respond to the altered sensation with self-mutilation, most often of the nasal ala. We describe 3 patients with TTS who presented with self-induced ulcerations primarily involving the scalp. Two patients developed delusions of parasitosis (DOP) based on the resulting symptoms of TTS, which is a unique association. Trigeminal trophic syndrome may occur at extranasal sites and in any branch of the trigeminal nerve. The condition should be considered when ulcers are encountered in this nerve distribution. Symptoms such as formication may mimic DOP. Trigeminal trophic syndrome may be differentiated from DOP by the restriction of symptoms and ulcerations to the distribution of the trigeminal nerve.

  18. X Chromosome Abnormalities and Cognitive Development: Implications for Understanding Normal Human Development.

    ERIC Educational Resources Information Center

    Walzer, Stanley

    1985-01-01

    Argues that knowledge from studies of individuals with sex chromosome abnormalities can further understanding of aspects of normal human development. Studies of XO girls, XXY boys, XXX girls, and males with a fragile X chromosome are summarized to demonstrate how results contribute to knowledge about normal cognitive development and about…

  19. Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Breast Carcinogenesis

    PubMed Central

    Margan, Madalin Marius; Jitariu, Andreea Adriana; Nica, Cristian; Raica, Marius

    2016-01-01

    Normal human breast tissue consists of epithelial and nonepithelial cells with different molecular profiles and differentiation grades. This molecular heterogeneity is known to yield abnormal clones that may contribute to the development of breast carcinomas. Stem cells that are found in developing and mature breast tissue are either positive or negative for cytokeratin 19 depending on their subtype. These cells are able to generate carcinogenesis along with mature cells. However, scientific data remains controversial regarding the monoclonal or polyclonal origin of breast carcinomas. The majority of breast carcinomas originate from epithelial cells that normally express BRCA1. The consecutive loss of the BRCA1 gene leads to various abnormalities in epithelial cells. Normal breast epithelial cells also express hypoxia inducible factor (HIF) 1α and HIF-2α that are associated with a high metastatic rate and a poor prognosis for malignant lesions. The nuclear expression of estrogen receptor (ER) and progesterone receptor (PR) in normal human breast tissue is maintained in malignant tissue as well. Several controversies regarding the ability of ER and PR status to predict breast cancer outcome remain. Both ER and PR act as modulators of cell activity in normal human breast tissue. Ki-67 positivity is strongly correlated with tumor grade although its specific role in applied therapy requires further studies. Human epidermal growth factor receptor 2 (HER2) oncoprotein is less expressed in normal human breast specimens but is highly expressed in certain malignant lesions of the breast. Unlike HER2, epidermal growth factor receptor expression is similar in both normal and malignant tissues. Molecular heterogeneity is not only found in breast carcinomas but also in normal breast tissue. Therefore, the molecular mapping of normal human breast tissue might represent a key research area to fully elucidate the mechanisms of breast carcinogenesis. PMID:27382385

  20. From The Cover: Reconstruction of functionally normal and malignant human breast tissues in mice

    NASA Astrophysics Data System (ADS)

    Kuperwasser, Charlotte; Chavarria, Tony; Wu, Min; Magrane, Greg; Gray, Joe W.; Carey, Loucinda; Richardson, Andrea; Weinberg, Robert A.

    2004-04-01

    The study of normal breast epithelial morphogenesis and carcinogenesis in vivo has largely used rodent models. Efforts at studying mammary morphogenesis and cancer with xenotransplanted human epithelial cells have failed to recapitulate the full extent of development seen in the human breast. We have developed an orthotopic xenograft model in which both the stromal and epithelial components of the reconstructed mammary gland are of human origin. Genetic modification of human stromal cells before the implantation of ostensibly normal human mammary epithelial cells resulted in the outgrowth of benign and malignant lesions. This experimental model allows for studies of human epithelial morphogenesis and differentiation in vivo and underscores the critical role of heterotypic interactions in human breast development and carcinogenesis.

  1. Trigeminal autonomic cephalalgias. Part 2: Paroxysmal hemicrania.

    PubMed

    Klasser, Gary D; Balasubramaniam, Ramesh

    2007-11-01

    Paroxysmal hemicrania (PH) is characterized by severe, strictly unilateral pain attacks lasting 2 to 30 minutes localized to orbital, supraorbital, and temporal areas accompanied by ipsilateral autonomic features. It represents 1 of 3 primary headaches classified as trigeminal autonomic cephalalgias. Although PH is rare, patients may present to dental offices seeking relief for their pain. It is important for oral health care providers to recognize PH and render an accurate diagnosis. This will avoid the pitfall of implementing unnecessary and inappropriate traditional dental treatments in hopes of alleviating this neurovascular pain. This is part 2 of a review on trigeminal autonomic cephalalgias and focuses on PH. Aspects of PH including epidemiology, genetics, pathophysiology, clinical presentation, classification and variants, diagnosis, medical management, and dental considerations are discussed.

  2. Late results of bulbar trigeminal tractotomy

    PubMed Central

    Moffie, D.

    1971-01-01

    Re-examination of eight patients in whom bulbar trigeminal tractotomy had been performed 13 to 15 years previously showed that four had no complaints, and the other four had only very slight complaints about pain. In two patients a Spiller-Frazier operation had been performed after tractotomy, in two patients exairesis of the infraorbital or supraorbital nerve had been done. As bulbar trigeminal tractotomy is a major operation and the risk of recurrence is substantial, the indications for this type of operation have to remain very restricted. Theories to explain the recovery of sensation are discussed. It is possible that regeneration of transected fibres is responsible for the loss of analgesia. Images PMID:5571314

  3. Rare cause of trigeminal neuralgia: Meckel's cave meningocele.

    PubMed

    Alobaid, Abdullah; Schaeffer, Todd; Virojanapa, Justin; Dehdashti, Amir R

    2015-07-01

    The most common etiology of classic trigeminal neuralgia is vascular compression. However, other causes must be excluded. It is very unlikely that a meningocele presents with symptomatic trigeminal neuralgia. We present a rare case of a patient presenting with left trigeminal neuralgia. Thin-slice CT and MRI showed a transclival Meckel's cave meningocele. The patient underwent endoscopic repair of the meningocele, which resulted in complete resolution of her symptoms. Meckel's cave meningocele or encephalocele should be considered among the differential diagnoses of trigeminal neuralgia. Meningocele repair should be suggested as the first treatment option in this rare situation.

  4. Can pontine trigeminal T2-hyperintensity suggest herpetic etiology of trigeminal neuralgia?

    PubMed Central

    Russo, Carmela; Ugga, Lorenzo; Mazio, Federica; Capone, Elisa; D’Arco, Felice; Mankad, Kshitij; Caranci, Ferdinando; Marano, Enrico; Brunetti, Arturo

    2016-01-01

    Background Trigeminal neuralgia (TN) is usually classified into two different categories: idiopathic and secondary. We have investigated the frequency of brainstem pontine lesions in patients with idiopathic TN without multiple sclerosis (MS) or stroke, and their association with herpes zoster (HZ) infection. Methods Brain magnetic resonance imaging (MRI) studies of 28 patients with TN were retrospectively reviewed. Results We found seven patients with clinical suspicion of HZ infection and pontine T2 hyperintense lesions, associated with nerve atrophy in one case. Fifteen patients had a neurovascular conflict (NVC) without brainstem involvement, two of them associated with trigeminal atrophy, while four patients had only volumetric reduction of the nerve. In all patients MRI findings were ipsilateral to the side of TN. Conclusions Pontine T2 hyperintensities could be considered as a MRI sign of TN in patients without NVCs. This “trigeminal pontine sign” (TPS) is frequently found in association with herpetic infections. PMID:27942467

  5. Muscle protein analysis. II. Two-dimensional electrophoresis of normal and diseased human skeletal muscle

    SciTech Connect

    Giometti, C.S.; Barany, M.; Danon, M.J.; Anderson, N.G.

    1980-07-01

    High-resolution two-dimensional electrophoresis was used to analyze the major proteins of normal and pathological human-muscle samples. The normal human-muscle pattern contains four myosin light chains: three that co-migrate with the myosin light chains from rabbit fast muscle (extensor digitorum longus), and one that co-migrates with the light chain 2 from rabbit slow muscle (soleus). Of seven Duchenne muscular dystrophy samples, four yielded patterns with decreased amounts of actin and myosin relative to normal muscle, while three samples gave patterns comparable to that for normal muscle. Six samples from patients with myotonic dystrophy also gave normal patterns. In nemaline rod myopathy, in contrast, the pattern was deficient in two of the fast-type myosin light chains.

  6. A Novel Generalized Normal Distribution for Human Longevity and other Negatively Skewed Data

    PubMed Central

    Robertson, Henry T.; Allison, David B.

    2012-01-01

    Negatively skewed data arise occasionally in statistical practice; perhaps the most familiar example is the distribution of human longevity. Although other generalizations of the normal distribution exist, we demonstrate a new alternative that apparently fits human longevity data better. We propose an alternative approach of a normal distribution whose scale parameter is conditioned on attained age. This approach is consistent with previous findings that longevity conditioned on survival to the modal age behaves like a normal distribution. We derive such a distribution and demonstrate its accuracy in modeling human longevity data from life tables. The new distribution is characterized by 1. An intuitively straightforward genesis; 2. Closed forms for the pdf, cdf, mode, quantile, and hazard functions; and 3. Accessibility to non-statisticians, based on its close relationship to the normal distribution. PMID:22623974

  7. Gene expression analysis of primary normal human hepatocytes infected with human hepatitis B virus

    PubMed Central

    Ryu, Hyun Mi; Park, Sung Gyoo; Yea, Sung Su; Jang, Won Hee; Yang, Young-Il; Jung, Guhung

    2006-01-01

    AIM: To find the relationship between hepatitis B virus (HBV) and hepatocytes during the initial state of infection by cDNA microarray. METHODS: Primary normal human hepatocytes (PNHHs) were isolated and infected with HBV. From the PNHHs, RNA was isolated and inverted into complement DNA (cDNA) with Cy3- or Cy5- labeled dUTP for microarray analysis. The labeled cDNA was hybridized with microarray chip, including 4224 cDNAs. From the image of the microarray, expression profiles were produced and some of them were confirmed by RT-PCR, immunoblot analysis, and NF-κB luciferase reporter assay. RESULTS: From the cDNA microarray, we obtained 98 differentially regulated genes. Of the 98 genes, 53 were up regulated and 45 down regulated. Interestingly, in the up regulated genes, we found the TNF signaling pathway-related genes: LT-α, TRAF2, and NIK. By using RT-PCR, we confirmed the up-regulation of these genes in HepG2, Huh7, and Chang liver cells, which were transfected with pHBV1.2×, a plasmid encoding all HBV messages. Moreover, these three genes participated in HBV-mediated NF-κB activation. CONCLUSION: During the initial state of HBV infection, hepatocytes facilitate the activation of NF-κB through up regulation of LT-α, TRAF2, and NIK. PMID:16937494

  8. Long-term culture and functional characterization of follicular cells from adult normal human thyroids.

    PubMed Central

    Curcio, F; Ambesi-Impiombato, F S; Perrella, G; Coon, H G

    1994-01-01

    We have obtained long-term cultures of differentiated proliferating follicular cells from normal adult human thyroid glands. In vitro growth of such human cells has been sustained by a modified F-12 medium, supplemented with bovine hypothalamus and pituitary extracts and no added thyrotropin. Cultures have been expanded, cloned, frozen, successfully retrieved, and characterized. Functional characterization of these cells shows constitutive thyroglobulin production and release and thyrotropin-dependent adenosine 3',5'-cyclic monophosphate production, the latter apparently not associated with significant increases in DNA synthesis or cell proliferation. Genetic characterization of these cells by chromosome counting showed the normal diploid chromosome number. The ability to cultivate differentiated human thyroid follicular cells in long-term culture opens possibilities for investigating the transduction pathways of thyrotropin stimulation in normal and pathological human tissues, developing clinically relevant in vitro assays, and considering cellular and molecular therapies. Images PMID:8090760

  9. Maturation-associated gene expression profiles along normal human bone marrow monopoiesis.

    PubMed

    Mello, Fabiana V; Alves, Liliane R; Land, Marcelo G P; Teodósio, Cristina; Sanchez, María-Luz; Bárcena, Paloma; Peres, Rodrigo T; Pedreira, Carlos E; Costa, Elaine S; Orfao, Alberto

    2017-02-01

    Human monopoiesis is a tightly coordinated process which starts in the bone marrow (BM) haematopoietic stem cell (HSC) compartment and leads to the production of circulating blood mature monocytes. Although mature monocytes/macrophages have been extensively studied in both normal or inflammatory conditions, monopoiesis has only been assessed in vitro and in vivo animal models, due to low frequency of the monocytic precursors in the normal human BM. Here we investigated the transcriptional profile along normal human BM monopoiesis. Five distinct maturation-associated stages of monocytic precursors were identified and isolated from (fresh) normal human BM through fluorescence-activated cell sorting, and the gene expression profile (GEP) of each monocytic precursor subset was analysed by DNA-oligonucleotide microarrays. Overall, >6000 genes (18% of the genes investigated) were expressed in ≥1 stage of BM monopoiesis at stable or variable amounts, showing early decrease in cell proliferation with increased levels of expression of genes linked with cell differentiation. The here-defined GEP of normal human BM monopoiesis might contribute to better understand monocytic differentiation and the identification of novel monocytic candidate markers, while also providing a frame of reference for the study of monocytic maturation in both neoplastic and non-neoplastic disease conditions involving monocytic precursor cells.

  10. Human Normal Bronchial Epithelial Cells: A Novel In Vitro Cell Model for Toxicity Evaluation

    PubMed Central

    Huang, Haiyan; Xia, Bo; Liu, Hongya; Li, Jie; Lin, Shaolin; Li, Tiyuan; Liu, Jianjun; Li, Hui

    2015-01-01

    Human normal cell-based systems are needed for drug discovery and toxicity evaluation. hTERT or viral genes transduced human cells are currently widely used for these studies, while these cells exhibited abnormal differentiation potential or response to biological and chemical signals. In this study, we established human normal bronchial epithelial cells (HNBEC) using a defined primary epithelial cell culture medium without transduction of exogenous genes. This system may involve decreased IL-1 signaling and enhanced Wnt signaling in cells. Our data demonstrated that HNBEC exhibited a normal diploid karyotype. They formed well-defined spheres in matrigel 3D culture while cancer cells (HeLa) formed disorganized aggregates. HNBEC cells possessed a normal cellular response to DNA damage and did not induce tumor formation in vivo by xenograft assays. Importantly, we assessed the potential of these cells in toxicity evaluation of the common occupational toxicants that may affect human respiratory system. Our results demonstrated that HNBEC cells are more sensitive to exposure of 10~20 nm-sized SiO2, Cr(VI) and B(a)P compared to 16HBE cells (a SV40-immortalized human bronchial epithelial cells). This study provides a novel in vitro human cells-based model for toxicity evaluation, may also be facilitating studies in basic cell biology, cancer biology and drug discovery. PMID:25861018

  11. Meckel's cave epidermoid with trigeminal neuralgia: CT findings.

    PubMed

    Kapila, A; Steinbaum, S; Chakeres, D W

    1984-12-01

    An epidermoid tumor of Meckel's cave was found in a middle-aged woman with trigeminal neuralgia. On CT the lesion had negative attenuation numbers of fat and extended from an expanded Meckel's cave through the porous trigeminus into the ambient and cerebellopontine angle cisterns. Surgical excision provided relief of the patient's trigeminal neuralgia.

  12. Effect of resveratrol and zinc on intracellular zinc status in normal human prostate epithelial cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To evaluate the influence of resveratrol on cellular zinc status, normal human prostate epithelial (NHPrE) cells were treated with 6 levels of resveratrol (0, 0.5, 1, 2.5, 5 and 10 microM) and 4 levels of zinc [0, 4, 16, and 32 microM for zinc-deficient (ZD), zinc-normal (ZN), zinc-adequate (ZA), an...

  13. Duchenne Muscular Dystrophy Gene Expression in Normal and Diseased Human Muscle

    NASA Astrophysics Data System (ADS)

    Oronzi Scott, M.; Sylvester, J. E.; Heiman-Patterson, T.; Shi, Y.-J.; Fieles, W.; Stedman, H.; Burghes, A.; Ray, P.; Worton, R.; Fischbeck, K. H.

    1988-03-01

    A probe for the 5' end of the Duchenne muscular dystrophy (DMD) gene was used to study expression of the gene in normal human muscle, myogenic cell cultures, and muscle from patients with DMD. Expression was found in RNA from normal fetal muscle, adult cardiac and skeletal muscle, and cultured muscle after myoblast fusion. In DMD muscle, expression of this portion of the gene was also revealed by in situ RNA hybridization, particularly in regenerating muscle fibers.

  14. Effect of inhaled 15-(s)-hydroxyeicosatetraenoic acid on tracheobronchial clearance in normal human airways.

    PubMed Central

    Lai, C K; Polosa, R; Pavia, D; Hasani, A; Agnew, J E; Clarke, S W; Holgate, S T

    1991-01-01

    15-(s)-Hydroxyeicosatetraenoic acid (15-HETE) is the predominant metabolite of arachidonic acid in normal and asthmatic human airways and a potent mucus secretagogue in canine and human airways. A study was carried out on the effect of inhaled 15-HETE on tracheobronchial clearance, measured for six hours by a radioaerosol technique, in 10 normal subjects. Subjects inhaled 80 nmol 15-HETE or the diluent (sodium phosphate buffer) on two occasions at least two weeks apart in a double blind and randomised fashion (20 minutes after radioaerosol inhalation. Tracheobronchial clearance after inhaled 15-HETE was almost identical to that after placebo for all measurements up to six hours. It is concluded that 15-HETE has no effect on tracheobronchial clearance in normal human airways and is unlikely to account for the impaired mucociliary clearance seen in asthma. PMID:1858085

  15. Structure and function of adenylate kinase isozymes in normal humans and muscular dystrophy patients.

    PubMed

    Hamada, M; Takenaka, H; Fukumoto, K; Fukamachi, S; Yamaguchi, T; Sumida, M; Shiosaka, T; Kurokawa, Y; Okuda, H; Kuby, S A

    1987-01-01

    Two isozymes of adenylate kinase from human Duchenne muscular dystrophy serum, one of which was an aberrant form specific to DMD patients, were separated by Blue Sepharose CL-6B affinity chromatography. The separated aberrant form possessed a molecular weight of 98,000 +/- 1,500, whereas the normal serum isozyme had a weight of 87,000 +/- 1,600, as determined by SDS-polyacrylamide gel electrophoresis, gel filtration, and sedimentation equilibrium. The sedimentation coefficients were 5.8 S and 5.6 S for the aberrant form and the normal form, respectively. Both serum isozymes are tetramers. The subunit size of the aberrant isozyme (Mr = 24,700) was very similar to that of the normal human liver isozyme, and the subunit size of the normal isozyme (Mr = 21,700) was very similar to that of the normal human muscle enzyme. The amino acid composition of the normal serum isozyme was similar to that of the muscle-type enzyme, and that of the aberrant isozyme was similar to that of the liver enzyme, with some exceptions in both cases.

  16. Magnetic measurements on human erythrocytes: Normal, beta thalassemia major, and sickle

    NASA Astrophysics Data System (ADS)

    Sakhnini, Lama

    2003-05-01

    In this article magnetic measurements were made on human erythrocytes at different hemoglobin states (normal and reduced hemoglobin). Different blood samples: normal, beta thalassemia major, and sickle were studied. Beta thalassemia major and sickle samples were taken from patients receiving lifelong blood transfusion treatment. All samples examined exhibited diamagnetic behavior. Beta thalassemia major and sickle samples showed higher diamagnetic susceptibilities than that for the normal, which was attributed to the increase of membrane to hemoglobin volume ratio of the abnormal cells. Magnetic measurements showed that the erythrocytes in the reduced state showed less diamagnetic response in comparison with erythrocytes in the normal state. Analysis of the paramagnetic component of magnetization curves gave an effective magnetic moment of μeff=7.6 μB per reduced hemoglobin molecule. The same procedure was applied to sickle and beta thalassemia major samples and values for μeff were found to be comparable to that of the normal erythrocytes.

  17. Normalization of human RNA-seq experiments using chimpanzee RNA as a spike-in standard.

    PubMed

    Yu, Hannah; Hahn, Yoonsoo; Park, Sang-Ryoul; Chung, Sun-Ku; Jeong, Sangkyun; Yang, Inchul

    2016-08-24

    Normalization of human RNA-seq experiments employing chimpanzee RNA as a spike-in standard is reported. Human and chimpanzee RNAs exhibit single nucleotide variations (SNVs) in average 210-bp intervals. Spike-in chimpanzee RNA would behave the same as the human counterparts during the whole NGS procedures owing to the high sequence similarity. After discrimination of species origins of the NGS reads based on SNVs, the chimpanzee reads were used to read-by-read normalize biases and variations of human reads. By this approach, as many as 10,119 transcripts were simultaneously normalized for the entire NGS procedures leading to accurate and reproducible quantification of differential gene expression. In addition, incomparable data sets from different in-process degradations or from different library preparation methods were made well comparable by the normalization. Based on these results, we expect that the normalization approaches using near neighbor genomes as internal standards could be employed as a standard protocol, which will improve both accuracy and comparability of NGS results across different sample batches, laboratories and NGS platforms.

  18. High field magnetic resonance imaging of normal and pathologic human medulla oblongata.

    PubMed

    Vandersteen, M; Beuls, E; Gelan, J; Adriaensens, P; Vanormelingen, L; Palmers, Y; Freling, G

    1994-02-01

    High field proton magnetic resonance (MR) imaging has been applied to depict the MR appearance of the normal excised human cervicomedullary junction, based on which neuropathologic specimens can be described. More specifically, two normal cases and one case of Chiari deformity were imaged in the transverse, sagittal, and coronal dimensions using a 9.4 Tesla vertical bore magnet. The MR images of the normal specimens reveal most of the neuroanatomical microstructures described in literature. An accurate description of the Chiari deformity could be made by comparing the MR reference images with those of the pathologic specimen. All MR detected abnormalities were confirmed by histopathology, by which no additional lesions could be found.

  19. The effect of methylprednisolone on intracellular calcium of normal and dystrophic human skeletal muscle cells.

    PubMed

    Vandebrouck, C; Imbert, N; Duport, G; Cognard, C; Raymond, G

    1999-07-09

    Clinical trials have shown that a glucocorticoid, the methyiprednisolone (PDN), has a beneficial effect on muscle strength and function in Duchenne muscular dystrophy (DMD) patients. The aim of this study was to test if the effect of PDN could be mediated via a possible action on intracellular calcium. The intracellular calcium activity, at rest and during calcium mobilizing drug superfusion protocols was recorded in normal and dystrophic human cocultured muscle cells. PDN (10 microM) pretreatment induced an elevation of the resting calcium concentration of 51, 34 and 38% in proliferating normal myoblasts, DMD myoblasts and DMD myotubes, respectively, while normal myotubes resting [Ca2+]i was not altered.

  20. Deep sequencing as a probe of normal stem cell fate and preneoplasia in human epidermis

    PubMed Central

    Simons, Benjamin D.

    2016-01-01

    Using deep sequencing technology, methods based on the sporadic acquisition of somatic DNA mutations in human tissues have been used to trace the clonal evolution of progenitor cells in diseased states. However, the potential of these approaches to explore cell fate behavior of normal tissues and the initiation of preneoplasia remain underexploited. Focusing on the results of a recent deep sequencing study of eyelid epidermis, we show that the quantitative analysis of mutant clone size provides a general method to resolve the pattern of normal stem cell fate and to detect and characterize the mutational signature of rare field transformations in human tissues, with implications for the early detection of preneoplasia. PMID:26699486

  1. Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

    SciTech Connect

    Aubuchon, Adam C.; Chan, Michael D.; Lovato, James F.; Balamucki, Christopher J.; Ellis, Thomas L.; Tatter, Stephen B.; McMullen, Kevin P.; Munley, Michael T.; Deguzman, Allan F.; Ekstrand, Kenneth E.; Bourland, J. Daniel; Shaw, Edward G.

    2011-11-15

    Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90). The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

  2. Tumour and normal tissue radiobiology in mouse models: how close are mice to mini-humans?

    PubMed

    Koontz, Bridget F; Verhaegen, Frank; De Ruysscher, Dirk

    2017-01-01

    Animal modelling is essential to the study of radiobiology and the advancement of clinical radiation oncology by providing preclinical data. Mouse models in particular have been highly utilized in the study of both tumour and normal tissue radiobiology because of their cost effectiveness and versatility. Technology has significantly advanced in preclinical radiation techniques to allow highly conformal image-guided irradiation of small animals in an effort to mimic human treatment capabilities. However, the biological and physical limitations of animal modelling should be recognized and considered when interpreting preclinical radiotherapy (RT) studies. Murine tumour and normal tissue radioresponse has been shown to vary from human cellular and molecular pathways. Small animal irradiation techniques utilize different anatomical boundaries and may have different physical properties than human RT. This review addresses the difference between the human condition and mouse models and discusses possible strategies for future refinement of murine models of cancer and radiation for the benefit of both basic radiobiology and clinical translation.

  3. BACE1 and BACE2 in pathologic and normal human muscle.

    PubMed

    Vattemi, Gaetano; Engel, W King; McFerrin, Janis; Pastorino, Lucia; Buxbaum, Joseph D; Askanas, Valerie

    2003-02-01

    BACE1 and BACE2 are recently discovered enzymes participating in processing of amyloid beta precursor protein (AbetaPP). Their discovery is contributing importantly to understanding the mechanism of amyloid-beta generation, and hence the pathogenesis of Alzheimer's disease (AD). Sporadic inclusion-body myositis (s-IBM) and hereditary inclusion-body myopathy (h-IBM) are progressive muscle diseases in which overproduction of AbetaPP and accumulation of its presumably toxic proteolytic product amyloid-beta (Abeta) in abnormal muscle fibers appear to play an important upstream role in the pathogenic cascade. In normal human muscle AbetaPP was also shown to be present and presumably playing a role (a) at neuromuscular junctions and (b) during muscle development. To investigate whether BACE1 and BACE2 play a role in normal and diseased human muscle, we have now studied them by immunocytochemistry and immunoblotting in 35 human muscle biopsies, including: 5 s-IBM; 5 chromosome-9p1-linked quadriceps-sparing h-IBM; and 25 control muscle biopsies. In addition, expression of BACE1 and BACE2 was studied in normal cultured human muscle. Our studies demonstrate that BACE1 and BACE2 (a) are expressed in normal adult muscle at the postsynaptic domain of neuromuscular junctions, and in cultured human muscle; (b) are accumulated in the form of plaque-like inclusions in both s-IBM and h-IBM vacuolated muscle fibers; and (c) are immunoreactive in necrotizing muscle fibers. Accordingly, BACE1 and BACE2 participate in normal and abnormal processes of human muscle, suggesting that their functions are broader than previously thought.

  4. Distinct p53 genomic binding patterns in normal and cancer-derived human cells

    SciTech Connect

    Botcheva K.; McCorkle S. R.; McCombie W. R.; Dunn J. J.; Anderson C. W.

    2011-12-15

    We report here genome-wide analysis of the tumor suppressor p53 binding sites in normal human cells. 743 high-confidence ChIP-seq peaks representing putative genomic binding sites were identified in normal IMR90 fibroblasts using a reference chromatin sample. More than 40% were located within 2 kb of a transcription start site (TSS), a distribution similar to that documented for individually studied, functional p53 binding sites and, to date, not observed by previous p53 genome-wide studies. Nearly half of the high-confidence binding sites in the IMR90 cells reside in CpG islands, in marked contrast to sites reported in cancer-derived cells. The distinct genomic features of the IMR90 binding sites do not reflect a distinct preference for specific sequences, since the de novo developed p53 motif based on our study is similar to those reported by genome-wide studies of cancer cells. More likely, the different chromatin landscape in normal, compared with cancer-derived cells, influences p53 binding via modulating availability of the sites. We compared the IMR90 ChIPseq peaks to the recently published IMR90 methylome1 and demonstrated that they are enriched at hypomethylated DNA. Our study represents the first genome-wide, de novo mapping of p53 binding sites in normal human cells and reveals that p53 binding sites reside in distinct genomic landscapes in normal and cancer-derived human cells.

  5. Modeling normal and malignant human hematopoiesis in vivo through newborn NSG xenotransplantation.

    PubMed

    Ishikawa, Fumihiko

    2013-12-01

    Various strains of immune-compromised mice have been developed to investigate human normal and malignant stem cells in vivo. NOD/SCID mice harboring complete null mutation of Il2rg (NSG mice) lack T cells, B cells, and NK cells, and support high levels of engraftment by human cord blood hematopoietic stem cells (CB HSCs) and acute myeloid leukemia stem cells (AML LSCs). In addition to achieving high levels of human hematopoietic cell engraftment, use of newborn NSG mice as recipients has enabled the investigation into how human CB HSCs generate mature immune subsets in vivo. Moreover, through establishing an in vivo model of human primary AML by xenotransplantation of human LSCs into newborn NSG mice, functional properties of human AML such as cell cycle, location, and self-renewal capacity can be examined in vivo. Newborn NSG xenogeneic transplantation model may facilitate the understanding of human normal and malignant hematopoiesis and contribute to the development of novel therapies against hematologic diseases.

  6. A second trigeminal CGRP receptor: function and expression of the AMY1 receptor

    PubMed Central

    Walker, Christopher S; Eftekhari, Sajedeh; Bower, Rebekah L; Wilderman, Andrea; Insel, Paul A; Edvinsson, Lars; Waldvogel, Henry J; Jamaluddin, Muhammad A; Russo, Andrew F; Hay, Debbie L

    2015-01-01

    Objective The trigeminovascular system plays a central role in migraine, a condition in need of new treatments. The neuropeptide, calcitonin gene-related peptide (CGRP), is proposed as causative in migraine and is the subject of intensive drug discovery efforts. This study explores the expression and functionality of two CGRP receptor candidates in the sensory trigeminal system. Methods Receptor expression was determined using Taqman G protein-coupled receptor arrays and immunohistochemistry in trigeminal ganglia (TG) and the spinal trigeminal complex of the brainstem in rat and human. Receptor pharmacology was quantified using sensitive signaling assays in primary rat TG neurons. Results mRNA and histological expression analysis in rat and human samples revealed the presence of two CGRP-responsive receptors (AMY1: calcitonin receptor/receptor activity-modifying protein 1 [RAMP1]) and the CGRP receptor (calcitonin receptor-like receptor/RAMP1). In support of this finding, quantification of agonist and antagonist potencies revealed a dual population of functional CGRP-responsive receptors in primary rat TG neurons. Interpretation The unexpected presence of a functional non-canonical CGRP receptor (AMY1) at neural sites important for craniofacial pain has important implications for targeting the CGRP axis in migraine. PMID:26125036

  7. Dopamine D2 receptor expression in the corticotroph cells of the human normal pituitary gland.

    PubMed

    Pivonello, Rosario; Waaijers, Marlijn; Kros, Johan M; Pivonello, Claudia; de Angelis, Cristina; Cozzolino, Alessia; Colao, Annamaria; Lamberts, Steven W J; Hofland, Leo J

    2016-10-13

    The dopamine D2 receptor is the main dopamine receptor expressed in the human normal pituitary gland. The aim of the current study was to evaluate dopamine D2 receptor expression in the corticotroph cell populations of the anterior lobe and pars intermedia, as well as posterior lobe of the human normal pituitary gland by immunohistochemistry. Human normal pituitary gland samples obtained from routine autopsies were used for the study. In all cases, histology together with immunostaining for adrenocorticotropic hormone, melanocyte-stimulating hormone, prolactin, and neurofilaments were performed and compared to the immunostaining for D2 receptor. D2 receptor was heterogeneously expressed in the majority of the cell populations of the anterior and posterior lobe as well as in the area localized between the anterior and posterior lobe, and arbitrary defined as "intermediate zone". This zone, characterized by the presence of nerve fibers included the residual pars intermedia represented by the colloid-filled cysts lined by the remnant melanotroph cells strongly expressing D2 receptors, and clusters of corticotroph cells, belonging to the anterior lobe but localized within the cysts and adjacent to the posterior lobe, variably expressing D2 receptors. D2 dopamine receptor is expressed in the majority of the cell populations of the human normal pituitary gland, and particularly, in the different corticotroph cell populations localized in the anterior lobe and the intermediate zone of the pituitary gland.

  8. Assessing the Toxicities of Regulated and Unregulated Disinfection By-products in Normal Human Colon Cells.

    EPA Science Inventory

    The presence of over six hundred disinfection by-products (DBPs) and less than half of the total organic halides present in finished water has created a need for short-term in vitro assays to address toxicities that might be associated with human exposure. . We are using a normal...

  9. Looking at Images with Human Figures: Comparison between Autistic and Normal Children.

    ERIC Educational Resources Information Center

    van der Geest, J. N.; Kemner, C.; Camfferman, G.; Verbaten, M. N.; van Engeland, H.

    2002-01-01

    In this study, the looking behavior of 16 autistic and 14 non-autistic children toward cartoon-like scenes that included a human figure was measured quantitatively using an infrared eye-tracking device. Fixation behavior of autistic children was similar to that of their age-and IQ-matched normal peers. Results do not support the idea that autistic…

  10. Identification of normal and cancerous human colorectal muscularis propria by multiphoton microscopy in different sections

    NASA Astrophysics Data System (ADS)

    Zhou, Yi; Chen, Zhifen; Kang, Deyong; li, Lianhuang; Zhuo, Shuangmu; Zhu, Xiaoqin; Guan, Guoxian; Chen, Jianxin

    2016-01-01

    Multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) as a potential diagnostic tool is attractive. MPM can effectively provide information about morphological and biochemical changes in biological tissues at the molecular level. In this paper, we attempt to identify normal and cancerous human colorectal muscularis propria by multiphoton microscopy in different sections (both in transverse and longitudinal sections). The results show that MPM can display different microstructure changes in the transverse and longitudinal sections of colorectal muscularis propria. MPM also can quantitatively describe the alteration of collagen content between normal and cancerous muscle layers. These are important pathological findings that MPM images can bring more detailed complementary information about tissue architecture and cell morphology through observing the transverse and longitudinal sections of colorectal muscularis propria. This work demonstrates that MPM can be better for identifying the microstructural characteristics of normal and cancerous human colorectal muscularis propria in different sections.

  11. Temporomandibular joint pain: a critical role for Trpv4 in the trigeminal ganglion.

    PubMed

    Chen, Yong; Williams, Susan H; McNulty, Amy L; Hong, Ji Hee; Lee, Suk Hee; Rothfusz, Nicole E; Parekh, Puja K; Moore, Carlene; Gereau, Robert W; Taylor, Andrea B; Wang, Fan; Guilak, Farshid; Liedtke, Wolfgang

    2013-08-01

    Temporomandibular joint disorder (TMJD) is known for its mastication-associated pain. TMJD is medically relevant because of its prevalence, severity, chronicity, the therapy-refractoriness of its pain, and its largely elusive pathogenesis. Against this background, we sought to investigate the pathogenetic contributions of the calcium-permeable TRPV4 ion channel, robustly expressed in the trigeminal ganglion sensory neurons, to TMJ inflammation and pain behavior. We demonstrate here that TRPV4 is critical for TMJ-inflammation-evoked pain behavior in mice and that trigeminal ganglion pronociceptive changes are TRPV4-dependent. As a quantitative metric, bite force was recorded as evidence of masticatory sensitization, in keeping with human translational studies. In Trpv4(-/-) mice with TMJ inflammation, attenuation of bite force was significantly less than in wildtype (WT) mice. Similar effects were seen with systemic application of a specific TRPV4 inhibitor. TMJ inflammation and mandibular bony changes were apparent after injections of complete Freund adjuvant but were remarkably independent of the Trpv4 genotype. It was intriguing that, as a result of TMJ inflammation, WT mice exhibited significant upregulation of TRPV4 and phosphorylated extracellular-signal-regulated kinase (ERK) in TMJ-innervating trigeminal sensory neurons, which were absent in Trpv4(-/-) mice. Mice with genetically-impaired MEK/ERK phosphorylation in neurons showed resistance to reduction of bite force similar to that of Trpv4(-/-) mice. Thus, TRPV4 is necessary for masticatory sensitization in TMJ inflammation and probably functions upstream of MEK/ERK phosphorylation in trigeminal ganglion sensory neurons in vivo. TRPV4 therefore represents a novel pronociceptive target in TMJ inflammation and should be considered a target of interest in human TMJD.

  12. Glucagon-like-peptide-1 receptor expression in normal and diseased human thyroid and pancreas.

    PubMed

    Waser, Beatrice; Blank, Annika; Karamitopoulou, Eva; Perren, Aurel; Reubi, Jean C

    2015-03-01

    Glucagon-like-peptide-1 (GLP1) analogs may induce thyroid or pancreatic diseases in animals, raising questions about their use in diabetic patients. There is, however, controversy regarding expression of GLP1 receptors (GLP1R) in human normal and diseased thyroid and pancreas. Here, 221 human thyroid and pancreas samples were analyzed for GLP1R immunohistochemistry and compared with quantitative in vitro GLP1R autoradiography. Neither normal nor hyperplastic human thyroids containing parafollicular C cells express GLP1R with either method. Papillary thyroid cancer do not, and medullary thyroid carcinomas rarely express GLP1R. Insulin- and somatostatin-producing cells in the normal pancreas express a high density of GLP1R, whereas acinar cells express them in low amounts. Ductal epithelial cells do not express GLP1R. All benign insulinomas express high densities of GLP1R, whereas malignant insulinomas rarely express them. All ductal pancreatic carcinomas are GLP1R negative, whereas 6/20 PanIN 1/2 and 0/12 PanIN 3 express GLP1R. Therefore, normal thyroid, including normal and hyperplastic C cells, or papillary thyroid cancer are not targets for GLP1 analogs in humans. Conversely, all pancreatic insulin- and somatostatin-producing cells are physiological GLP1 targets, as well as most acini. As normal ductal epithelial cells or PanIN 3 or ductal pancreatic carcinomas do not express GLP1R, it seems unlikely that GLP1R is related to neoplastic transformation in pancreas. GLP1R-positive medullary thyroid carcinomas and all benign insulinomas are candidates for in vivo GLP1R targeting.

  13. Genome-wide quantification of rare somatic mutations in normal human tissues using massively parallel sequencing

    PubMed Central

    Hoang, Margaret L.; Kinde, Isaac; Tomasetti, Cristian; McMahon, K. Wyatt; Rosenquist, Thomas A.; Grollman, Arthur P.; Kinzler, Kenneth W.; Vogelstein, Bert; Papadopoulos, Nickolas

    2016-01-01

    We present the bottleneck sequencing system (BotSeqS), a next-generation sequencing method that simultaneously quantifies rare somatic point mutations across the mitochondrial and nuclear genomes. BotSeqS combines molecular barcoding with a simple dilution step immediately before library amplification. We use BotSeqS to show age- and tissue-dependent accumulations of rare mutations and demonstrate that somatic mutational burden in normal human tissues can vary by several orders of magnitude, depending on biologic and environmental factors. We further show major differences between the mutational patterns of the mitochondrial and nuclear genomes in normal tissues. Lastly, the mutation spectra of normal tissues were different from each other, but similar to those of the cancers that arose in them. This technology can provide insights into the number and nature of genetic alterations in normal tissues and can be used to address a variety of fundamental questions about the genomes of diseased tissues. PMID:27528664

  14. Endogenous Inhibition of the Trigeminally Evoked Neurotransmission to Cardiac Vagal Neurons by Muscarinic Acetylcholine Receptors

    PubMed Central

    Gorini, C.; Philbin, K.; Bateman, R.

    2010-01-01

    Stimulation of the nasal mucosa by airborne irritants or water evokes a pronounced bradycardia accompanied by peripheral vasoconstriction and apnea. The dive response, which includes the trigeminocardiac reflex, is among the most powerful autonomic responses. These responses slow the heart rate and reduce myocardial oxygen consumption. Although normally cardioprotective, exaggeration of this reflex can be detrimental and has been implicated in cardiorespiratory diseases, including sudden infant death syndrome (SIDS). An essential component of the diving response and trigeminocardiac reflex is activation of the parasympathetic cardiac vagal neurons (CVNs) in the nucleus ambiguus that control heart rate. This study examined the involvement of cholinergic receptors in trigeminally evoked excitatory postsynaptic currents in CVNs in an in vitro preparation from rats. CVNs were identified using a retrograde tracer injected into the fat pads at the base of the heart. Application of the acetylcholinesterase inhibitor neostigmine significantly decreased the amplitude of glutamatergic neurotransmission to CVNs on stimulation of trigeminal fibers. Whereas nicotine did not have any effect on the glutamatergic responses, the muscarinic acetylcholine receptor (mAChR) agonist bethanechol significantly decreased the excitatory neurotransmission. Atropine, an mAChR antagonist, facilitated these responses indicating this trigeminally evoked brain stem pathway in vitro is endogenously inhibited by mAChRs. Tropicamide, an m4 mAChR antagonist, prevented the inhibitory action of the muscarinic agonist bethanechol. These results indicate that the glutamatergic synaptic neurotransmission in the trigeminally evoked pathway to CVNs is endogenously inhibited in vitro by m4 mAChRs. PMID:20719927

  15. On the Normal Force Mechanotransduction of Human Umbilical Vein Endothelial Cells

    NASA Astrophysics Data System (ADS)

    Vahabikashi, Amir; Wang, Qiuyun; Wilson, James; Wu, Qianhong; Vucbmss Team

    2016-11-01

    In this paper, we report a cellular biomechanics study to examine the normal force mechanotransduction of Human Umbilical Vein Endothelial Cells (HUVECs) with their implications on hypertension. Endothelial cells sense mechanical forces and adjust their structure and function accordingly. The mechanotransduction of normal forces plays a vital role in hypertension due to the higher pressure buildup inside blood vessels. Herein, HUVECs were cultured to full confluency and then exposed to different mechanical loadings using a novel microfluidic flow chamber. One various pressure levels while keeps the shear stress constant inside the flow chamber. Three groups of cells were examined, the control group (neither shear nor normal stresses), the normal pressure group (10 dyne/cm2 of shear stress and 95 mmHg of pressure), and the hypertensive group (10 dyne/cm2 of shear stress and 142 mmHg of pressure). Cellular response characterized by RT-PCR method indicates that, COX-2 expressed under normal pressure but not high pressure; Mn-SOD expressed under both normal and high pressure while this response was stronger for normal pressure; FOS and e-NOS did not respond under any condition. The differential behavior of COX-2 and Mn-SOD in response to changes in pressure, is instrumental for better understanding the pathogenesis of hypertensive cardiovascular diseases. This research was supported by the National Science Foundation under Award #1511096.

  16. Hemicrania continua. Unquestionably a trigeminal autonomic cephalalgia.

    PubMed

    Vincent, Maurice B

    2013-05-01

    Hemicrania continua (HC) is a well-known primary headache. The present version of the International Classification of Headache Disorders lists HC in the "other primary headaches" group. However, evidence has emerged demonstrating that HC is a phenotype that belongs to the trigeminal autonomic cephalalgias together with cluster headache, paroxysmal hemicrania (PH), and short-lasting, unilateral neuralgiform headache attacks with conjunctival injection and tearing. This is supported by a common general clinical picture - paroxysmal, fluctuating, unilateral, side-locked headaches located to the ocular, frontal, and/or temporal regions, accompanied by ipsilateral autonomic dysfunctions including for example, tearing and conjunctival injection. Apart from the remarkable clinical similarities, the absolute and incomparable effect of indomethacin in HC parallels the effect of this drug in PH, suggesting a shared core pathogenesis. Finally, neuroimage findings demonstrate a posterior hypothalamic activation in HC similarly to cluster headache, PH, and short-lasting, unilateral neuralgiform headache attacks with conjunctival injection and tearing. Taken together, data indicate that HC is certainly a type of trigeminal autonomic cephalalgia that should no longer be placed in a group of miscellaneous primary headache disorders.

  17. The usual treatment of trigeminal autonomic cephalalgias.

    PubMed

    Pareja, Juan A; Álvarez, Mónica

    2013-10-01

    Trigeminal autonomic cephalalgias include cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection, tearing, and rhinorrhea (SUNCT). Conventional pharmacological therapy can be successful in the majority of trigeminal autonomic cephalalgias patients. Most cluster headache attacks respond to 100% oxygen inhalation, or 6 mg subcutaneous sumatriptan. Nasal spray of sumatriptan (20 mg) or zolmitriptan (5 mg) are recommended as second choice. The bouts can be brought under control by a short course of corticosteroids (oral prednisone: 60-100 mg/day, or intravenous methylprednisolone: 250-500 mg/day, for 5 days, followed by tapering off the dosage), or by long-term prophylaxis with verapamil (at least 240 mg/day). Alternative long-term preventive medications include lithium carbonate (800-1600 mg/day), methylergonovine (0.4-1.2 mg/day), and topiramate (100-200 mg/day). As a rule, paroxysmal hemicrania responds to preventive treatment with indomethacin (75-150 mg/day). A short course of intravenous lidocaine (1-4 mg/kg/hour) can reduce the flow of attacks during exacerbations of SUNCT. Lamotrigine (100-300 mg/day) is the preventive drug of choice for SUNCT. Gabapentin (800-2700 mg/day), topiramate (50-300 mg/day), and carbamazepine (200-1600 mg/day) may be of help.

  18. Giant Trigeminal Schwannoma Presenting with Obstructive Hydrocephalus

    PubMed Central

    Martinez-Gutierrez, Juan Carlos; Elder, Benjamin D; Olivi, Alessandro

    2015-01-01

    Trigeminal schwannomas represent between 0.07% and 0.36% of all intracranial tumors and 0.8% to 8% of intracranial schwannomas. Selection of the appropriate management strategy requires an understanding of the tumor’s natural history and treatment outcomes. This report describes the case of a 36-year-old male who presented with a three-month history of progressive headaches, dizziness, loss of balance, decreased sleep, and cognitive decline. Magnetic resonance imaging revealed a large enhancing lesion centered around the left Meckel’s cave and extending into both the middle and the posterior fossa with obstructive hydrocephalus secondary to compression of the fourth ventricle. Resection of the posterior fossa component of the tumor was performed in order to relieve the mass effect upon the brainstem without attempting a radical removal of the middle fossa component and a potential risk of further cognitive impairment. The pathological exam confirmed the diagnosis of a trigeminal schwannoma. The residual tumor showed progressive spontaneous volumetric shrinkage after a subtotal surgical resection. This case shows the value of a planned conservative surgery in complex schwannomas and highlights the challenges in interpreting the treatment responses in these benign tumors, whether approached surgically or with stereotactic radiation techniques. PMID:26719829

  19. SCN2B in the Rat Trigeminal Ganglion and Trigeminal Sensory Nuclei.

    PubMed

    Shimada, Yusuke; Sato, Tadasu; Yajima, Takehiro; Fujita, Masatoshi; Hashimoto, Naoya; Shoji, Noriaki; Sasano, Takashi; Ichikawa, Hiroyuki

    2016-11-01

    The beta-2 subunit of the mammalian brain voltage-gated sodium channel (SCN2B) was examined in the rat trigeminal ganglion (TG) and trigeminal sensory nuclei. In the TG, 42.6 % of sensory neurons were immunoreactive (IR) for SCN2B. These neurons had various cell body sizes. In facial skins and oral mucosae, corpuscular nerve endings contained SCN2B-immunoreactivity. SCN2B-IR nerve fibers formed nerve plexuses beneath taste buds in the tongue and incisive papilla. However, SCN2B-IR free nerve endings were rare in cutaneous and mucosal epithelia. Tooth pulps, muscle spindles and major salivary glands were also innervated by SCN2B-IR nerve fibers. A double immunofluorescence method revealed that about 40 % of SCN2B-IR neurons exhibited calcitonin gene-related peptide (CGRP)-immunoreactivity. However, distributions of SCN2B- and CGRP-IR nerve fibers were mostly different in facial, oral and cranial structures. By retrograde tracing method, 60.4 and 85.3 % of TG neurons innervating the facial skin and tooth pulp, respectively, showed SCN2B-immunoreactivity. CGRP-immunoreactivity was co-localized by about 40 % of SCN2B-IR cutaneous and tooth pulp TG neurons. In trigeminal sensory nuclei of the brainstem, SCN2B-IR neuronal cell bodies were common in deep laminae of the subnucleus caudalis, and the subnuclei interpolaris and oralis. In the mesencephalic trigeminal tract nucleus, primary sensory neurons also exhibited SCN2B-immunoreactivity. In other regions of trigeminal sensory nuclei, SCN2B-IR cells were very infrequent. SCN2B-IR neuropil was detected in deep laminae of the subnucleus caudalis as well as in the subnuclei interpolaris, oralis and principalis. These findings suggest that SCN2B is expressed by various types of sensory neurons in the TG. There appears to be SCN2B-containing pathway in the TG and trigeminal sensory nuclei.

  20. Chordin and noggin expression in the adult rat trigeminal nuclei.

    PubMed

    Hayashi, Yutaro; Mikawa, Sumiko; Masumoto, Kazuma; Katou, Fuminori; Sato, Kohji

    2016-12-01

    Bone morphogenetic proteins (BMP) exert its biological functions by interacting with membrane bound receptors. However, functions of BMPs are also regulated in the extracellular space by secreted antagonistic regulators, such as chordin and noggin. Although the deep involvement of BMP signaling in the development and functions of the trigeminal nuclei has been postulated, little information is available for its expression in the trigeminal nuclei. We, thus, investigated chordin and noggin expression in the adult rat trigeminal nuclei using immunohistochemistry. Chordin and noggin were intensely expressed throughout the trigeminal nuclei. In addition, interesting differences are observed between chordin expression and noggin expression. For example, chordin prefers dendritic expression than noggin, suggesting that chordin is involved in the regulation of dendritic morphology and synaptic homeostasis. Furthermore, chordin and noggin were differentially expressed in the neuropil of the trigeminal nuclei. Since BMP signaling is known to play a pivotal role to make precise neural network, theses differences might be important to keep precise interneuronal connections by regulating local BMP signaling intensity in each region. Interestingly, we also detected chordin and noggin expression in axons of the trigeminal nerves. These data indicate that chordin and noggin play pivotal roles also in the adult trigeminal system.

  1. Normalized Metadata Generation for Human Retrieval Using Multiple Video Surveillance Cameras

    PubMed Central

    Jung, Jaehoon; Yoon, Inhye; Lee, Seungwon; Paik, Joonki

    2016-01-01

    Since it is impossible for surveillance personnel to keep monitoring videos from a multiple camera-based surveillance system, an efficient technique is needed to help recognize important situations by retrieving the metadata of an object-of-interest. In a multiple camera-based surveillance system, an object detected in a camera has a different shape in another camera, which is a critical issue of wide-range, real-time surveillance systems. In order to address the problem, this paper presents an object retrieval method by extracting the normalized metadata of an object-of-interest from multiple, heterogeneous cameras. The proposed metadata generation algorithm consists of three steps: (i) generation of a three-dimensional (3D) human model; (ii) human object-based automatic scene calibration; and (iii) metadata generation. More specifically, an appropriately-generated 3D human model provides the foot-to-head direction information that is used as the input of the automatic calibration of each camera. The normalized object information is used to retrieve an object-of-interest in a wide-range, multiple-camera surveillance system in the form of metadata. Experimental results show that the 3D human model matches the ground truth, and automatic calibration-based normalization of metadata enables a successful retrieval and tracking of a human object in the multiple-camera video surveillance system. PMID:27347961

  2. Normalized Metadata Generation for Human Retrieval Using Multiple Video Surveillance Cameras.

    PubMed

    Jung, Jaehoon; Yoon, Inhye; Lee, Seungwon; Paik, Joonki

    2016-06-24

    Since it is impossible for surveillance personnel to keep monitoring videos from a multiple camera-based surveillance system, an efficient technique is needed to help recognize important situations by retrieving the metadata of an object-of-interest. In a multiple camera-based surveillance system, an object detected in a camera has a different shape in another camera, which is a critical issue of wide-range, real-time surveillance systems. In order to address the problem, this paper presents an object retrieval method by extracting the normalized metadata of an object-of-interest from multiple, heterogeneous cameras. The proposed metadata generation algorithm consists of three steps: (i) generation of a three-dimensional (3D) human model; (ii) human object-based automatic scene calibration; and (iii) metadata generation. More specifically, an appropriately-generated 3D human model provides the foot-to-head direction information that is used as the input of the automatic calibration of each camera. The normalized object information is used to retrieve an object-of-interest in a wide-range, multiple-camera surveillance system in the form of metadata. Experimental results show that the 3D human model matches the ground truth, and automatic calibration-based normalization of metadata enables a successful retrieval and tracking of a human object in the multiple-camera video surveillance system.

  3. Staphylococci of the normal human skin flora. Variety of biotypes and antibiograms without direct correlations.

    PubMed

    Hartmann, A A

    1978-05-31

    352 strains of Staphylococci of the normal human skin flora were sampled from one volunteer by single scrabbing in a ca. 3 cm2 measuring area. They were biotyped by the scheme of Pelzer et al.(1973)--a modified Baird-Parker-Scheme (1963)--and the resistance to antibiotics was investigated by the method of Bauer et al. (1966). All the nine biotypes of Staphylococci were found in variable quantities. It seems problematic to call one biotype as the main type. Morphologically identical colonies of Staphylococci from the indigenous flora of the human skin were not identical in their biotypes as previously described by Pelzer (1976). Only the investigation of all Staphylococci colonies from the culture plate can evaluate all biotypes of Staphylococci of the normal human skin flora, and can give the right quantitative correlation. Staphylococci were found to be sensitive and resistant up to four antibiotics, and one biotype did not show one type of antibiogram.

  4. Characterization of midline medulla role in the trigeminal depressor response.

    PubMed

    Clement, M E; McCall, R B

    1989-05-01

    The purpose of the present investigation was to determine the role of the midline medulla in mediating the trigeminal depressor response. Previously we found that lesions of the midline medulla abolished the decrease in blood pressure resulting from electrical stimulation of the spinal trigeminal complex. Electrical stimulation (5 Hz) of the spinal trigeminal tract elicited a decrease in arterial blood pressure that was associated with an inhibition of sympathetic nerve activity recorded from the inferior cardiac nerve of anesthetized cats. The effect of single shocks applied to the trigeminal complex on sympathetic activity was determined using computer-averaging techniques. Single shock stimulation consistently elicited an excitation of sympathetic activity that was followed by an inhibition of sympathetic nerve discharge. The gamma-aminobutyric acid antagonist picrotoxin blocked the depressor response elicited by electrical stimulation of the midline medulla but not by stimulation of the spinal trigeminal complex. Extracellular recordings of the discharges of midline medullary neurons were made to determine the effects of trigeminal stimulation on sympathoinhibitory, sympathoexcitatory, and serotonin neurons. Sympathoinhibitory and sympathoexcitatory neurons were identified by the relationship between unitary discharges and sympathetic nerve activity and by their response to baroreceptor reflex activation. Serotonin (5-HT) neurons were identified using criteria previously developed in our laboratory. These included 1) a slow regular discharge rate, 2) sensitivity to the inhibitory action of the 5-HT1A agonist 8-OH 8-hydroxy-2-(di-n-propylamino)tetralin, 3) failure to respond to baroreceptor reflex activation, and 4) the discharges of the 5-HT neurons were not related to sympathetic activity. Stimulation of the spinal trigeminal complex typically inhibited the discharges of sympathoinhibitory neurons. In contrast, stimulation of the trigeminal complex

  5. Eugenol and carvacrol excite first- and second-order trigeminal neurons and enhance their heat-evoked responses.

    PubMed

    Klein, A H; Joe, C L; Davoodi, A; Takechi, K; Carstens, M I; Carstens, E

    2014-06-20

    Eugenol and carvacrol from clove and oregano, respectively, are agonists of the warmth-sensitive transient receptor potential channel TRPV3 and the irritant-sensitive transient receptor potential ankyrin (TRPA)-1. Eugenol and carvacrol induce oral irritation that rapidly desensitizes, accompanied by brief enhancement of innocuous warmth and heat pain in humans. We presently investigated if eugenol and carvacrol activate nociceptive primary afferent and higher order trigeminal neurons and enhance their heat-evoked responses, using calcium imaging of cultured trigeminal ganglion (TG) and dorsal root ganglion (DRG) neurons, and in vivo single-unit recordings in trigeminal subnucleus caudalis (Vc) of rats. Eugenol and carvacrol activated 20-30% of TG and 7-20% of DRG cells, the majority of which additionally responded to menthol, mustard oil and/or capsaicin. TG cell responses to innocuous (39°) and noxious (42 °C) heating were enhanced by eugenol and carvacrol. We identified dorsomedial Vc neurons responsive to noxious heating of the tongue in pentobarbital-anesthetized rats. Eugenol and carvacrol dose-dependently elicited desensitizing responses in 55% and 73% of heat-sensitive units, respectively. Responses to noxious heat were briefly enhanced by eugenol and carvacrol. Many eugenol- and carvacrol-responsive units also responded to menthol, cinnamaldehyde and capsaicin. These data support a peripheral site for eugenol and carvacrol to enhance warmth- and noxious heat-evoked responses of trigeminal neurons, and are consistent with the observation that these agonists briefly enhance warmth and heat pain on the human tongue.

  6. Eugenol and carvacrol excite first- and second-order trigeminal neurons and enhance their heat-evoked responses

    PubMed Central

    Klein, Amanda H.; Joe, Christopher L.; Davoodi, Auva; Takechi, Kenichi; Carstens, Mirela Iodi; Carstens, E

    2014-01-01

    Eugenol and carvacrol from clove and oregano, respectively, are agonists of the warmth-sensitive transient receptor potential channel TRPV3 and the irritant-sensitive TRPA1. Eugenol and carvacrol induce oral irritation that rapidly desensitizes, accompanied by brief enhancement of innocuous warmth and heat pain in humans. We presently investigated if eugenol and carvacrol activate nociceptive primary afferent and higher-order trigeminal neurons and enhance their heat-evoked responses, using calcium imaging of cultured trigeminal ganglion (TG) and dorsal root ganglion (DRG) neurons, and in vivo single-unit recordings in trigeminal subnucleus caudalis (Vc) of rats. Eugenol and carvacrol activated 20-30% of TG and 7-20% of DRG cells, the majority of which additionally responded to menthol, mustard oil and/or capsaicin. TG cell responses to innocuous (39°) and noxious (42°C) heating were enhanced by eugenol and carvacrol. We identified dorsomedial Vc neurons responsive to noxious heating of the tongue in pentobarbital-anesthetized rats. Eugenol and carvacrol dose-dependently elicited desensitizing responses in 55% and 73% of heat-sensitive units, respectively. Responses to noxious heat were briefly enhanced by eugenol and carvacrol. Many eugenol- and carvacrol-responsive units also responded to menthol, cinnamaldehyde and capsaicin. These data support a peripheral site for eugenol and carvacrol to enhance warmth- and noxious heat-evoked responses of trigeminal neurons, and are consistent with the observation that these agonists briefly enhance warmth and heat pain on the human tongue. PMID:24759772

  7. Substance P/Neurokinin 1 and Trigeminal System: A Possible Link to the Pathogenesis in Sudden Perinatal Deaths

    PubMed Central

    Mehboob, Riffat

    2017-01-01

    Sudden demise of a healthy fetus or a neonate is a very tragic episode in the life of parents. These deaths have been a mystery since ages but still remain unexplained. This review proposes the involvement of trigeminal nerve, neurotransmitter substance P (SP), and its receptor neurokinin 1 (NK-1R) in regulation of cardiorespiratory control in fetuses and newborns. Anomalies and immaturity of neuroregulatory systems such as trigeminal system in medulla oblongata of brainstem may provide a possible mechanism of sudden perinatal deaths. Vulnerable infants are born with respiratory center immaturity which in combination with any stressor such as cold, hypoxia, and smoking may lead to cessation of breathing and ventilatory response. SP/NK-1R may be involved in regulating the ventilatory control in neonates while it is decreased in fetal and adult life in humans, and any alterations from these may lead to irreversible sleep apnea and fatal breathing, ultimately sudden death. This review summarizes the studies performed to highlight the expression of SP or NK-1R in sudden perinatal deaths and proposes the involvement of trigeminal ganglion along with its nerve and SP/NK-1R expression alteration as one of the possible pathophysiological underlying mechanism. However, further studies are required to explore the role of SP, NK-1R, and trigeminal system in the pathogenesis of sudden infant deaths, sudden intrauterine deaths, stillbirths, and sudden deaths later in human life. PMID:28348544

  8. Analysis of structural changes in normal and aneurismal human aortic tissues using FTIR microscopy.

    PubMed

    Rubin, S; Bonnier, F; Sandt, C; Ventéo, L; Pluot, M; Baehrel, B; Manfait, M; Sockalingum, G D

    2008-02-01

    Aortic aneurisms are frequently asymptomatic but can induce dramatic complications. The diagnosis is only based on the aortic diameter and not on a structural and compositional basis. In this preliminary study, we propose infrared microspectroscopy to nondestructively probe normal and aneurismal human aortas. Spectra from 19 human ascending aortic biopsies (10 normal and 9 aneurismal) were acquired using infrared microspectroscopy. A 1500 x 150 microm(2) area of each 7-microm thick cryosection was investigated using a 30-microm spatial resolution with a total of about 200 spectra per sample. Spectral differences between normal and aneurismal tissues were mainly located in spectral regions related to proteins, such as elastin and collagen, and proteoglycans (1750-1000 cm(-1)). Tissue heterogeneity and sample classification have been evaluated using hierarchical cluster analysis of individual or mean spectra and their second derivative. Using spectral range related to proteins, 100% of good classification was obtained whereas the proteoglycan spectral range was less discriminant. This in vitro study demonstrates the potential of such technique to differentiate between normal and aneurismal aortas using selected spectral ranges. Future investigations will be focused on these specific spectral regions to determine the role of elastin and collagen in the discrimination of normal and pathological aortas.

  9. Radioimmunoassay of erythropoietin: circulating levels in normal and polycythemic human beings

    SciTech Connect

    Garcia, J.F.; Ebbe, S.N.; Hollander, L.; Cutting, H.O.; Miller, M.E.; Cronkite, E.P.

    1982-05-01

    Techniques are described in detail for the RIA of human Ep in unextracted plasma or serum. With 100 ..mu..l of sample, the assay is sensitive at an Ep concentration of approximately 4 mU/ml, and when required, the sensitivity can be increased to 0.4 mU/ml, a range considerably less than the concentration observed in normal human beings. This is approximately 100 times more sensitive than existing in vivo bioassays for this hormone. Studies concerned with the validation of the Ep RIA show a high degree of correlation with the polycythemic mouse bioassay. Dilutions of a variety of human serum samples show a parallel relationship with the standard reference preparation for Ep. Validation of the RIA is further confirmed by observations of appropriate increases or decreases of circulating Ep levels in physiological and clinical conditions known to be associated with stimulation or suppression of Ep secretion. Significantly different mean serum concentrations of 17.2 mU/ml for normal male subjects and 18.8 mU/ml for normal female subjects were observed. Mean plasma Ep concentrations in patients with polycythemia vera are significantly decreased, and those of patients with secondary polycythemia are significantly increased as compared to plasma levels in normal subjects. These results demonstrate an initial practical value of the Ep RA in the hematology clinic, which will most certainly be expanded with its more extensive use.

  10. Trigeminal neuralgia secondary to basilar impression: A case report

    PubMed Central

    de Almeida Holanda, Maurus Marques; Pereira Neto, Normando Guedes; de Moura Peixoto, Gustavo; Pinheiro Santos, Rayan Haquim

    2015-01-01

    We report a rare case of trigeminal neuralgia. A 23-year-old woman with a history of 1 year of typical trigeminal neuralgia manifested the characteristics of basilar impression. Magnetic resonance imaging (MRI) demonstrated basilar impression, deformity of the posterior fossa with asymmetry of petrous bone, and compression of medulla oblongata in the topography of the odontoid apophysis. The operation was performed through a suboccipital craniectomy. The neuralgia disappeared after surgery and remains completely resolved until today. This is the second reported case of trigeminal neuralgia in a patient with basilar impression in Brazil. PMID:25972713

  11. Trigeminal neuralgia secondary to basilar impression: A case report.

    PubMed

    de Almeida Holanda, Maurus Marques; Pereira Neto, Normando Guedes; de Moura Peixoto, Gustavo; Pinheiro Santos, Rayan Haquim

    2015-01-01

    We report a rare case of trigeminal neuralgia. A 23-year-old woman with a history of 1 year of typical trigeminal neuralgia manifested the characteristics of basilar impression. Magnetic resonance imaging (MRI) demonstrated basilar impression, deformity of the posterior fossa with asymmetry of petrous bone, and compression of medulla oblongata in the topography of the odontoid apophysis. The operation was performed through a suboccipital craniectomy. The neuralgia disappeared after surgery and remains completely resolved until today. This is the second reported case of trigeminal neuralgia in a patient with basilar impression in Brazil.

  12. Human neural tuning estimated from compound action potentials in normal hearing human volunteers

    NASA Astrophysics Data System (ADS)

    Verschooten, Eric; Desloovere, Christian; Joris, Philip X.

    2015-12-01

    The sharpness of cochlear frequency tuning in humans is debated. Evoked otoacoustic emissions and psychophysical measurements suggest sharper tuning in humans than in laboratory animals [15], but this is disputed based on comparisons of behavioral and electrophysiological measurements across species [14]. Here we used evoked mass potentials to electrophysiologically quantify tuning (Q10) in humans. We combined a notched noise forward masking paradigm [9] with the recording of trans tympanic compound action potentials (CAP) from masked probe tones in awake human and anesthetized monkey (Macaca mulatta). We compare our results to data obtained with the same paradigm in cat and chinchilla [16], and find that CAP-Q10values in human are ˜1.6x higher than in cat and chinchilla and ˜1.3x higher than in monkey. To estimate frequency tuning of single auditory nerve fibers (ANFs) in humans, we derive conversion functions from ANFs in cat, chinchilla, and monkey and apply these to the human CAP measurements. The data suggest that sharp cochlear tuning is a feature of old-world primates.

  13. Antiapoptotic effects of estrogen in normal and cancer human cervical epithelial cells.

    PubMed

    Wang, Qifang; Li, Xin; Wang, Liqin; Feng, Ying-Hong; Zeng, Robin; Gorodeski, George

    2004-12-01

    The present study investigated the antiapoptotic effects of estrogen in normal and cancer human cervical cells and the mechanisms involved. Baseline apoptosis in human cervical epithelial cells is mediated predominantly by P2X7-receptor-induced, Ca(2+)-dependent activation of the mitochondrial (caspase-9) pathway. Treatment with 10 nM 17beta-estradiol blocked apoptosis induced by the P2X7-receptor ligands ATP and 2',3'-0-(4-benzoylbenzoyl)-ATP in normal human cervical epithelial cells (hECEs) and attenuated the effect in hECEs immortalized with human papillomavirus-16 (ECE16-1) and the cancer cervical cells HT3 and CaSki. Diethylstilbestrol and to a lesser degree estrone could mimic the effects of 17beta-estradiol, whereas actinomycin-D and cycloheximide attenuated the response. The antiapoptotic effect of estrogen did not depend on cell cycle phase, and in both normal and cancer cervical cells, it involved attenuation of activation of caspase-9 and the terminal caspase-3. However, involvement of cascades upstream to the caspase-9 differed in normal vs. cancer cervical cells. In the normal hECEs estrogen blocked P2X7-receptor-induced calcium influx. In contrast, in the cancer CaSki cells, estrogen up-regulated expression of Bcl-2 and attenuated Ca(2+)-induced mitochondrial swelling (i.e. formation of mitochondrial permeability transition pores). Estrogen had no effect on P2X7-receptor-induced apoptosis in the anaplastic SiHa and Hela cells. These results point to a novel antiapoptotic effect of estrogen in the cervix that is independent of its mitogenic function. The results also suggest that cancer cervical cells evolved antiapoptotic mechanisms that enable the cells to evade apoptosis and could therefore promote tumor progression.

  14. Radiographic Comparison of Human Lung Shape During Normal Gravity and Weightlessness

    NASA Technical Reports Server (NTRS)

    Michels, D. B.; Friedman, P. J.; West, J. B.

    1979-01-01

    Chest radiographs in five seated normal volunteers at 1 G and 0 G were made with a view toward comparing human lung shape during normal gravity and weightlessness. Lung shape was assessed by measuring lung heights and widths in upper, middle and lower lung regions. No significant differences were found between any of the 1-G and 0-G measurements, although there was a slight tendency for the lung to become shorter and wider at 0 G. The evidence that gravity causes regional differences in ventilation by direct action on the lung is consistent with the theoretical analysis of West and Matthews (1972).

  15. Three-Dimensional Normal Human Neutral Progenitor Tissue-Like Assemblies: A Model for Persistent Varicella-Zoster Virus Infection and Platform to Study Oxidate Stress and Damage in Multiple Hit Scenarios

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas J.; McCarthy, M.; Osterrieder, N.; Cohrs, R. J.; Kaufer, B. B.

    2014-01-01

    The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpes virus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex three-dimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6]. By combining the RFs of microgravity, radiation, and viral infection we will demonstrate that living in the space environment leads to significant physiological consequences for the peripheral and subsequently the central nervous system (PNS, CNS) associated with OSaD generation and consequentially endangers long-duration and exploration-class missions.

  16. Low calcium culture condition induces mesenchymal cell-like phenotype in normal human epidermal keratinocytes

    SciTech Connect

    Takagi, Ryo; Yamato, Masayuki; Murakami, Daisuke; Sugiyama, Hiroaki; Okano, Teruo

    2011-08-26

    Highlights: {yields} Normal human epidermal keratinocytes serially cultured under low calcium concentration were cytokeratin and vimentin double positive cells. {yields} The human keratinocytes expressed some epithelial stem/progenitor cell makers, mesenchymal cell markers, and markers of epithelial-mesenchymal transition. {yields} Mesenchymal cell-like phenotype in the keratinocytes was suppressed under high-calcium condition. -- Abstract: Epithelial-mesenchymal transition (EMT) is an important cellular phenomenon in organ developments, cancer invasions, and wound healing, and many types of transformed cell lines are used for investigating for molecular mechanisms of EMT. However, there are few reports for EMT in normal human epithelial cells, which are non-transformed or non-immortalized cells, in vitro. Therefore, normal human epidermal keratinocytes (NHEK) serially cultured in low-calcium concentration medium (LCM) were used for investigating relations between differentiation and proliferation and mesenchymal-like phenotype in the present study, since long-term cultivation of NHEK is achieved in LCM. Interestingly, NHEK serially cultured in LCM consisted essentially of cytokeratin-vimentin double positive cells (98%), although the NHEK exhibited differentiation under high-calcium culture condition with 3T3 feeder layer. The vimentin expression was suppressed under high-calcium condition. These results may indicate the importance of mesenchymal-like phenotype for serially cultivation of NHEK in vitro.

  17. New Insights in Trigeminal Anatomy: A Double Orofacial Tract for Nociceptive Input

    PubMed Central

    Henssen, Dylan J. H. A.; Kurt, Erkan; Kozicz, Tamas; van Dongen, Robert; Bartels, Ronald H. M. A.; van Cappellen van Walsum, Anne-Marie

    2016-01-01

    Orofacial pain in patients relies on the anatomical pathways that conduct nociceptive information, originating from the periphery towards the trigeminal sensory nucleus complex (TSNC) and finally, to the thalami and the somatosensorical cortical regions. The anatomy and function of the so-called trigeminothalamic tracts have been investigated before. In these animal-based studies from the previous century, the intracerebral pathways were mapped using different retro- and anterograde tracing methods. We review the literature on the trigeminothalamic tracts focusing on these animal tracer studies. Subsequently, we related the observations of these studies to clinical findings using fMRI trials. The intracerebral trigeminal pathways can be subdivided into three pathways: a ventral (contralateral) and dorsal (mainly ipsilateral) trigeminothalamic tract and the intranuclear pathway. Based on the reviewed evidence we hypothesize the co-existence of an ipsilateral nociceptive conduction tract to the cerebral cortex and we translate evidence from animal-based research to the human anatomy. Our hypothesis differs from the classical idea that orofacial pain arises only from nociceptive information via the contralateral, ventral trigeminothalamic pathway. Better understanding of the histology, anatomy and connectivity of the trigeminal fibers could contribute to the discovery of a more effective pain treatment in patients suffering from various orofacial pain syndromes. PMID:27242449

  18. A radioimmunoassay for erythropoietin: serum levels in normal human subjects and patients with hemopoietic disorders

    SciTech Connect

    Rege, A.B.; Brookins, J.; Fisher, J.W.

    1982-12-01

    An RIA for Ep has been developed that is highly sensitive and specific. A homogeneous Ep preparation was labeled with /sup 125/I by the chloramine-T method to a specific activity of 90 to 136 ..mu..Ci/..mu..g and immunoreactivity of 80%. Ep antiserum, which was produced to a human urinary Ep preparation (80 U/mg of protein), was adsorbed with normal human urinary and serum proteins without any loss in sensitivity of the RIA to increase the specificity of the assay. A good correlation was seen between the RIA and the exhypoxic polycythemic mouse assay (corr. coef. 0.967; slope 1.05 and ''y'' intercept 0.75). Ep titers in sera from 175 hematologically normal human subjects exhibited a normal frequency distribution and ranged between 5.8 and 36.6 mU/ml with a mean of 14.9 +/- 4.7 (S.D.) and median of 14.3. Serum Ep titers were markedly elevated in seven patients with aplastic anemia and one patient with pure red cell aplasia (1350 to 20,640 mU/ml) and were lower than normal in two patients with polycythemia vera (8.1 and 9.4 mU/ml). The serum Ep titers in a prenephrectomy patient with chronic glomerulonephritis (31.1 mU/ml) decreased to below normal levels (9.04 mU/ml) after nephrectomy. The cord serum erythropoietin titers in 10 IDM (90.82 +/- 134.1 (S.D.) mu/ml) returned to values within the normal range (13.86 +/- 5.55) on day 3 after birth, suggesting the utility of the RIA in elucidating the role of hypoxia and/or insulin in increased erythropoiesis in IDM. The serum Ep titers in patients with anemias and polycythemias were compared to those of normal human subjects and agreed well with pathophysiologic mechanisms of these hemopoietic disorders, confirming the validity of the RIA.

  19. A radioimmunoassay for erythropoietin: serum levels in normal human subjects and patients with hemopoietic disorders

    SciTech Connect

    Rege, A.B.; Brookins, J.; Fisher, J.W.

    1982-12-01

    An RIA for Ep has been developed that is highly sensitive and specific. A homogeneous Ep preparation was labeled with /sup 125/I by the chloramine-T method to a specific activity of 90 to 136 micro Ci/microgram and immunoreactivity of 80%. Ep antiserum, which was produced to a human urinary Ep preparation (80 U/mg of protein), was adsorbed with normal human urinary and serum proteins without any loss in sensitivity of the RIA to increase the specificity of the assay. A good correlation was seen between the RIA and the exhypoxic polycythemic mouse assay (corr. coef. 0.967; slope 1.05 and y intercept 0.75). Ep titers in sera from 175 hematologically normal human subjects exhibited a normal frequency distribution and ranged between 5.8 and 36.6 mU/ml with a mean of 14.9 +/- 4.7 (S.D.) and median of 14.3 Serum Ep titers were markedly elevated in seven patients with aplastic anemia and one patient with pure red cell aplasia (1350 to 20,640 mU/ml) and were lower than normal in two patients with polycythemia vera (8.1 and 9.4 mU/ml). The serum Ep titers in a prenephrectomy patient with chronic glomerulonephritis (32.1 mU/ml) decreased to below normal levels (9.04 mU/ml) after nephrectomy. The cord serum erythropoietin titers in 10 IDM (90.82 +/- 134.1 (S.D.) mu/ml) returned to values within the normal range (13.86 +/- 5.55) on day 3 after birth, suggesting the utility of the RIA in elucidating the role of hypoxia and/or insulin in increased erythropoiesis in IDM. The serum Ep titers in patients with anemias and polycythemias were compared to those of normal human subjects and agreed well with pathophysiologic mechanisms of these hemopoietic disorders, confirming the validity of the RIA.

  20. Ethanolic Extracts of California Mugwort (Artemisia douglasiana Besser) Are Cytotoxic against Normal and Cancerous Human Cells

    PubMed Central

    Somaweera, Himali; Lai, Gary C.; Blackeye, Rachel; Littlejohn, Beverly; Kirksey, Justine; Aguirre, Richard M.; LaPena, Vince; Pasqua, Anna; Hintz, Mary McCarthy

    2013-01-01

    California mugwort (Artemisia douglasiana Besser) is used by many tribes throughout California to treat a variety of conditions, including colds, allergies, and pain. California mugwort is also utilized as women’s medicine. Its use is on the rise outside of Native communities, often without the guidance of a traditional healer or experienced herbalist. Because it has been shown to have antiproliferative activity against plant and animal cells, we investigated whether California mugwort extracts have an effect on normal human cells as well as estrogen receptor positive (ER+) and estrogen receptor negative (ER−) human breast cancer cells. Ethanolic and aqueous extracts of A. douglasiana leaves were tested for cytotoxicity against unstimulated normal human peripheral blood mononuclear cells (hPBMC), as well as against an ER+ human breast cancer cell line (BT-474) and an ER− human breast cancer cell line (MDA-MB-231). An ethanolic leaf extract killed hPBMC, BT-474, and MDA-MB-231 cells with IC50 values of 23.6 ± 0.3, 27 ± 5, and 37 ± 4 μg/ml, respectively. An aqueous extract killed hPBMC with an IC50 value of 60 ± 10 μg/ml, but had no effect on the two cancer cell lines at concentrations up to 100 μg/ml. The results of this study indicate that the cytotoxicity of California mugwort extends to normal human cells, as well as cancerous cells. Therefore, until further is known about the safety of this medicine, caution should be taken when consuming extracts of California mugwort, whether as a tincture or as a tea. PMID:24073389

  1. FTIR microscopic comparative study on normal, premalignant, and malignant tissues of human intenstine

    NASA Astrophysics Data System (ADS)

    Mordechai, Shaul; Argov, Shmuel; Salman, Ahmad O.; Cohen, Beny; Ramesh, Jagannathan; Erukhimovitch, Vitaly; Goldstein, Jed; Sinelnikov, Igor

    2000-07-01

    Fourier-Transform Infrared Spectroscopy (FTIR) employs a unique approach to optical diagnosis of tissue pathology based on the characteristic molecular vibrational spectra of the tissue. The architectural changes in the cellular and sub-cellular levels developing in abnormal tissue, including a majority of cancer forms, manifest themselves in different optical signatures, which can be detected in infrared spectroscopy. The biological systems we have studied include normal, premalignant (polyp) and malignant human colonic tissues from three patients. Our method is based on microscopic infrared study (FTIR-microscopy) of thin tissue specimens and a direct comparison with normal histopathological analysis, which serves as a `gold' reference. The normal intestine tissue has a stronger absorption than polyp and cancerous types over a wide region in all three cases. The detailed analysis showed that there is a significant decrease in total phosphate and creatine contents for polyp and cancerous tissue types in comparison to the controls.

  2. Analysis of normal human eye with different age groups using infrared images.

    PubMed

    Acharya, U Rajendra; Ng, E Y K; Yee, Gerk Chang; Hua, Tan Jian; Kagathi, Manjunath

    2009-06-01

    The human body temperature is a good health indicator. All objects emit thermal radiation as a function temperature and wavelength for all wavelengths. The wavelength of infrared rays lies between visible and microwave radiations ranging between 700 nm to 0.1 mm. Infrared (IR) imaging is relatively inexpensive, noninvasive and harmless. Nowadays, it is widely used in the medical field for diagnosis. In this work, we have applied image processing techniques on the IR images of the eye for the analysis of the ocular surface temperature (OST) of the normal subjects of three categories (young, middle and old ages). In our study, 67 IR normal images were analyzed. Two parameters, average ocular temperature and the temperature deviation were proposed to study the variability of OST in different normal category subjects. Our study shows that, the two parameters proposed, show distinct ranges for different groups with 'p' values less than 0.05.

  3. Low prevalence of high risk human papillomavirus in normal oral mucosa by hybrid capture 2

    PubMed Central

    González-Losa, Maria del Refugio; Manzano-Cabrera, Luis; Rueda-Gordillo, Florencio; Hernández-Solís, Sandra E.; Puerto-Solís, Luis

    2008-01-01

    High risk human papillomavirus (HR-HPV) are recognized as a necessary factor to development cervical cancer. During the last decade many studies have found HR-HPV in oral squamous cell carcinoma (OSCC) and normal oral mucosa, however the association between HR-HPV and OSCC is still uncertain. The aim of the study was to determine DNA HR-HPV in normal oral cavity of healthy adults. A cross-sectional study was performed; samples from 77 patients with normal oral cavity were collected at the Dentistry school, Autonomous University of Yucatan, Merida, Yucatan, México. HR-HPV was detected by hybrid capture 2. One sample out of 77(1.2%) was positive for HR-PVH. It was from a man of 50 years old. HRHPV is present in low rate among healthy oral mucosa. Hybrid capture 2 could be a good methodology for large epidemiology studies. PMID:24031173

  4. Immediate induction of heat shock proteins is not protective against cryopreservation in normal human fibroblasts.

    PubMed

    Park, S J; Choi, H R; Nam, K M; Na, J I; Huh, C H; Park, K C

    2013-01-01

    Heat shock proteins (HSPs) were first identified as proteins whose synthesis was enhanced by stresses, such as increased temperature. HSPs can protect cells from various cytotoxic factors by stabilizing proteins. Thus, it could be hypothesized that heat induced HSPs can provide protective effects against cryopreservation-induced cell death. The aim of this study was to determine whether induction of HSPs can increase the cell viability of normal human fibroblasts after cryopreservation. Cytotoxic effects of heat treatment were tested and the induction of HSPs was assessed by examining time-dependent HSP expression. A cell counting method using fluorescence microscopy was used to determine the viability of cells. In addition, the effects of geranylgeranylacetone were evaluated in terms of HSP expression and cytoskeleton changes. The results of this study showed that immediate induction of HSPs does not protect normal human fibroblasts against cryopreservation-induced cell death possibly by inducing cytoskeleton changes.

  5. Scattering properties of normal and cancerous tissues from human stomach based on phase-contrast microscope

    NASA Astrophysics Data System (ADS)

    Zhang, Hui; Li, Zhifang; Li, Hui

    2012-12-01

    In order to study scattering properties of normal and cancerous tissues from human stomach, we collect images for human gastric specimens by using phase-contrast microscope. The images were processed by the way of mathematics morphology. The equivalent particle size distribution of tissues can be obtained. Combining with Mie scattering theory, the scattering properties of tissues can be calculated. Assume scattering of light in biological tissue can be seen as separate scattering events by different particles, total scattering properties can be equivalent to as scattering sum of particles with different diameters. The results suggest that scattering coefficient of the cancerous tissue is significantly higher than that of normal tissue. The scattering phase function is different especially in the backscattering area. Those are significant clinical benefits to diagnosis cancerous tissue

  6. System parameters for erythropoiesis control model: Comparison of normal values in human and mouse model

    NASA Technical Reports Server (NTRS)

    1979-01-01

    The computer model for erythropoietic control was adapted to the mouse system by altering system parameters originally given for the human to those which more realistically represent the mouse. Parameter values were obtained from a variety of literature sources. Using the mouse model, the mouse was studied as a potential experimental model for spaceflight. Simulation studies of dehydration and hypoxia were performed. A comparison of system parameters for the mouse and human models is presented. Aside from the obvious differences expected in fluid volumes, blood flows and metabolic rates, larger differences were observed in the following: erythrocyte life span, erythropoietin half-life, and normal arterial pO2.

  7. Gamma Knife® radiosurgery for trigeminal neuralgia.

    PubMed

    Yen, Chun-Po; Schlesinger, David; Sheehan, Jason P

    2011-11-01

    Trigeminal neuralgia is characterized by a temporary paroxysmal lancinating facial pain in the trigeminal nerve distribution. The prevalence is four to five per 100,000. Local pressure on nerve fibers from vascular loops results in painful afferent discharge from an injured segment of the fifth cranial nerve. Microvascular decompression addresses the underlying pathophysiology of the disease, making this treatment the gold standard for medically refractory trigeminal neuralgia. In patients who cannot tolerate a surgical procedure, those in whom a vascular etiology cannot be identified, or those unwilling to undergo an open surgery, stereotactic radiosurgery is an appropriate alternative. The majority of patients with typical facial pain will achieve relief following radiosurgical treatment. Long-term follow-up for recurrence as well as for radiation-induced complications is required in all patients undergoing stereotactic radiosurgery for trigeminal neuralgia.

  8. Update on neuropathic pain treatment for trigeminal neuralgia

    PubMed Central

    Al-Quliti, Khalid W.

    2015-01-01

    Trigeminal neuralgia is a syndrome of unilateral, paroxysmal, stabbing facial pain, originating from the trigeminal nerve. Careful history of typical symptoms is crucial for diagnosis. Most cases are caused by vascular compression of the trigeminal root adjacent to the pons leading to focal demyelination and ephaptic axonal transmission. Brain imaging is required to exclude secondary causes. Many medical and surgical treatments are available. Most patients respond well to pharmacotherapy; carbamazepine and oxcarbazepine are first line therapy, while lamotrigine and baclofen are considered second line treatments. Other drugs such as topiramate, levetiracetam, gabapentin, pregabalin, and botulinum toxin-A are alternative treatments. Surgical options are available if medications are no longer effective or tolerated. Microvascular decompression, gamma knife radiosurgery, and percutaneous rhizotomies are most promising surgical alternatives. This paper reviews the medical and surgical therapeutic options for the treatment of trigeminal neuralgia, based on available evidence and guidelines. PMID:25864062

  9. Apoptosis in human chorionic villi and decidua in normal and ectopic pregnancy.

    PubMed

    Kokawa, K; Shikone, T; Nakano, R

    1998-01-01

    To investigate possible effects of implantation on apoptosis, we examined the cleavage of DNA in human chorionic villi and decidua in intrauterine and ectopic pregnancy. Very limited but detectable cleavage of DNA was recognized in the chorionic villi and decidua in normal pregnancy. A ladder pattern, characteristic of the apoptotic breakdown of DNA, was present in the villi in tubal pregnancy. High molecular weight DNA was predominant in the decidua in tubal pregnancy. Quantitative analysis of low molecular weight fragments of DNA revealed a significant increase in the villous tissue, together with a significant decrease in the decidual tissue, in tubal pregnancy as compared to those in normal pregnancy. An analysis in situ revealed that apoptotic cells were predominant in the syncytiotrophoblast in tubal pregnancy. In decidual tissue, labelled cells were occasionally seen in normal pregnancy, and their numbers decreased in tubal pregnancy. The present study demonstrates that apoptosis occurs in the villi, but not in the decidua in tubal pregnancy, unlike the situation in normal pregnancy. Our results suggest that the implantation site might affect the occurrence of apoptotic changes in early pregnancy of humans.

  10. Polymorphism of the long-wavelength cone in normal human colour vision

    NASA Astrophysics Data System (ADS)

    Neitz, Jay; Jacobs, Gerald H.

    1986-10-01

    Colour vision is based on the presence of multiple classes of cone each of which contains a different type of photopigment1. Colour matching tests have long revealed that the normal human has three cone types. Results from these tests have also been used to provide estimates of cone spectral sensitivities2. There are significant variations in colour matches made by individuals whose colour vision is classified as normal3-6. Some of this is due to individual differences in preretinal absorption and photopigment density, but some is also believed to arise because there is variation in the spectral positioning of the cone pigments among those who have normal colour vision. We have used a sensitive colour matching test to examine the magnitude and nature of this individual variation and here report evidence for the existence of two different long-wavelength cone mechanisms in normal humans. The different patterns of colour matches made by male and female subjects indicate these two mechanisms are inherited as an X-chromosome linked trait.

  11. Normalizing and scaling of data to derive human response corridors from impact tests.

    PubMed

    Yoganandan, Narayan; Arun, Mike W J; Pintar, Frank A

    2014-06-03

    It is well known that variability is inherent in any biological experiment. Human cadavers (Post-Mortem Human Subjects, PMHS) are routinely used to determine responses to impact loading for crashworthiness applications including civilian (motor vehicle) and military environments. It is important to transform measured variables from PMHS tests (accelerations, forces and deflections) to a standard or reference population, termed normalization. The transformation process should account for inter-specimen variations with some underlying assumptions used during normalization. Scaling is a process by which normalized responses are converted from one standard to another (example, mid-size adult male to large-male and small-size female adults, and to pediatric populations). These responses are used to derive corridors to assess the biofidelity of anthropomorphic test devices (crash dummies) used to predict injury in impact environments and design injury mitigating devices. This survey examines the pros and cons of different approaches for obtaining normalized and scaled responses and corridors used in biomechanical studies for over four decades. Specifically, the equal-stress equal-velocity and impulse-momentum methods along with their variations are discussed in this review. Methods ranging from subjective to quasi-static loading to different approaches are discussed for deriving temporal mean and plus minus one standard deviation human corridors of time-varying fundamental responses and cross variables (e.g., force-deflection). The survey offers some insights into the potential efficacy of these approaches with examples from recent impact tests and concludes with recommendations for future studies. The importance of considering various parameters during the experimental design of human impact tests is stressed.

  12. Human cytokine responses induced by Gram-positive cell walls of normal intestinal microbiota

    PubMed Central

    Chen, T; Isomäki, P; Rimpiläinen, M; Toivanen, P

    1999-01-01

    The normal microbiota plays an important role in the health of the host, but little is known of how the human immune system recognizes and responds to Gram-positive indigenous bacteria. We have investigated cytokine responses of peripheral blood mononuclear cells (PBMC) to Gram-positive cell walls (CW) derived from four common intestinal indigenous bacteria, Eubacterium aerofaciens (Eu.a.), Eubacterium limosum(Eu.l.), Lactobacillus casei(L.c.), and Lactobacillus fermentum (L.f.). Our results indicate that Gram-positive CW of the normal intestinal microbiota can induce cytokine responses of the human PBMC. The profile, level and kinetics of these responses are similar to those induced by lipopolysaccharide (LPS) or CW derived from a pathogen, Streptococcus pyogenes (S.p.). Bacterial CW are capable of inducing production of a proinflammatory cytokine, tumour necrosis factor-alpha (TNF-α), and an anti-inflammatory cytokine, IL-10, but not that of IL-4 or interferon-gamma (IFN-γ). Monocytes are the main cell population in PBMC to produce TNF-α and IL-10. Induction of cytokine secretion is serum-dependent; both CD14-dependent and -independent pathways are involved. These findings suggest that the human cytokine responses induced by Gram-positive CW of the normal intestinal microbiota are similar to those induced by LPS or Gram-positive CW of the pathogens. PMID:10540188

  13. Hemimasticatory spasm treated with microvascular decompression of the trigeminal nerve.

    PubMed

    Chon, Kyu-Hyon; Lee, Jong-Myong; Koh, Eun-Jeong; Choi, Ha-Young

    2012-09-01

    Hemimasticatory spasm is a very rare disorder of the trigeminal nerve characterized by paroxysmal involuntary contraction of the jaw-closing muscles. The mechanisms leading to hemimasticatory spasm are still unclear. Recently, injection of botulinum toxin has become the treatment of choice due to its excellent results. We report a case of a successful treatment of hemimasticatory spasm via microvascular decompression of the motor branch of the trigeminal nerve.

  14. The distribution and expression of the Bloom's syndrome gene product in normal and neoplastic human cells.

    PubMed

    Turley, H; Wu, L; Canamero, M; Gatter, K C; Hickson, I D

    2001-07-20

    Bloom's syndrome (BS) is an autosomal recessive disorder associated with a predisposition to cancers of all types. Cells from BS sufferers display extreme genomic instability. The BS gene product, BLM, is a 159 kDa DNA helicase enzyme belonging to the RecQ family. Here, we have analysed the distribution of BLM in normal and tumour tissues from humans using a recently characterized, specific monoclonal antibody. BLM was found to be localized to nuclei in normal lymphoid tissues, but was largely absent from other normal tissues analysed with the exception of the proliferating compartment of certain tissues. In contrast, expression of BLM was observed in a variety of tumours of both lymphoid and epithelial origin. A strong correlation was observed between expression of BLM and the proliferative status of cells, as determined by staining for markers of cell proliferation (PCNA and Ki67). We conclude that BLM is a proliferation marker in normal and neoplastic cells in vivo, and, as a consequence, is expressed at a higher level in tumours than in normal quiescent tissues.

  15. Spatial variability of muscle activity during human walking: the effects of different EMG normalization approaches.

    PubMed

    Cronin, N J; Kumpulainen, S; Joutjärvi, T; Finni, T; Piitulainen, H

    2015-08-06

    Human leg muscles are often activated inhomogeneously, e.g. in standing. This may also occur in complex tasks like walking. Thus, bipolar surface electromyography (sEMG) may not accurately represent whole muscle activity. This study used 64-electrode high-density sEMG (HD-sEMG) to examine spatial variability of lateral gastrocnemius (LG) muscle activity during the stance phase of walking, maximal voluntary contractions (MVCs) and maximal M-waves, and determined the effects of different normalization approaches on spatial and inter-participant variability. Plantar flexion MVC, maximal electrically elicited M-waves and walking at self-selected speed were recorded in eight healthy males aged 24-34. sEMG signals were assessed in four ways: unnormalized, and normalized to MVC, M-wave or peak sEMG during the stance phase of walking. During walking, LG activity varied spatially, and was largest in the distal and lateral regions. Spatial variability fluctuated throughout the stance phase. Normalizing walking EMG signals to the peak value during stance reduced spatial variability within LG on average by 70%, and inter-participant variability by 67%. Normalizing to MVC reduced spatial variability by 17% but increased inter-participant variability by 230%. Normalizing to M-wave produced the greatest spatial variability (45% greater than unnormalized EMG) and increased inter-participant variability by 70%. Unnormalized bipolar LG sEMG may provide misleading results about representative muscle activity in walking due to spatial variability. For the peak value and MVC approaches, different electrode locations likely have minor effects on normalized results, whereas electrode location should be carefully considered when normalizing walking sEMG data to maximal M-waves.

  16. Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor tissues.

    PubMed

    Cordon-Cardo, C; O'Brien, J P; Boccia, J; Casals, D; Bertino, J R; Melamed, M R

    1990-09-01

    We have characterized the normal human tissue distribution and tumor expression of the human multidrug resistance gene (MDR1) product P-glycoprotein (Pgp) by immunohistochemical staining of frozen tissue sections of human normal and tumor tissues, using three mouse monoclonal antibodies (MAb) which recognize at least two different epitopes of Pgp. Pgp expression on normal human tissues was detected in specialized epithelial cells with secretory/excretory functions, trophoblasts in the placenta, and on endothelial cells of capillary blood vessels at blood-tissue barrier sites. There were significant differences in the staining patterns of these MAb. Mouse MAb HYB-241 and HYB-612 each recognize an extracellular epitope of Pgp, whereas mouse MAb C219 detects a carboxy terminal intracellular epitope and has recently been reported to crossreact with the MDR3 gene product. HYB-241 and HYB-612 strongly stain endothelial cells and trophoblasts, whereas C219 is weakly positive or unreactive on these cells. Likewise, C219 strongly stains the biliary pole of hepatocytes, skeletal and heart muscle fibers, whereas HYB-241 and HYB-612 are unreactive on these cells. Immunopathological studies were performed on a wide variety of human tumors. Pgp expression on human tumors was most commonly detected in colon. renal, and adrenal carcinomas; rarely in lung and gastric carcinomas and certain germ cell tumors; and was undetectable in breast and endometrial carcinomas tested. Few sarcomas and none of the melanomas, neuroblastomas, gliomas, and pheochromocytomas had detectable Pgp expression. Intensity and pattern of staining varied among different cases of a given tumor type; although homogeneous immunoreactivity was observed, heterogeneity of expression in a single histological section was more common. The finding of Pgp expression in a variety of normal tissues with diverse physiological functions suggests that the role of Pgp may not be limited to excretion of xenobiotics. Pgp

  17. Imaging of Keratoconic and normal human cornea with a Brillouin imaging system (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Besner, Sebastien; Shao, Peng; Scarcelli, Giuliano; Pineda, Roberto; Yun, Seok-Hyun (Andy)

    2016-03-01

    Keratoconus is a degenerative disorder of the eye characterized by human cornea thinning and morphological change to a more conical shape. Current diagnosis of this disease relies on topographic imaging of the cornea. Early and differential diagnosis is difficult. In keratoconus, mechanical properties are found to be compromised. A clinically available invasive technique capable of measuring the mechanical properties of the cornea is of significant importance for understanding the mechanism of keratoconus development and improve detection and intervention in keratoconus. The capability of Brillouin imaging to detect local longitudinal modulus in human cornea has been demonstrated previously. We report our non-contact, non-invasive, clinically viable Brillouin imaging system engineered to evaluate mechanical properties human cornea in vivo. The system takes advantage of a highly dispersive 2-stage virtually imaged phased array (VIPA) to detect weak Brillouin scattering signal from biological samples. With a 1.5-mW light beam from a 780-nm single-wavelength laser source, the system is able to detect Brillouin frequency shift of a single point in human cornea less than 0.3 second, at a 5μm/30μm lateral/axial resolution. Sensitivity of the system was quantified to be ~ 10 MHz. A-scans at different sample locations on a human cornea with a motorized human interface. We imaged both normal and keratoconic human corneas with this system. Whereas no significantly difference were observed outside keratocnic cones compared with normal cornea, a highly statistically significantly decrease was found in the cone regions.

  18. Anti-galactose antibodies do not bind to normal human red cells

    SciTech Connect

    Kay, M.M.B.; Bosman, G.J.C.G.M.

    1986-03-01

    The authors investigated the possibility that senescent cell IgG might have an anti-galactose (anti-gal) specificity as suggested by others. Anti-gal was isolated from normal human serum with ..cap alpha.. melibiose-agarose. The assays used were hemagglutination, rosetting, phagocytosis, and /sup 125/I protein A binding assay, immunoblotting, and glycine/HCL, pH 2.3, versus sugar elutions. Results revealed binding of anti-gal to rabbit but not human RBC. Immunoblotting of anti-gal revealed labeling of approx.29 bands in rabbit red cell membranes and no labeling of autologous human red cell membranes. The authors attempted to inhibit binding of anti-gal with various sugars. Melibiose caused enhancement rather than inhibition of agglutination when used at concentrations reported by previous investigators to cause inhibition. Neither ..cap alpha.. melibiose or galactose caused inhibition of phagocytosis of senescent cells. Senescent cell IgG was not displaced from freshly isolated old red cells by incubation with melibiose or galactose as determined by an /sup 125/I protein A binding assay. The authors were also unable to elute IgG from stored red cells with galactose. The authors conclude that senescent cell IgG does not have an anti-galactose specificity. The authors were unable to demonstrate an anti-gal antibody to normal human red cells.

  19. Distribution of somatostatin receptors in normal and neoplastic human tissues: recent advances and potential relevance.

    PubMed

    Reubi, J C; Schaer, J C; Markwalder, R; Waser, B; Horisberger, U; Laissue, J

    1997-01-01

    This short review describes the localization of somatostatin receptors with in vitro receptor autoradiography techniques in several non-classical, normal human somatostatin target tissues as well as in selected human tumors. In addition to brain, gut and neuroendocrine localizations, somatostatin receptors are expressed in most lymphatic tissues, including gut-associated lymphatic tissue, spleen and thymus; in the cortical and medullary area of the kidney; in the stroma of the prostate and in the epithelial cells of the thyroid. Among human tumors, the extremely high density of somatostatin receptors in medulloblastomas should be stressed as well as the favorable prognostic role of the presence of somatostatin receptors in neuroblastomas. Moreover, several types of mesenchymal tumors have somatostatin receptors as well. The receptor subtypes expressed by distinct tumors may vary: Whereas medulloblastomas and neuroblastomas predominantly express sst2, prostate cancers express sst1 rather than sst2. A further emerging somatostatin target is represented by the peritumoral veins, also known to express sst2 receptors. The multiple somatostatin targets in normal and pathological human tissues represents the basis for potential diagnostic and clinical applications of somatostatin analogs.

  20. PARP Inhibitors in Clinical Use Induce Genomic Instability in Normal Human Cells

    PubMed Central

    Ito, Shuhei; Murphy, Conleth G.; Doubrovina, Ekaterina; Jasin, Maria; Moynahan, Mary Ellen

    2016-01-01

    Poly(ADP-ribose) polymerases (PARPs) are the first proteins involved in cellular DNA repair pathways to be targeted by specific inhibitors for clinical benefit. Tumors harboring genetic defects in homologous recombination (HR), a DNA double-strand break (DSB) repair pathway, are hypersensitive to PARP inhibitors (PARPi). Early phase clinical trials with PARPi have been promising in patients with advanced BRCA1 or BRCA2-associated breast, ovary and prostate cancer and have led to limited approval for treatment of BRCA-deficient ovary cancer. Unlike HR-defective cells, HR-proficient cells manifest very low cytotoxicity when exposed to PARPi, although they mount a DNA damage response. However, the genotoxic effects on normal human cells when agents including PARPi disturb proficient cellular repair processes have not been substantially investigated. We quantified cytogenetic alterations of human cells, including primary lymphoid cells and non-tumorigenic and tumorigenic epithelial cell lines, exposed to PARPi at clinically relevant doses by both sister chromatid exchange (SCE) assays and chromosome spreading. As expected, both olaparib and veliparib effectively inhibited poly-ADP-ribosylation (PAR), and caused marked hypersensitivity in HR-deficient cells. Significant dose-dependent increases in SCEs were observed in normal and non-tumorigenic cells with minimal residual PAR activity. Clinically relevant doses of the FDA-approved olaparib led to a marked increase of SCEs (5-10-fold) and chromatid aberrations (2-6-fold). Furthermore, olaparib potentiated SCE induction by cisplatin in normal human cells. Our data have important implications for therapies with regard to sustained genotoxicity to normal cells. Genomic instability arising from PARPi warrants consideration, especially if these agents will be used in people with early stage cancers, in prevention strategies or for non-oncologic indications. PMID:27428646

  1. [Teflon granuloma after microvascular decompression of the trigeminal nerve root in a patient with recurrent trigeminal neuralgia].

    PubMed

    Rzaev, D A; Kulikova, E V; Moysak, G I; Voronina, E I; Ageeva, T A

    2016-01-01

    The use of a Teflon implant for Jannetta surgery in patients with trigeminal neuralgia is complicated in rare cases by the development of a Teflon granuloma and can cause recurrent facial pain. The article presents a clinical case of a Teflon granuloma developed after microvascular decompression of the trigeminal nerve root, describes the surgical findings and histological picture, and analyzes the literature, causes of granuloma development, and recommendations for treatment of these patients.

  2. Transcriptome analysis of the normal human mammary cell commitment and differentiation process.

    PubMed

    Raouf, Afshin; Zhao, Yun; To, Karen; Stingl, John; Delaney, Allen; Barbara, Mary; Iscove, Norman; Jones, Steven; McKinney, Steven; Emerman, Joanne; Aparicio, Samuel; Marra, Marco; Eaves, Connie

    2008-07-03

    Mature mammary epithelial cells are generated from undifferentiated precursors through a hierarchical process, but the molecular mechanisms involved, particularly in the human mammary gland, are poorly understood. To address this issue, we isolated highly purified subpopulations of primitive bipotent and committed luminal progenitor cells as well as mature luminal and myoepithelial cells from normal human mammary tissue and compared their transcriptomes obtained using three different methods. Elements unique to each subset of mammary cells were identified, and changes that accompany their differentiation in vivo were shown to be recapitulated in vitro. These include a stage-specific change in NOTCH pathway gene expression during the commitment of bipotent progenitors to the luminal lineage. Functional studies further showed NOTCH3 signaling to be critical for this differentiation event to occur in vitro. Taken together, these findings provide an initial foundation for future delineation of mechanisms that perturb primitive human mammary cell growth and differentiation.

  3. Expression and characterization of erythropoietin receptors on normal human bone marrow cells

    SciTech Connect

    Hoshino, S.; Teramura, M.; Takahashi, M.; Motoji, T.; Oshimi, K.; Ueda, M.; Mizoguchi, H.

    1989-05-01

    We studied the specific binding of /sup 125/I-labeled bioactive recombinant human erythropoietin (Epo) to human bone marrow mononuclear cells (BMNC) obtained from normal subjects. The /sup 125/I-labeled Epo bound specifically to the BMNC. Scatchard analysis of the data showed two classes of binding sites; one high affinity (Kd 0.07 nM) and the other low affinity (Kd 0.38 nM). The number of Epo binding sites per BMNC was 46 +/- 16 high-affinity receptors and 91 +/- 51 low-affinity receptors. The specific binding was displaced by unlabeled Epo, but not by other growth factors. Receptor internalization was observed significantly at 37 degrees C, but was prevented by the presence of 0.2% sodium azide. These findings indicate that human BMNC possess two classes of specific Epo receptors with characteristics of a hormone-receptor association.

  4. Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line

    PubMed Central

    1988-01-01

    In contrast to mouse epidermal cells, human skin keratinocytes are rather resistant to transformation in vitro. Immortalization has been achieved by SV40 but has resulted in cell lines with altered differentiation. We have established a spontaneously transformed human epithelial cell line from adult skin, which maintains full epidermal differentiation capacity. This HaCaT cell line is obviously immortal (greater than 140 passages), has a transformed phenotype in vitro (clonogenic on plastic and in agar) but remains nontumorigenic. Despite the altered and unlimited growth potential, HaCaT cells, similar to normal keratinocytes, reform an orderly structured and differentiated epidermal tissue when transplanted onto nude mice. Differentiation- specific keratins (Nos. 1 and 10) and other markers (involucrin and filaggrin) are expressed and regularly located. Thus, HaCaT is the first permanent epithelial cell line from adult human skin that exhibits normal differentiation and provides a promising tool for studying regulation of keratinization in human cells. On karyotyping this line is aneuploid (initially hypodiploid) with unique stable marker chromosomes indicating monoclonal origin. The identity of the HaCaT line with the tissue of origin was proven by DNA fingerprinting using hypervariable minisatellite probes. This is the first demonstration that the DNA fingerprint pattern is unaffected by long- term cultivation, transformation, and multiple chromosomal alterations, thereby offering a unique possibility for unequivocal identification of human cell lines. The characteristics of the HaCaT cell line clearly document that spontaneous transformation of human adult keratinocytes can occur in vitro and is associated with sequential chromosomal alterations, though not obligatorily linked to major defects in differentiation. PMID:2450098

  5. Calcium currents and transients in co-cultured contracting normal and Duchenne muscular dystrophy human myotubes

    PubMed Central

    Imbert, Nathalie; Vandebrouck, Clarisse; Duport, Gérard; Raymond, Guy; Hassoni, Abdul A; Constantin, Bruno; Cullen, Michael J; Cognard, Christian

    2001-01-01

    The goal of the present study was to investigate differences in calcium movements between normal and Duchenne muscular dystrophy (DMD) human contracting myotubes co-cultured with explants of rat spinal cord with attached dorsal root ganglia. Membrane potential, variations of intracellular calcium concentration and T- and L-type calcium currents were recorded. Further, a descriptive and quantitative study by electron microscopy of the ultrastructure of the co-cultures was carried out. The resting membrane potential was slightly less negative in DMD (−61.4 ± 1.1 mV) than in normal myotubes (−65.5 ± 0.9 mV). Both types of myotube displayed spontaneous action potentials (mean firing frequency, 0.42 and 0.16 Hz, respectively), which triggered spontaneous calcium transients measured with Indo-1. The time integral under the spontaneous Ca2+ transients was significantly greater in DMD myotubes (97 ± 8 nm s) than in normal myotubes (67 ± 13 nm s). The L- and T-type current densities estimated from patch-clamp recordings were smaller in DMD cells (2.0 ± 0.5 and 0.90 ± 0.19 pA pF−1, respectively) than in normal cells (3.9 ± 0.7 and 1.39 ± 0.30 pA pF−1, respectively). The voltage-dependent inactivation relationships revealed a shift in the conditioning potential at which inactivation is half-maximal (Vh,0.5) of the T- and L-type currents towards less negative potentials, from −72.1 ± 0.7 and −53.7 ± 1.5 mV in normal cells to −61.9 ± 1.4 and −29.2 ± 1.4 mV in DMD cells, respectively. Both descriptive and quantitative studies by electron microscopy suggested a more advanced development of DMD myotubes as compared to normal ones. This conclusion was supported by the significantly larger capacitance of the DMD myotubes (408 ± 45 pF) than of the normal myotubes (299 ± 34 pF) of the same apparent size. Taken together, these results show that differences in T- and L-type calcium currents between normal and DMD myotubes cannot simply explain all observed

  6. Analysis of differential protein expression in normal and neoplastic human breast epithelial cell lines

    SciTech Connect

    Williams, K.; Chubb, C.; Huberman, E.; Giometti, C.S.

    1997-07-01

    High resolution two dimensional get electrophoresis (2DE) and database analysis was used to establish protein expression patterns for cultured normal human mammary epithelial cells and thirteen breast cancer cell lines. The Human Breast Epithelial Cell database contains the 2DE protein patterns, including relative protein abundances, for each cell line, plus a composite pattern that contains all the common and specifically expressed proteins from all the cell lines. Significant differences in protein expression, both qualitative and quantitative, were observed not only between normal cells and tumor cells, but also among the tumor cell lines. Eight percent of the consistently detected proteins were found in significantly (P < 0.001) variable levels among the cell lines. Using a combination of immunostaining, comigration with purified protein, subcellular fractionation, and amino-terminal protein sequencing, we identified a subset of the differentially expressed proteins. These identified proteins include the cytoskeletal proteins actin, tubulin, vimentin, and cytokeratins. The cell lines can be classified into four distinct groups based on their intermediate filament protein profile. We also identified heat shock proteins; hsp27, hsp60, and hsp70 varied in abundance and in some cases in the relative phosphorylation levels among the cell lines. Finally, we identified IMP dehydrogenase in each of the cell lines, and found the levels of this enzyme in the tumor cell lines elevated 2- to 20-fold relative to the levels in normal cells.

  7. Classification of normal and malignant human gastric mucosa tissue with confocal Raman microspectroscopy and wavelet analysis

    NASA Astrophysics Data System (ADS)

    Hu, Yaogai; Shen, Aiguo; Jiang, Tao; Ai, Yong; Hu, Jiming

    2008-02-01

    Thirty-two samples from the human gastric mucosa tissue, including 13 normal and 19 malignant tissue samples were measured by confocal Raman microspectroscopy. The low signal-to-background ratio spectra from human gastric mucosa tissues were obtained by this technique without any sample preparation. Raman spectral interferences include a broad featureless sloping background due to fluorescence and noise. They mask most Raman spectral feature and lead to problems with precision and quantitation of the original spectral information. A preprocessed algorithm based on wavelet analysis was used to reduce noise and eliminate background/baseline of Raman spectra. Comparing preprocessed spectra of malignant gastric mucosa tissues with those of counterpart normal ones, there were obvious spectral changes, including intensity increase at ˜1156 cm -1 and intensity decrease at ˜1587 cm -1. The quantitative criterion based upon the intensity ratio of the ˜1156 and ˜1587 cm -1 was extracted for classification of the normal and malignant gastric mucosa tissue samples. This could result in a new diagnostic method, which would assist the early diagnosis of gastric cancer.

  8. Dielectric spectroscopy of normal and malignant human lung cells at ultra-high frequencies.

    PubMed

    Egot-Lemaire, S; Pijanka, J; Sulé-Suso, J; Semenov, S

    2009-04-21

    Microwave techniques for biomedical applications aimed at cancer treatment or diagnosis, either by imaging or spectroscopy, are promising. Their use relies on knowledge of the dielectric properties of tissues, especially on a detectable difference between malignant and normal tissues. As most studies investigated the dielectric properties of ex vivo tissues, there is a need for better biophysical understanding of human tissues in their living state. As an essential component of tissues, cells represent valuable objects of analysis. The approach developed in this study is an investigation at cell level. Its aim was to compare human lung normal and malignant cells by dielectric spectroscopy in the beginning of the microwave range, where such information is of substantial biomedical importance. These cells were embedded in small and low-conductivity agarose hydrogels and laid on an open-ended coaxial probe connected to a vector network analyser operated from 200 MHz to 2 GHz. The comparison between normal and malignant cells was drawn using the variation of measured dielectric properties and fitting the measurements using the Maxwell-Wagner equation. Both methods revealed slight differences between the two cell lines, which were statistically significant regarding conductivities of composite gels and cells.

  9. Normal genetic variation of the human foot: part 1: the paradox of normal anatomical alignment in an evolutionary epigenetic context.

    PubMed

    Quinn, Greg

    2012-01-01

    Molecular genetics is changing our understanding of the developmental translation of genotype to phenotype between and within different phylogenetic groups. Together with a growing understanding of our own evolutionary relationships to common ancestors, the epigenetic processes involved enforce a reexamination of what is regarded as a normal foot structure. A revised populationist approach is proposed and supported by paleoanthropologic evidence that reflects a picture of emerging suitability for bipedalism that is driven by natural genetic divergence.

  10. Modulation of ABH histo-blood group antigen expression in normal and myasthenic human thymus.

    PubMed

    Sarafian, Victoria S; Marinova, Tsvetana T

    2006-10-01

    The role of ABH histo-blood group antigens (HBGA) in intercellular communication during normal and pathological processes is still uncertain. The present work investigates the expression of ABH HBGA in epithelial cells and lymphocytes in normal thymus, and characterizes the modulation of their immunoreactivity during myasthenic transformation. Immunohistochemistry and immunoelectron microscopy were applied on normal young thymus and on myasthenia gravis-associated thymomas and thymic hyperplasias. The Hassall's corpuscules in the thymus of young individuals were homogeneously stained for HBGA, while in hyperplastic glands only their central part was positive. Stromal epithelial cells permanently expressed HBGA in all tissue samples. In thymomas, mainly the lymphocytes in close proximity to antigen expressing epithelial cells were positive, while in the hyperplastic gland the most intensely stained lymphocytes were those within Hassall's corpuscules. Novel evidence for modulation of ABH antigen reactivity in normal and myasthenic human thymus is presented. It suggests that HBGA might participate in the regulation of the cross-talk in the thymocyte microenvironment throughout the ontogeny, as well as during the myasthenic transformation.

  11. Expression of metalloprotease insulin-degrading enzyme (insulysin) in normal and malignant human tissues

    PubMed Central

    Yfanti, Christina; Mengele, Karin; Gkazepis, Apostolos; Weirich, Gregor; Giersig, Cecylia; Kuo, Wen-Liang; Tang, Wei-Jen; Rosner, Marsha; Schmitt, Manfred

    2013-01-01

    Background Insulin-degrading enzyme (IDE, insulysin, insulinase; EC 3.4.22.11), a thiol metalloendopeptidase, is involved in intracellular degradation of insulin, thereby inhibiting its translocation and accumulation to the nucleus. Recently, protein expression of IDE has been demonstrated in the epithelial ducts of normal breast and in breast cancer tissue (Radulescu et al., Int J Oncol 30:73; 2007). Materials and Methods Utilizing four different antibodies generated against different epitopes of the IDE molecule, we performed western blot analysis and immunohistochemical staining on several normal human tissues, on a plethora of tumor cell lines of different tissue origin, and on malignant breast and ovarian tissue. Results Applying the four IDE-directed antibodies, we demonstrate IDE expression at the protein level, both by means of immunoblotting and immunocytochemistry, in all of the tumor cell lines analyzed. Besides, IDE protein expression was found in normal tissues of the kidney, liver, lung, brain, breast and skeletal muscle, as well as in breast and ovarian cancer tissues. Immunohistochemical visualization of IDE indicated cytoplasmic localization of IDE in all of the cell lines and tissues assessed. Conclusions We performed for the first time a wide-ranging survey on IDE protein expression in normal and malignant tissues and cells and thus extend knowledge about cellular and tissue distribution of IDE, an enzyme which so far has mainly been studied in connection with Alzheimer’s disease and diabetes but not in cancer. PMID:18813847

  12. Human embryonic stem cells passaged using enzymatic methods retain a normal karyotype and express CD30.

    PubMed

    Thomson, Alison; Wojtacha, Davina; Hewitt, Zoë; Priddle, Helen; Sottile, Virginie; Di Domenico, Alex; Fletcher, Judy; Waterfall, Martin; Corrales, Néstor López; Ansell, Ray; McWhir, Jim

    2008-03-01

    Human embryonic stem cells (hESCs) are thought to be susceptible to chromosomal rearrangements as a consequence of single cell dissociation. Compared in this study are two methods of dissociation that do not generate single cell suspensions (collagenase and EDTA) with an enzymatic procedure using trypsin combined with the calcium-specific chelator EGTA (TEG), that does generate a single cell suspension, over 10 passages. Cells passaged by single cell dissociation using TEG retained a normal karyotype. However, cells passaged using EDTA, without trypsin, acquired an isochromosome p7 in three replicates of one experiment. In all of the TEG, collagenase and EDTA-treated cultures, cells retained consistent telomere length and potentiality, demonstrating that single cell dissociation can be used to maintain karyotypically and phenotypically normal hESCs. However, competitive genomic hybridization revealed that subkaryotypic deletions and amplifications could accumulate over time, reinforcing that present culture regimes remain suboptimal. In all cultures the cell surface marker CD30, reportedly expressed on embryonal carcinoma but not karyoptically normal ESCs, was expressed on hESCs with both normal and abnormal karyotype, but was upregulated on the latter.

  13. Defining the restriction point in normal asynchronous human peripheral blood lymphocytes.

    PubMed

    Jiang, Jianwu; Liu, Liang; Li, Xiaolan; Tao, Deding; Hu, Junbo; Qin, Jichao

    2013-10-01

    Although the restriction point (R-point) was proposed in animal cells several decades ago, its existence in normal cells is still controversial, because, in most studies, long-term cultured cell lines rather than primary normal cells were used. Furthermore, cell synchronization was generally applied, resulting in growth imbalance between DNA synthesis and protein expression in cells. Finally, R-point was originally proposed as a unique arrest point that may be in G0 phase; however, generally believed R-point locates within G1 phase. Thus, up to now, there is no solid experimental evidence that supports the existence of R-point in asynchronous primary normal cells. In this study, we used freshly purified peripheral human blood lymphocytes, as asynchronous primary normal cells, to confirm the existence of restriction point in G1 not G0 phase. Our findings may help uncover the mystery of the deregulation of cell cycle progression in malignant tumors. © 2013 International Society for Advancement of Cytometry.

  14. Immunosuppressive activity of human amniotic fluid of normal and abnormal pregnancies.

    PubMed

    Shohat, B; Faktor, J M

    1988-01-01

    Twenty specimens of amniotic fluid (AF) obtained between week 16 and 18 of gestation from normal pregnant women and six specimens from pregnant women in which trisomia of chromosome 21 was found were tested for immunosuppressive activity. Incubation of normal human donor lymphocytes with 0.2-1 mL of AF from normal pregnant women for one hour at 37 degrees C was sufficient for induction of significant inhibition of the ability of these cells to induce a local xenogeneic graft-versus-host reaction (GVHR) as well as inhibition of E and E-active rosette formation, the GVHR being the most sensitive test. On the other hand, amniotic fluid obtained from the six pregnant women in which trisomia of chromosome 21 was found showed no inhibitory activity in either the E or E-active rosette formation, nor in the local xenogeneic graft-versus-host reaction. AF from all the women tested was found to have no effect on phenotype expression of the lymphocytes, as tested by the monoclonal antibodies OKT4+ and OKT8+, nor on B-lymphocytes, as tested by surface immunoglobulins. No correlation was found between the alpha-fetoprotein levels in the sera of those women and the immunosuppressive activity. These findings indicate that genetic defects of the conceptus are not limited to the embryo but may affect the composition of immunosuppressive components present in normal amniotic fluid.

  15. Surface modification of microparticles causes differential uptake responses in normal and tumoral human breast epithelial cells

    NASA Astrophysics Data System (ADS)

    Patiño, Tania; Soriano, Jorge; Barrios, Lleonard; Ibáñez, Elena; Nogués, Carme

    2015-06-01

    The use of micro- and nanodevices as multifunctional systems for biomedical applications has experienced an exponential growth during the past decades. Although a large number of studies have focused on the design and fabrication of new micro- and nanosystems capable of developing multiple functions, a deeper understanding of their interaction with cells is required. In the present study, we evaluated the effect of different microparticle surfaces on their interaction with normal and tumoral human breast epithelial cell lines. For this, AlexaFluor488 IgG functionalized polystyrene microparticles (3 μm) were coated with Polyethyleneimine (PEI) at two different molecular weights, 25 and 750 kDa. The effect of microparticle surface properties on cytotoxicity, cellular uptake and endocytic pathways were assessed for both normal and tumoral cell lines. Results showed a differential response between the two cell lines regarding uptake efficiency and mechanisms of endocytosis, highlighting the potential role of microparticle surface tunning for specific cell targeting.

  16. Transforming growth factor alpha and epidermal growth factor levels in normal human gastrointestinal mucosa.

    PubMed Central

    Cartlidge, S. A.; Elder, J. B.

    1989-01-01

    Acid soluble proteins from 23 samples of normal human gastrointestinal mucosa derived from four normal adult organ donors were extracted and subjected to specific radiommunoassays for transforming growth factor alpha (TGF alpha) and urogastrone epidermal growth factor (URO-EGF). All tissues were found to contain immunoreactive TGF alpha and levels ranged from 57 to 4,776 pg-1 wet weight of tissue. Although levels varied between tissue donors, the distribution of TGF alpha throughout the gastrointestinal tract appeared similar in all cases. URO-EGF levels were much lower (0-216 pg g-1 wet weight). TGF alpha levels in extracts of gastrointestinal mucosa from a 7-year-old female donor were higher and the observed distribution was markedly different from adult levels. URO-EGF was not detected in mucosal or submucosal tissue extracts from this patient. Further studies in juveniles are indicated. PMID:2803941

  17. Phosphatidic acid phosphatase activity in subcellular fractions of normal and dystrophic human muscle.

    PubMed

    Kunze, D; Rüstow, B; Olthoff, D; Jung, K

    1985-03-15

    Biopsy samples from normal and dystrophic human muscle (Duchenne type) were fractionated by differential centrifugation and microsomes, mitochondria and cytosol were assayed for phosphatidic acid phosphatase (EC 3.1.3.4) and marker enzymes of mitochondria and cytosol. The activity of phosphatidic acid phosphatase was significantly lower in microsomes and higher in cytosol and mitochondria of dystrophic muscle than in the corresponding subcellular fractions of normal muscle. The results support an explanation of earlier findings that there is reduced G3P incorporation into diglycerides and phosphatidylcholine and a qualitative and quantitative change in the amount of phosphatidylcholine in dystrophic microsomes. The possible reasons for the reduction in the activity of only microsomal PA-P-ase were discussed.

  18. Effects of penicillinase on bactericidal and complement activities in normal human serum.

    PubMed Central

    Biggs, W H; Wunderlich, A C; Corbeil, L C; Davis, C E; Curd, J G

    1983-01-01

    During routine addition of penicillinase (beta-lactamase) to patients sera, we found that the capacity of some of these sera to kill serum-sensitive gram-negative organisms was significantly decreased. Further controlled studies showed that penicillinase decreased both the bactericidal activity of normal human sera and the total hemolytic activity (CH50) of complement in these sera. The decreased bactericidal activity correlated significantly (r = 0.57, P less than 0.05) with the reduction of CH50 in eight normal sera. These effects of penicillinase were time and temperature dependent. Measurement of individual complement component activities showed that penicillinase decreased the activity of C2, C4, and C3-C9, suggesting that the penicillinase preparation activated the classical pathway. These results cast doubts on the validity of bactericidal determinations when sera are pretreated with penicillinase. PMID:6603195

  19. Characterization of two different agglutinators in the latex fixation test, occurring in normal human sera

    PubMed Central

    Klein, F.; Valkenburg, H. A.; Van Zwet, Theda L.; Lafeber, Geertruida J. M.

    1966-01-01

    Using a sensitive modification of the latex fixation test it is possible to detect a small agglutinating effect in about 60 per cent of normal human sera, after these have been heated for 30 minutes at 56°. This was shown to be caused by an IgM globulin with the properties of a rheumatoid factor. The factor is able to react with human IgG globulin and may represent an antibody to the IgG part of circulating antigen—antibody complexes. The heat treatment probably inactivates an inhibitor of the latex fixation reaction. In addition all normal human sera give an agglutination reaction with IgG coated latex at incubation temperatures of 37° or lower. It was shown that these reactions are caused by a thermolabile, non-reducible component with a sedimentation constant of about 10. This component is probably identical with the complement component C'1q. The agglutinating activity was found in the α2—β1 region after electrophoresis of untreated serum, but in the slow γ region after treatment of the serum with EDTA. This kind of agglutination may cause false positive reactions in latex tests which are carried out at 37° or less. ImagesFIG. 1FIG. 3 PMID:4160336

  20. Percutaneous trigeminal ganglion radiofrequency thermocoagulation alleviates anxiety and depression disorders in patients with classic trigeminal neuralgia

    PubMed Central

    Tang, YuanZhang; Ma, Ling; Li, Na; Guo, Yuna; Yang, Liqiang; Wu, Baishan; Yue, Jianning; Wang, Qi; Liu, Jingjie; Ni, Jia-xiang

    2016-01-01

    Abstract Trigeminal neuralgia (TN) is a neurological condition that presents as excruciating facial pain. Depression and anxiety are commonly associated with TN; however, anxiety and depression disorders in patients with TN and the effects of the various therapeutic strategies for TN on these disorders are not well studied. To evaluate depression and anxiety in patients with trigeminal neuralgia (TN), identify factors that predict their occurrence and study the effect of the percutaneous trigeminal ganglion radiofrequency thermocoagulation (PRT) procedure for alleviating pain on depression and anxiety. Patients with classic TN, who received PRT treatment, were consecutively recruited between October 2014 and October 2015. Severity of pain was determined using the visual analogue scale (VAS) score. Beck Depression Inventory-II (BDI) and Beck anxiety Inventory (BAI) were used to evaluate depression and anxiety disorders pre- and post-PRT. Medical, demographic, and psychosocial backgrounds were also assessed as predictive factors. A BDI score of ≥14 represented depression and BAI score of ≥45 represented anxiety. VAS, BDI, and BAI scores were collected at the time of admission and on the day of discharge. Of the 167 patients who participated in the study, 121 (72.5%) had depression and 34 (20.4%) suffered anxiety. Pre-PRT procedure, female sex, age >50 years, ineffective treatment, and high pain intensity (VAS ≥7) predicted the development of depression and anxiety. Post-PRT procedure, all patients who experienced pain relief also reported amelioration of depression and anxiety. A considerable percentage of patients with TN developed depression and anxiety. Patients who were female, older than 50 years, or suffered from failure treatment and severe pain (VAS>7), were at higher risk of depression and anxiety development. Complete alleviation of pain by using surgical PRT could immediately attenuate depressive and anxiety disorders associated with TN. PMID

  1. Dosimetric analysis of trigeminal nerve, brain stem doses in CyberKnife radiosurgery of trigeminal neuralgia.

    PubMed

    Sudahar, H; Kurup, P G G; Murali, V; Velmurugan, J

    2012-07-01

    CyberKnife radiosurgery treatment of Trigeminal neuralgia (TN) is performed as a non-invasive image guided procedure. The prescription dose for TN is very high. The brainstem is the adjacent critical organ at risk (OAR) which is prone to receive the very high target dose of TN. The present study is to analyze the dose distribution inside the tiny trigeminal nerve target and also to analyze the dose fall off in the brain stem. Seven TN cases treated between November 2010 and January 2012 were taken for this study retrospectively. The treatment plans were analyzed for target dose conformity, homogeneity and dose coverage. In the brainstem the volume doses D(1%), D(2%) were taken for analyzing the higher doses in the brain stem. The dose fall off was analyzed in terms of D(5%) and D(10%). The mean value of maximum dose within the trigeminal nerve target was 73.5±2.1Gy (P=0.0007) and the minimum dose was 50.0±4.1Gy (P=0.1315). The mean conformity index was 2.19 and the probable reason could be the smallest CyberKnife collimator of 5mm used in the treatment plan. The mean D(1%), of the brainstem was 10.5± 2.1Gy (P=0.5316) and the mean value of the maximum point dose within the brainstem was 35.6±3.8Gy. This shows the degree of dose fall off within the brainstem. Though the results of the present study are showing superior sparing of brain stem and reasonable of target coverage, it is necessary to execute the treatment plan with greater accuracy in CyberKnife as the immobilization is noninvasive and frameless.

  2. Normal human epithelial cells regulate the size and morphology of tissue-engineered capillaries.

    PubMed

    Rochon, Marie-Hélène; Fradette, Julie; Fortin, Véronique; Tomasetig, Florence; Roberge, Charles J; Baker, Kathleen; Berthod, François; Auger, François A; Germain, Lucie

    2010-05-01

    The survival of thick tissues/organs produced by tissue engineering requires rapid revascularization after grafting. Although capillary-like structures have been reconstituted in some engineered tissues, little is known about the interaction between normal epithelial cells and endothelial cells involved in the in vitro angiogenic process. In the present study, we used the self-assembly approach of tissue engineering to examine this relationship. An endothelialized tissue-engineered dermal substitute was produced by adding endothelial cells to the tissue-engineered dermal substitute produced by the self-assembly approach. The latter consists in culturing fibroblasts in the medium supplemented with serum and ascorbic acid. A network of tissue-engineered capillaries (TECs) formed within the human extracellular matrix produced by dermal fibroblasts. To determine whether epithelial cells modify TECs, the size and form of TECs were studied in the endothelialized tissue-engineered dermal substitute cultured in the presence or absence of epithelial cells. In the presence of normal keratinocytes from skin, cornea or uterine cervix, endothelial cells formed small TECs (cross-sectional area estimated at less than 50 microm(2)) reminiscent of capillaries found in the skin's microcirculation. In contrast, TECs grown in the absence of epithelial cells presented variable sizes (larger than 50 microm(2)), but the addition of keratinocyte-conditioned media or exogenous vascular endothelial growth factor induced their normalization toward a smaller size. Vascular endothelial growth factor neutralization inhibited the effect of keratinocyte-conditioned media. These results provide new direct evidence that normal human epithelial cells play a role in the regulation of the underlying TEC network, and advance our knowledge in tissue engineering for the production of TEC networks in vitro.

  3. Differentiation between normal and tumor vasculature of animal and human glioma by FTIR imaging.

    PubMed

    Wehbe, Katia; Pineau, Raphael; Eimer, Sandrine; Vital, Anne; Loiseau, Hugues; Déléris, Gérard

    2010-12-01

    Malignant gliomas are very aggressive tumors, highly angiogenic and invading heterogeneously the surrounding brain parenchyma, making their resection very difficult. To overcome the limits of current diagnostic imaging techniques used for gliomas, we proposed using FTIR imaging, with a spatial resolution from 6 to 10 μm, to provide molecular information for their histological examination, based on discrimination between normal and tumor vasculature. Differentiation between normal and tumor blood vessel spectra by hierarchical cluster analysis was performed on tissue sections obtained from xenografted brain tumors of Rag-gamma mice 28 days after intracranial implantation of glioma cells, as well as for human brain tumors obtained in clinics. Classical pathological examination and immunohistochemistry were performed in parallel to the FTIR spectral imaging of brain tissues. First on the animal model, classification of FTIR spectra of blood vessels could be performed using spectral intervals based on fatty acyl (3050-2800 cm(-1)) and carbohydrate (1180-950 cm(-1)) absorptions, with the formation of two clusters corresponding to healthy and tumor parts of the tissue sections. Further data treatments on these two spectral intervals provided interpretable information about the molecular contents involved in the differentiation between normal and tumor blood vessels, the latter presenting a higher level of fatty acyl chain unsaturation and an unexpected loss of absorption from osidic residues. This classification method was further successfully tested on human glioma tissue sections. These findings demonstrate that FTIR imaging could highlight discriminant molecular markers to distinguish between normal and tumor vasculature, and help to delimitate areas of corresponding tissue.

  4. Quantifying normal geometric variation in human pulmonary lobar geometry from high resolution computed tomography.

    PubMed

    Chan, Ho-Fung; Clark, Alys R; Hoffman, Eric A; Malcolm, Duane T K; Tawhai, Merryn H

    2015-05-01

    Previous studies of the ex vivo lung have suggested significant intersubject variability in lung lobe geometry. A quantitative description of normal lung lobe shape would therefore have value in improving the discrimination between normal population variability in shape and pathology. To quantify normal human lobe shape variability, a principal component analysis (PCA) was performed on high resolution computed tomography (HRCT) imaging of the lung at full inspiration. Volumetric imaging from 22 never-smoking subjects (10 female and 12 male) with normal lung function was included in the analysis. For each subject, an initial finite element mesh geometry was generated from a group of manually selected nodes that were placed at distinct anatomical locations on the lung surface. Each mesh used cubic shape functions to describe the surface curvilinearity, and the mesh was fitted to surface data for each lobe. A PCA was performed on the surface meshes for each lobe. Nine principal components (PCs) were sufficient to capture >90% of the normal variation in each of the five lobes. The analysis shows that lobe size can explain between 20% and 50% of intersubject variability, depending on the lobe considered. Diaphragm shape was the next most significant intersubject difference. When the influence of lung size difference is removed, the angle of the fissures becomes the most significant shape difference, and the variability in relative lobe size becomes important. We also show how a lobe from an independent subject can be projected onto the study population's PCs, demonstrating potential for abnormalities in lobar geometry to be defined in a quantitative manner.

  5. The significance of paired astrocyte nuclei in normal human nervous tissue.

    PubMed Central

    Pittella, J E; Brasileiro-Filho, G

    1987-01-01

    A quantitative study of astrocytes was carried out in 80 microscopic fields and the number of paired nuclei in 100 consecutive astrocytes of the temporo-occipital gyrus cortex was determined in 13 patients with no cerebral or liver disease. No significant correlation was found between astrocyte number and the percentage of paired nuclei. When studies on astrocytes in hepatic encephalopathy, liver cirrhosis and hepatosplenic schistosomiasis are taken into consideration it is suggested that these cells are in continuous variable renewal in normal adult human nervous tissue, as occurs in other animal species. Images Fig. 1 PMID:3654344

  6. Nystagmus responses in a group of normal humans during earth-horizontal axis rotation

    NASA Technical Reports Server (NTRS)

    Wall, Conrad, III; Furman, Joseph M. R.

    1989-01-01

    Horizontal eye movement responses to earth-horizontal yaw axis rotation were evaluated in 50 normal human subjects who were uniformly distributed in age (20-69 years) and each age group was then divided by gender. Subjects were rotated with eyes open in the dark, using clockwise and counter-clockwise 60 deg velocity trapezoids. The nystagmus slow component velocity is analyzed. It is shown that, despite large intersubject variability, parameters which describe earth-horizontal yaw axis responses are loosely interrelated, and some of them vary significantly with gender and age.

  7. Expression of splice variants of mts1 gene in normal and neoplastic human tissues

    SciTech Connect

    Ambartsumyan, N.S. |; Grigorian, M.S.; Lukanidin, E.M.

    1995-09-01

    Data on cloning of cDNA corresponding to human mts1 gene transcripts are presented. By comparing nucleotide sequences of the genomic DNA clone and cDNA of mts1, it was shown that human osteosarcoma OHS cells contain two alternative splice variants of mts1 transcripts. Alternative splicing occurs in the 5{prime}-untranslated region of the mts1 pre-mRNA. Both splice variants, hu-mts1 and hu-mts1(var), demonstrate similar stability in the cells, and each contains one open reading frame for the MTS1 protein. However, the two types of transcripts are translated with different effectiveness. The level of transcription of mts1 splice variants in different normal and neoplastic tissues and cell lines varies significantly. The role of alternative splicing as the mechanism responsible for posttranscriptional regulation of mts1 gene expression is discussed. 31 refs., 5 figs.

  8. Expression, localisation and functional activation of NFAT-2 in normal human skin, psoriasis, and cultured keratocytes

    PubMed Central

    Al-Daraji, Wael I; Malak, Tamer T.; Prescott, Richard J.; Abdellaoui, Adel; Ali, Mahmud M.; Dabash, Tarek; Zelger, Bettina G.; Zelger, Bernhard

    2009-01-01

    Ciclosporin A (CsA) is widely utilized for the treatment of inflammatory skin diseases such as psoriasis. The therapeutic effects of CsA are thought to be mediated via its immunosuppressive action on infiltrating lymphocytes in skin lesions. CsA and tacrolimus block T cell activation by inhibiting the phosphatase calcineurin and preventing translocation from the cytoplasm to the nucleus of the transcription factor Nuclear Factor of Activated T cells (NFAT). As calcineurin and NFAT 1 have been shown to be functionally active in cultured human keratocytes, expression of other NFAT family members such as NFAT-2 and possible functional activation was investigated in human keratocytes. RT-PCR and Western Analysis were used to investigate the presence of NFAT-2 mRNA and protein in human keratocytes. Tissue culture of human keratocytes and immunostaining of cells on coverslips and confocal microscopy were used to assess the degree of nuclear localisation of NFAT-2 in cultured cells. Keratome biopsies were taken from patients with psoriasis (lesional and non-lesional skin) and normal skin and immunohistochemistry was used to assess the NFAT-2 localisation in these biopsies using a well characterized anti-NFAT-2 antibody. The NFAT-2 mRNA and protein expression was demonstrated using RT-PCR and Western blotting. Moreover, the expression of NFAT-2 in normal skin, non-lesional and lesional psoriasis showed a striking basal staining suggesting a role for NFAT-2 in keratocytes proliferation. A range of cell types in the skin express NFAT-2. The expression of NFAT-2 in human keratocytes and response to different agonists provides perhaps a unique opportunity to examine the regulation, subcellular localization and kinetics of translocation of different NFATs in primary cultured human cells. In these experiments the author assessed the expression, localization of NFAT-2 in cultured human keratocytes and measured the degree of nuclear localisaion of NFAT-2 using immunofluorescence

  9. Lipid-mediated transfection of normal adult human hepatocytes in primary culture.

    PubMed

    Ourlin, J C; Vilarem, M J; Daujat, M; Harricane, M C; Domergue, J; Joyeux, H; Baulieux, J; Maurel, P

    1997-04-05

    The aim of this work was to develop a procedure for the lipid-mediated transfection of DNA into normal adult human hepatocytes in culture. Cells were plated in a serum-free culture medium at various cell densities, on plastic or collagen-coated dishes, both in the absence and in the presence of epidermal growth factor (EGF). The cells were incubated for various periods of time with mixtures of DNA-lipofectin or DNA-3 beta[N-(N',N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-chol) liposomes, and the efficiency of transfection was assessed by measuring the activity of reporter genes, beta-galactosidase or chloramphenicol acetyl-transferase (CAT). For comparison, similar experiments were carried out with human cell lines including HepG2, Caco-2, and WRL68. The efficiency of transfection (in percentage of cells) was not significantly different after transfection with lipofectin or DC-chol and comprised between 0.04 and 1.7% (extreme values) for different cultures. The efficiency of transfection decreased as the age or density of the culture increased and increased in cultures treated with EGF. Direct measurement of the rate of DNA synthesis suggested that the efficiency of transfection was related to the number of cells entering the S phase. Under the same conditions, the efficiency of transfection was one to two orders of magnitude greater in the three cell lines. A plasmid harboring 660 bp of the 5'-flanking region of CYP1A1 (containing two xenobiotic enhancer elements) fused upstream of the promoter of thymidine kinase and the CAT reporter gene was constructed. When this plasmid was transfected in human hepatocytes, CAT activity was induced as expected. We conclude that normal adult human hepatocytes can be transfected with exogenous DNA and that the transfected construct is regulated in the manner expected from in vivo studies.

  10. The effects of pravastatin on the normal human placenta: Lessons from ex-vivo models

    PubMed Central

    Swissa, Shani S.; Feinshtein, Valeria; Huleihel, Mahmoud; Holcberg, Gershon; Dukler, Doron

    2017-01-01

    Introduction Research in animal models and preliminary clinical studies in humans support the use of pravastatin for the prevention of preeclampsia. However, its use during pregnancy is still controversial due to limited data about its effect on the human placenta and fetus. Methods In the present study, human placental cotyledons were perfused in the absence or presence of pravastatin in the maternal reservoir (PraM). In addition, placental explants were treated with pravastatin for 5, 24 and 72 h under normoxia and hypoxia. We monitored the secretion of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), endothelial nitric oxide synthase (eNOS) expression and activation and the fetal vasoconstriction response to angiotensin-II. Results The concentrations of PlGF, sFlt-1 and sEng were not significantly altered by pravastatin in PraM cotyledons and in placental explants compared to control. Under hypoxic conditions, pravastatin decreased sFlt-1 concentrations. eNOS expression was significantly increased in PraM cotyledons but not in pravastatin-treated placental explants cultured under normoxia or hypoxia. eNOS phosphorylation was not significantly affected by pravastatin. The feto-placental vascular tone and the fetal vasoconstriction response to angiotensin-II, did not change following exposure of the maternal circulation to pravastatin. Conclusion We found that pravastatin does not alter the essential physiological functions of the placenta investigated in the study. The relevance of the study lays in the fact that it expands the current knowledge obtained thus far regarding the effect of the drug on the normal human placenta. This data is reassuring and important for clinicians that consider the treatment of high-risk patients with pravastatin, a treatment that exposes some normal pregnancies to the drug. PMID:28199380

  11. An alternatively spliced surfactant protein B mRNA in normal human lung: disease implication.

    PubMed Central

    Lin, Z; Wang, G; Demello, D E; Floros, J

    1999-01-01

    We identified an alternatively-spliced surfactant protein B (SP-B) mRNA from normal human lung with a 12 nt deletion at the beginning of exon 8. This deletion causes a loss of four amino acids in the SP-B precursor protein. Sequence comparison of the 3' splice sites reveals only one difference in the frequency of U/C in the 11 predominantly-pyrimidine nucleotide tract, 73% for the normal and 45% for the alternatively-spliced SP-B mRNA (77-99% for the consensus sequence). Analysis of SP-B mRNA in lung indicates that the abundance of the alternatively-spliced form is very low and varies among individuals. Although the relative abundance of the deletion form of SP-B mRNA remains constant among normal lungs, it is found with relatively higher abundance in the lungs of some individuals with diseases such as congenital alveolar proteinosis, respiratory distress syndrome, bronchopulmonary dysplasia, alveolar capillary dysplasia and hypophosphatasia. This observation points to the possibility that the alternative splicing is a potential regulatory mechanism of SP-B and may play a role in the pathogenesis of disease under certain circumstances. PMID:10493923

  12. Spectral and temporal near-infrared imaging of ex vivo cancerous and normal human breast tissues.

    PubMed

    Alrubaiee, M; Gayen, S K; Alfano, R R; Koutcher, J A

    2005-10-01

    Cancerous and normal ex vivo human breast tissues were investigated using spectroscopic and time-sliced two-dimensional (2-D) transillumination imaging methods in order to demonstrate the importance and potential of spectral and temporal measurements in breast cancer detection and diagnosis. The experimental arrangement for time-sliced optical imaging used 120 fs, 1 kHz repetition-rate, 800 nm light pulses from a Ti:sapphire laser system for sample illumination, and a 80 ps resolution ultrafast gated intensified camera system for recording 2-D time-sliced images. The spectroscopic imaging arrangement used 1225-1300 nm tunable output of a Cr: forsterite laser for sample illumination, a Fourier space gate to discriminate against multiple-scattered light, and a near-infrared area camera to record 2-D images. Images recorded with earlier temporal slices of transmitted light highlighted tumors, while those recorded with later slices accentuated normal tissues. When light was tuned closer to the 1203 nm absorption resonance of adipose tissues, a marked enhancement in contrast between the images of adipose and fibrous tissues was observed. A similar wavelength-dependent difference between normal and cancerous tissues was observed. These results correlate well with pathology and nuclear magnetic resonance based analyses of the samples.

  13. The Effect of Phototherapy on Cancer Predisposition Genes of Diabetic and Normal Human Skin Fibroblasts

    PubMed Central

    Tangtrakulwanich, Boonsin; Sangkhathat, Surasak

    2017-01-01

    The purpose of this study was to investigate whether LED light at different wavelengths affects the expression profile of 143 cancer predisposition genes in both diabetic and normal human fibroblasts. In this study, both diabetic and normal fibroblast cell lines were cultured and irradiated with red (635 nm), green (520 nm), and blue (465 nm) LED light for 10 minutes at 0.67 J/cm2 each. After that, mRNA from all cell lines was extracted for microarray analysis. We found that green light activates EPHB2, KIT, ANTXR2, ESCO2, MSR1, EXT1, TSC1, KIT, NF1, BUB1B, FANCD2, EPCAM, FANCD2, NF, DIS3L2, and RET in normal fibroblast cells, while blue and red light can upregulate RUNX1, PDGFRA, EHBP1, GPC3, AXIN2, KDR, GLMN, MSMB, EPHB2, MSR1, KIT, FANCD2, BMPR1A, BUB1B, PDE11A, and RET. Therefore, genetic screening before phototherapy treatment may be required. PMID:28386563

  14. Pain in trigeminal neuralgia: neurophysiology and measurement: a comprehensive review.

    PubMed

    Kumar, S; Rastogi, S; Kumar, S; Mahendra, P; Bansal, M; Chandra, L

    2013-01-01

    Trigeminal neuralgia (TN) is defined as sudden, usually unilateral, severe, brief, stabbing recurrent episodes of pain within the distribution of one or more branches of the trigeminal nerve. It is the most frequent cranial neuralgia, the incidence being 1 per 1,000,00 persons per year. Pain attacks start abruptly and last several seconds but may persist 1 to 2 minutes. The attacks are initiated by non painful physical stimulation of specific areas (trigger points or zones) that are located ipsilateral to the pain. After each episode, there is usually a refractive period during which stimulation of the trigger zone will not induce the pain. According to the European Federation of Neurological Societies (EFNS) guidelines on neuropathic pain assessment and the American Academy of Neurology (AAN)-EFNS guidelines on TN management the neurophysiological recording of trigeminal reflexes represents the most useful and reliable test for the neurophysiological diagnosis of trigeminal pains. The present article discusses different techniques for investigation of the trigeminal system by which an accurate topographical diagnosis and profile of sensory fiber pathology can be determined. With the aid of neurophysiological recordings and quantitative sensory testing, it is possible to approach a mechanism-based classification of orofacial pain.

  15. Pain in trigeminal neuralgia: neurophysiology and measurement: a comprehensive review

    PubMed Central

    Kumar, S; Rastogi, S; Kumar, S; Mahendra, P; Bansal, M; Chandra, L

    2013-01-01

    Abstract Trigeminal neuralgia (TN) is defined as sudden, usually unilateral, severe, brief, stabbing recurrent episodes of pain within the distribution of one or more branches of the trigeminal nerve. It is the most frequent cranial neuralgia, the incidence being 1 per 1,000,00 persons per year. Pain attacks start abruptly and last several seconds but may persist 1 to 2 minutes. The attacks are initiated by non painful physical stimulation of specific areas (trigger points or zones) that are located ipsilateral to the pain. After each episode, there is usually a refractive period during which stimulation of the trigger zone will not induce the pain. According to the European Federation of Neurological Societies (EFNS) guidelines on neuropathic pain assessment and the American Academy of Neurology (AAN)-EFNS guidelines on TN management the neurophysiological recording of trigeminal reflexes represents the most useful and reliable test for the neurophysiological diagnosis of trigeminal pains. The present article discusses different techniques for investigation of the trigeminal system by which an accurate topographical diagnosis and profile of sensory fiber pathology can be determined. With the aid of neurophysiological recordings and quantitative sensory testing, it is possible to approach a mechanism-based classification of orofacial pain. PMID:24701256

  16. Classification issues related to neuropathic trigeminal pain.

    PubMed

    Zakrzewska, Joanna M

    2004-01-01

    The goal of a classification system of medical conditions is to facilitate accurate communication, to ensure that each condition is described uniformly and universally and that all data banks for the storage and retrieval of research and clinical data related to the conditions are consistent. Classification entails deciding which kinds of diagnostic entities should be recognized and how to order them in a meaningful way. Currently there are 3 major pain classification systems of relevance to orofacial pain: The International Association for the Study of Pain classification system, the International Headache Society classification system, and the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). All use different methodologies, and only the RDC/TMD take into account social and psychologic factors in the classification of conditions. Classification systems need to be reliable, valid, comprehensive, generalizable, and flexible, and they need to be tested using consensus views of experts as well as the available literature. There is an urgent need for a robust classification system for neuropathic trigeminal pain.

  17. Three-dimensional counting of morphologically normal human red blood cells via digital holographic microscopy

    NASA Astrophysics Data System (ADS)

    Yi, Faliu; Moon, Inkyu; Lee, Yeon H.

    2015-01-01

    Counting morphologically normal cells in human red blood cells (RBCs) is extremely beneficial in the health care field. We propose a three-dimensional (3-D) classification method of automatically determining the morphologically normal RBCs in the phase image of multiple human RBCs that are obtained by off-axis digital holographic microscopy (DHM). The RBC holograms are first recorded by DHM, and then the phase images of multiple RBCs are reconstructed by a computational numerical algorithm. To design the classifier, the three typical RBC shapes, which are stomatocyte, discocyte, and echinocyte, are used for training and testing. Nonmain or abnormal RBC shapes different from the three normal shapes are defined as the fourth category. Ten features, including projected surface area, average phase value, mean corpuscular hemoglobin, perimeter, mean corpuscular hemoglobin surface density, circularity, mean phase of center part, sphericity coefficient, elongation, and pallor, are extracted from each RBC after segmenting the reconstructed phase images by using a watershed transform algorithm. Moreover, four additional properties, such as projected surface area, perimeter, average phase value, and elongation, are measured from the inner part of each cell, which can give significant information beyond the previous 10 features for the separation of the RBC groups; these are verified in the experiment by the statistical method of Hotelling's T-square test. We also apply the principal component analysis algorithm to reduce the dimension number of variables and establish the Gaussian mixture densities using the projected data with the first eight principal components. Consequently, the Gaussian mixtures are used to design the discriminant functions based on Bayesian decision theory. To improve the performance of the Bayes classifier and the accuracy of estimation of its error rate, the leaving-one-out technique is applied. Experimental results show that the proposed method can

  18. Pulse wave imaging in normal, hypertensive and aneurysmal human aortas in vivo: a feasibility study

    NASA Astrophysics Data System (ADS)

    Li, Ronny X.; Luo, Jianwen; Balaram, Sandhya K.; Chaudhry, Farooq A.; Shahmirzadi, Danial; Konofagou, Elisa E.

    2013-07-01

    Arterial stiffness is a well-established biomarker for cardiovascular risk, especially in the case of hypertension. The progressive stages of an abdominal aortic aneurysm (AAA) have also been associated with varying arterial stiffness. Pulse wave imaging (PWI) is a noninvasive, ultrasound imaging-based technique that uses the pulse wave-induced arterial wall motion to map the propagation of the pulse wave and measure the regional pulse wave velocity (PWV) as an index of arterial stiffness. In this study, the clinical feasibility of PWI was evaluated in normal, hypertensive, and aneurysmal human aortas. Radiofrequency-based speckle tracking was used to estimate the pulse wave-induced displacements in the abdominal aortic walls of normal (N = 15, mean age 32.5 ± 10.2 years), hypertensive (N = 13, mean age 60.8 ± 15.8 years), and aneurysmal (N = 5, mean age 71.6 ± 11.8 years) human subjects. Linear regression of the spatio-temporal variation of the displacement waveform in the anterior aortic wall over a single cardiac cycle yielded the slope as the PWV and the coefficient of determination r2 as an approximate measure of the pulse wave propagation uniformity. The aortic PWV measurements in all normal, hypertensive, and AAA subjects were 6.03 ± 1.68, 6.69 ± 2.80, and 10.54 ± 6.52 m s-1, respectively. There was no significant difference (p = 0.15) between the PWVs of the normal and hypertensive subjects while the PWVs of the AAA subjects were significantly higher (p < 0.001) compared to those of the other two groups. Also, the average r2 in the AAA subjects was significantly lower (p < 0.001) than that in the normal and hypertensive subjects. These preliminary results suggest that the regional PWV and the pulse wave propagation uniformity (r2) obtained using PWI, in addition to the PWI images and spatio-temporal maps that provide qualitative visualization of the pulse wave, may potentially provide valuable information for the clinical characterization of aneurysms

  19. Analysis of normal human retinal vascular network architecture using multifractal geometry

    PubMed Central

    Ţălu, Ştefan; Stach, Sebastian; Călugăru, Dan Mihai; Lupaşcu, Carmen Alina; Nicoară, Simona Delia

    2017-01-01

    AIM To apply the multifractal analysis method as a quantitative approach to a comprehensive description of the microvascular network architecture of the normal human retina. METHODS Fifty volunteers were enrolled in this study in the Ophthalmological Clinic of Cluj-Napoca, Romania, between January 2012 and January 2014. A set of 100 segmented and skeletonised human retinal images, corresponding to normal states of the retina were studied. An automatic unsupervised method for retinal vessel segmentation was applied before multifractal analysis. The multifractal analysis of digital retinal images was made with computer algorithms, applying the standard box-counting method. Statistical analyses were performed using the GraphPad InStat software. RESULTS The architecture of normal human retinal microvascular network was able to be described using the multifractal geometry. The average of generalized dimensions (Dq) for q=0, 1, 2, the width of the multifractal spectrum (Δα=αmax − αmin) and the spectrum arms' heights difference (|Δf|) of the normal images were expressed as mean±standard deviation (SD): for segmented versions, D0=1.7014±0.0057; D1=1.6507±0.0058; D2=1.5772±0.0059; Δα=0.92441±0.0085; |Δf|= 0.1453±0.0051; for skeletonised versions, D0=1.6303±0.0051; D1=1.6012±0.0059; D2=1.5531±0.0058; Δα=0.65032±0.0162; |Δf|= 0.0238±0.0161. The average of generalized dimensions (Dq) for q=0, 1, 2, the width of the multifractal spectrum (Δα) and the spectrum arms' heights difference (|Δf|) of the segmented versions was slightly greater than the skeletonised versions. CONCLUSION The multifractal analysis of fundus photographs may be used as a quantitative parameter for the evaluation of the complex three-dimensional structure of the retinal microvasculature as a potential marker for early detection of topological changes associated with retinal diseases. PMID:28393036

  20. Integrated Transcriptome Map Highlights Structural and Functional Aspects of the Normal Human Heart.

    PubMed

    Caracausi, Maria; Piovesan, Allison; Vitale, Lorenza; Pelleri, Maria Chiara

    2017-04-01

    A systematic meta-analysis of the available gene expression profiling datasets for the whole normal human heart generated a quantitative transcriptome reference map of this organ. Transcriptome Mapper (TRAM) software integrated 32 gene expression profile datasets from different sources returning a reference value of expression for each of the 43,360 known, mapped transcripts assayed by any of the experimental platforms used in this regard. Main findings include the visualization at the gene and chromosomal levels of the classical description of the basic histology and physiology of the heart, the identification of suitable housekeeping reference genes, the analysis of stoichiometry of gene products, and the focusing on chromosome 21 genes, which are present in one excess copy in Down syndrome subjects, presenting cardiovascular defects in 30-40% of cases. Independent in vitro validation showed an excellent correlation coefficient (r = 0.98) with the in silico data. Remarkably, heart/non-cardiac tissue expression ratio may also be used to anticipate that effects of mutations will most probably affect or not the heart. The quantitative reference global portrait of gene expression in the whole normal human heart illustrates the structural and functional aspects of the whole organ and is a general model to understand the mechanisms underlying heart pathophysiology. J. Cell. Physiol. 232: 759-770, 2017. © 2016 Wiley Periodicals, Inc.

  1. Wound healing properties of ethyl acetate fraction of Moringa oleifera in normal human dermal fibroblasts

    PubMed Central

    Gothai, Sivapragasam; Arulselvan, Palanisamy; Tan, Woan Sean; Fakurazi, Sharida

    2016-01-01

    Background/Aim: Wounds are the outcome of injuries to the skin that interrupt the soft tissue. Healing of a wound is a complex and long-drawn-out process of tissue repair and remodeling in response to injury. A large number of plants are used by folklore traditions for the treatment of cuts, wounds and burns. Moringa oleifera (MO) is an herb used as a traditional folk medicine for the treatment of various skin wounds and associated diseases. The underlying mechanisms of wound healing activity of ethyl acetate fraction of MO leaves extract are completely unknown. Materials and Methods: In the current study, ethyl acetate fraction of MO leaves was investigated for its efficacy on cell viability, proliferation and migration (wound closure rate) in human normal dermal fibroblast cells. Results: Results revealed that lower concentration (12.5 µg/ml, 25 µg/ml, and 50 µg/ml) of ethyl acetate fraction of MO leaves showed remarkable proliferative and migratory effect on normal human dermal fibroblasts. Conclusion: This study suggested that ethyl acetate fraction of MO leaves might be a potential therapeutic agent for skin wound healing by promoting fibroblast proliferation and migration through increasing the wound closure rate corroborating its traditional use. PMID:27069722

  2. Using infrared and Raman microspectroscopies to compare ex vivo involved psoriatic skin with normal human skin.

    PubMed

    Leroy, Marie; Lefèvre, Thierry; Pouliot, Roxane; Auger, Michèle; Laroche, Gaétan

    2015-06-01

    Psoriasis is a chronic dermatosis that affects around 3% of the world's population. The etiology of this autoimmune pathology is not completely understood. The barrier function of psoriatic skin is known to be strongly altered, but the structural modifications at the origin of this dysfunction are not clear. To develop strategies to reduce symptoms of psoriasis or adequate substitutes for modeling, a deep understanding of the organization of psoriatic skin at a molecular level is required. Infrared and Raman microspectroscopies have been used to obtain direct molecular-level information on psoriatic and healthy human skin biopsies. From the intensities and positions of specific vibrational bands, the lipid and protein distribution and the lipid order have been mapped in the different layers of the skin. Results showed a similar distribution of lipids and collagen for normal and psoriatic human skin. However, psoriatic skin is characterized by heterogeneity in lipid/protein composition at the micrometer scale, a reduction in the definition of skin layer boundaries and a decrease in lipid chain order in the stratum corneum as compared to normal skin. A global decrease of the structural organization is exhibited in psoriatic skin that is compatible with an alteration of its barrier properties.

  3. Particle irradiation induces FGF2 expression in normal human lens cells

    NASA Technical Reports Server (NTRS)

    Chang, P. Y.; Bjornstad K, A.; Chang, E.; McNamara, M.; Barcellos-Hoff, M. H.; Lin, S. P.; Aragon, G.; Polansky, J. R.; Lui, G. M.; Blakely, E. A.

    2000-01-01

    Particle Irradiation Induces FGF2 Expression in Normal Human Lens Cells. Particle radiations, including both proton and helium-ion beams, have been used to successfully treat choroidal melanoma, but with the complication of radiation-induced cataract. We have investigated a role for radiation-induced changes in the expression of basic fibroblast growth factor (FGF2) gene expression as part of the mechanism(s) underlying lens cell injury associated with cataract. Normal human lens epithelial (HLE) cells were cultured in vitro on extracellular matrix (ECM) originated from bovine corneal endothelial cells. This study reports evidence for rapid but transient induction of FGF2 transcripts, an increase of between 5- and 8-fold, within 0.5 h after exposure to particle radiation, followed by another wave of increased transcription at 2-3 h postirradiation. Immunofluorescence results confirm the enhanced levels of FGF2 protein rapidly after exposure to protons or helium ions, followed by another wave of increased activity unique to helium at 6 h postirradiation. This second wave of increased immunoreactivity was not observed in the proton-irradiated samples. Total FGF2 protein analysis after helium-ion exposures shows induced expression of three FGF2 isoforms, with an increase of up to 2-fold in the 18-kDa low-molecular-weight species. Studies of the effects of protons on individual FGF2 protein isoforms are in progress. Several mechanisms involving a role for FGF2 in radiation-induced cataract are discussed.

  4. Detection of Apoptosis and Necrosis in Normal Human Lung Cells Using 1H NMR Spectroscopy

    NASA Astrophysics Data System (ADS)

    Shih, Chwen-Ming; Ko, Wun-Chang; Yang, Liang-Yo; Lin, Chien-Ju; Wu, Jui-Sheng; Lo, Tsui-Yun; Wang, Shwu-Huey; Chen, Chien-Tsu

    2005-05-01

    This study aimed to detect apoptosis and necrosis in MRC-5, a normal human lung cell line, by using noninvasive proton nuclear magnetic resonance (1H NMR). Live MRC-5 cells were processed first for 1H NMR spectroscopy; subsequently their types and the percentage of cell death were assessed on a flow cytometer. Cadmium (Cd) and mercury (Hg) induced apoptosis and necrosis in MRC-5 cells, respectively, as revealed by phosphatidylserine externalization on a flow cytometer. The spectral intensity ratio of methylene (CH2) resonance (at 1.3 ppm) to methyl (CH3) resonance (at 0.9 ppm) was directly proportional to the percentage of apoptosis and strongly and positively correlated with PI staining after Cd treatment (r2 = 0.9868, P < 0.01). In contrast, this ratio only increased slightly within 2-h Hg treatment, and longer Hg exposure failed to produce further increase. Following 2-h Hg exposure, the spectral intensity of choline resonance (at 3.2 ppm) was abolished, but this phenomenon was absent in Cd-induced apoptosis. These findings together demonstrate that 1H NMR is a novel tool with a quantitative potential to distinguish apoptosis from necrosis as early as the onset of cell death in normal human lung cells.

  5. Using infrared and Raman microspectroscopies to compare ex vivo involved psoriatic skin with normal human skin

    NASA Astrophysics Data System (ADS)

    Leroy, Marie; Lefèvre, Thierry; Pouliot, Roxane; Auger, Michèle; Laroche, Gaétan

    2015-06-01

    Psoriasis is a chronic dermatosis that affects around 3% of the world's population. The etiology of this autoimmune pathology is not completely understood. The barrier function of psoriatic skin is known to be strongly altered, but the structural modifications at the origin of this dysfunction are not clear. To develop strategies to reduce symptoms of psoriasis or adequate substitutes for modeling, a deep understanding of the organization of psoriatic skin at a molecular level is required. Infrared and Raman microspectroscopies have been used to obtain direct molecular-level information on psoriatic and healthy human skin biopsies. From the intensities and positions of specific vibrational bands, the lipid and protein distribution and the lipid order have been mapped in the different layers of the skin. Results showed a similar distribution of lipids and collagen for normal and psoriatic human skin. However, psoriatic skin is characterized by heterogeneity in lipid/protein composition at the micrometer scale, a reduction in the definition of skin layer boundaries and a decrease in lipid chain order in the stratum corneum as compared to normal skin. A global decrease of the structural organization is exhibited in psoriatic skin that is compatible with an alteration of its barrier properties.

  6. Raman spectroscopy of DNA packaging in individual human sperm cells distinguishes normal from abnormal cells.

    PubMed

    Huser, Thomas; Orme, Christine A; Hollars, Christopher W; Corzett, Michele H; Balhorn, Rod

    2009-05-01

    Healthy human males produce sperm cells of which about 25-40% have abnormal head shapes. Increases in the percentage of sperm exhibiting aberrant sperm head morphologies have been correlated with male infertility, and biochemical studies of pooled sperm have suggested that sperm with abnormal shape may contain DNA that has not been properly repackaged by protamine during spermatid development. We have used micro-Raman spectroscopy to obtain Raman spectra from individual human sperm cells and examined how differences in the Raman spectra of sperm chromatin correlate with cell shape. We show that Raman spectra of individual sperm cells contain vibrational marker modes that can be used to assess the efficiency of DNA-packaging for each cell. Raman spectra obtained from sperm cells with normal shape provide evidence that DNA in these sperm is very efficiently packaged. We find, however, that the relative protein content per cell and DNA packaging efficiencies are distributed over a relatively wide range for sperm cells with both normal and abnormal shape. These findings indicate that single cell Raman spectroscopy should be a valuable tool in assessing the quality of sperm cells for in-vitro fertilization.

  7. Raman Spectroscopy of DNA Packaging in Individual Human Sperm Cells distinguishes Normal from Abnormal Cells

    SciTech Connect

    Huser, T; Orme, C; Hollars, C; Corzett, M; Balhorn, R

    2009-03-09

    Healthy human males produce sperm cells of which about 25-40% have abnormal head shapes. Increases in the percentage of sperm exhibiting aberrant sperm head morphologies have been correlated with male infertility, and biochemical studies of pooled sperm have suggested that sperm with abnormal shape may contain DNA that has not been properly repackaged by protamine during spermatid development. We have used micro-Raman spectroscopy to obtain Raman spectra from individual human sperm cells and examined how differences in the Raman spectra of sperm chromatin correlate with cell shape. We show that Raman spectra of individual sperm cells contain vibrational marker modes that can be used to assess the efficiency of DNA-packaging for each cell. Raman spectra obtained from sperm cells with normal shape provide evidence that DNA in these sperm is very efficiently packaged. We find, however, that the relative protein content per cell and DNA packaging efficiencies are distributed over a relatively wide range for sperm cells with both normal and abnormal shape. These findings indicate that single cell Raman spectroscopy should be a valuable tool in assessing the quality of sperm cells for in-vitro fertilization.

  8. The Fate of a Normal Human Cell Traversed by a Single Charged Particle

    NASA Astrophysics Data System (ADS)

    Fournier, C.; Zahnreich, S.; Kraft, D.; Friedrich, T.; Voss, K.-O.; Durante, M.; Ritter, S.

    2012-09-01

    The long-term ``fate'' of normal human cells after single hits of charged particles is one of the oldest unsolved issues in radiation protection and cellular radiobiology. Using a high-precision heavy-ion microbeam we could target normal human fibroblasts with exactly one or five carbon ions and measured the early cytogenetic damage and the late behaviour using single-cell cloning. Around 70% of the first cycle cells presented visible aberrations in mFISH after a single ion traversal, and about 5% of the cells were still able to form colonies. In one third of selected high-proliferative colonies we observed clonal (radiation-induced) aberrations. Terminal differentiation and markers of senescence (PCNA, p16) in the descendants of cells traversed by one carbon ion occurred earlier than in controls, but no evidence of radiation-induced chromosomal instability was found. We conclude that cells surviving single-ion traversal, often carrying clonal chromosome aberrations, undergo accelerated senescence but maintain chromosomal stability.

  9. [Transformation of trigeminal nerve tumor into malignant peripheral nerve sheath tumor (MPNST)].

    PubMed

    Nenashev, E A; Cherekaev, V A; Kadasheva, A B; Kozlov, A V; Rotin, D L; Stepanian, M A

    2012-01-01

    Malignant peripheral nerve sheath tumor (MPNST) is a rare entity with only 18 cases of trigeminal nerve MPNST described by now and only one report of malignant transformation of trigeminal nerve tumor into MPNST published up to date. One more case of malignant transformation of trigeminal nerve (1st division) tumor into MPNST is demonstrated.

  10. Relationship between electrophysiological signature and defined sensory modality of trigeminal ganglion neurons in vivo.

    PubMed

    Boada, M Danilo

    2013-02-01

    The trigeminal ganglia (TG) innervate a heterogeneous set of highly sensitive and exposed tissues. Weak, innocuous stimuli can evoke pain as a normal response in some areas such as the cornea. This observation implies, however, the capability of low-threshold mechanoreceptors, inducing pain in the normal condition. To clarify this matter, the present study correlates the electrical signature (both fiber conduction velocity and somatic electrical properties) with receptor field, mechanical threshold, and temperature responsiveness of sensory afferents innervating tissues with dissimilar sensitivity (skin vs. cornea) in the trigeminal domain. Intracellular recordings were obtained in vivo from 148 neurons of the left TG of 62 mice. In 111 of these neurons, the peripheral receptor field was successfully localized: 96 of them innervated the hairy skin, while the remaining 15 innervated the cornea. The electrical signature was defined and peripheral responses correlated with tissue target. No high threshold neurons were found in the cornea. Moreover, the electrical signature of corneal afferents resembles nociceptive neurons in the skin. TG skin afferents showed similar membrane electrical signature and sensory modality as skin afferents from dorsal root ganglion, although TG afferents exhibited a shorter duration of afterhyperpolarization then those previously described in dorsal root ganglion. These data suggest than new or different ways to classify and study TG sensory neurons may be required.

  11. Investigation of normal human skin tissue and acupuncture points of human skin tissue using fiberoptical FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Brooks, Angelique L.; Bruch, Reinhard F.; Afanasyeva, Natalia I.; Kolyakov, Sergei F.; Butvina, Leonid N.; Ma, Lixing

    1998-06-01

    An innovative spectroscopic diagnostic method has been developed for investigation of different regions of normal human skin tissue. This new method is a combination of Fourier transform IR fiberoptic evanescent wave (FTIR-FEW) spectroscopy and fiber optic techniques for the middle IR (MIR) wavelength range. The fiber optical sensors we have used are characterized by low optical losses and high flexibility for remote analysis. Our fiber optical accessories and method allows for direct interaction of the skin tissue with the fiber probe and can be utilized with a diversity of standard commercial Fourier transform spectrometers. The FTIR-FEW technique, using nontoxic unclad fibers in the attenuated total reflection regime, is suitable for noninvasive, fast, sensitive investigations of normal skin in vivo for various medical diagnostics applications including studies of acupuncture points. Here we present the first data on IR spectra of skin tissue in vivo for normal skin and several acupuncture points in the range of 1300 to 1800 cm-1 and 2600 to 4000 cm-1.

  12. Validation of Normal Human Bronchial Epithelial Cells as a Model for Influenza A Infections in Human Distal Trachea

    PubMed Central

    Davis, A. Sally; Chertow, Daniel S.; Moyer, Jenna E.; Suzich, Jon; Sandouk, Aline; Dorward, David W.; Logun, Carolea; Shelhamer, James H.

    2015-01-01

    Primary normal human bronchial/tracheal epithelial (NHBE) cells, derived from the distal-most aspect of the trachea at the bifurcation, have been used for a number of studies in respiratory disease research. Differences between the source tissue and the differentiated primary cells may impact infection studies based on this model. Therefore, we examined how well-differentiated NHBE cells compared with their source tissue, the human distal trachea, as well as the ramifications of these differences on influenza A viral pathogenesis research using this model. We employed a histological analysis including morphological measurements, electron microscopy, multi-label immunofluorescence confocal microscopy, lectin histochemistry, and microarray expression analysis to compare differentiated NHBEs to human distal tracheal epithelium. Pseudostratified epithelial height, cell type variety and distribution varied significantly. Electron microscopy confirmed differences in cellular attachment and paracellular junctions. Influenza receptor lectin histochemistry revealed that α2,3 sialic acids were rarely present on the apical aspect of the differentiated NHBE cells, but were present in low numbers in the distal trachea. We bound fluorochrome bioconjugated virus to respiratory tissue and NHBE cells and infected NHBE cells with human influenza A viruses. Both indicated that the pattern of infection progression in these cells correlated with autopsy studies of fatal cases from the 2009 pandemic. PMID:25604814

  13. Regulation of pigmentation by substrate elasticity in normal human melanocytes and melanotic MNT1 human melanoma cells.

    PubMed

    Choi, Hyunjung; Kim, Mina; Ahn, Song Ih; Cho, Eun-Gyung; Lee, Tae Ryong; Shin, Jennifer H

    2014-03-01

    The elasticity of the cellular microenvironment is a key regulator of cellular physiology in many cell types. To investigate the effects of substrate stiffness on the pigmentation process, we cultured normal human melanocytes (NHM) and MNT1 melanoma cells on laminin-coated polydimethylsiloxane (PDMS) substrates of different stiffness. The dendricity of NHM and MNT1 cells was reduced as the substrate stiffness decreased, and the degree of melanosome transfer from NHM or MNT1 cells to normal human keratinocytes was decreased on softer substrates with the reduced dendricity. Gene and protein expressions of MITF, tyrosinase, TRP2, and gp100/PMEL17 exhibited a consistent decreasing trend with the decreasing stiffness. Because the stiffness sensing is mediated by focal adhesion complex through integrin receptors, we checked laminin specific integrin alpha 6 and p-FAK for MNT1 cells to observe that the substrate adhesion was weakened as the substrate stiffness decreased. Weaker adhesion on a softer substrate was accompanied by dynamic shape changes in MNT1 cells with higher speed and larger scattering. Dendritic MNT1 cells cultured on a stiffer substrate exhibited lower migration with smaller root mean squared displacement. These results demonstrate the possibility that skin pigmentation can be influenced by mechanical properties of the cellular microenvironment and can increase when the skin becomes stiff.

  14. Pharmacological versus microvascular decompression approaches for the treatment of trigeminal neuralgia: clinical outcomes and direct costs

    PubMed Central

    Lemos, Laurinda; Alegria, Carlos; Oliveira, Joana; Machado, Ana; Oliveira, Pedro; Almeida, Armando

    2011-01-01

    In idiopathic trigeminal neuralgia (TN) the neuroimaging evaluation is usually normal, but in some cases a vascular compression of trigeminal nerve root is present. Although the latter condition may be referred to surgery, drug therapy is usually the first approach to control pain. This study compared the clinical outcome and direct costs of (1) a traditional treatment (carbamazepine [CBZ] in monotherapy [CBZ protocol]), (2) the association of gabapentin (GBP) and analgesic block of trigger-points with ropivacaine (ROP) (GBP+ROP protocol), and (3) a common TN surgery, microvascular decompression of the trigeminal nerve (MVD protocol). Sixty-two TN patients were randomly treated during 4 weeks (CBZ [n = 23] and GBP+ROP [n = 17] protocols) from cases of idiopathic TN, or selected for MVD surgery (n = 22) due to intractable pain. Direct medical cost estimates were determined by the price of drugs in 2008 and the hospital costs. Pain was evaluated using the Numerical Rating Scale (NRS) and number of pain crises; the Hospital Anxiety and Depression Scale, Sickness Impact Profile, and satisfaction with treatment and hospital team were evaluated. Assessments were performed at day 0 and 6 months after the beginning of treatment. All protocols showed a clinical improvement of pain control at month 6. The GBP+ROP protocol was the least expensive treatment, whereas surgery was the most expensive. With time, however, GBP+ROP tended to be the most and MVD the least expensive. No sequelae resulted in any patient after drug therapies, while after MDV surgery several patients showed important side effects. Data reinforce that, (1) TN patients should be carefully evaluated before choosing therapy for pain control, (2) different pharmacological approaches are available to initiate pain control at low costs, and (3) criteria for surgical interventions should be clearly defined due to important side effects, with the initial higher costs being strongly reduced with time. PMID:21941455

  15. Antibacterial potential and genetic profile of Enterococcus faecium strains isolated from human normal flora.

    PubMed

    Karimaei, Samira; Sadeghi, Javad; Asadian, Mahla; Esghaei, Maryam; Pourshafie, Mohammad Reza; Talebi, Malihe

    2016-07-01

    Enterococci have a widespread attendance in the circumference and belongs to the enteric commensal microbiota. Most of them produce the antimicrobial compounds and have an inhibition effect on pathogenic microorganisms. The objective of this study was to characterize the enterococcal strains isolated from human normal flora and assess their antibacterial activity. Enterococcal isolates were obtained from the feces of eighteen healthy humans. All enterococcal species were identified by biochemical and species-specific polymerase chain reaction (PCR). These isolates were investigated further to examine their ability to inhibit growth of Salmonella typhi, Shigella flexneri and Escherichia coli by well diffusion assay. Furthermore, antibiotic susceptibility test was performed and genetic relatedness of all isolates was evaluated by Pulse Field Gel Electrophoresis (PFGE). In all, 432 isolates were obtained from fecal samples. All of the isolates identified as Enterococcus faecium by biochemical and molecular (PCR) methods. Using repetitive element palindromic (REP)-PCR method 54 patterns have been obtained and were selected for further evaluation. The results indicated that 66%, 38% and 24% of our isolates had antimicrobial effect against S. typhi, S flexneri and enteroaggregative Escherichia coli (EAEC), respectively. On the other hand, there was no significant inhibition effect against enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli (ETEC). All isolates were sensitive to vancomycin, teicoplanin, linezolid, ampicillin, chloramphenicol and gentamicin. On the other hand, the resistance rates for erythromycin, tetracycline and ciprofloxacin were 20%, 22%, and 1.8% respectively. In addition, the analysis of PFGE showed forty patterns with eight (40.7%) common types (CT) and thirty two (59.2%) single types (ST). Among eight common types, only one common type (CT5) had similar antimicrobial effect. These results suggested that enterococcal isolates obtained from

  16. Rejoining of isochromatid breaks induced by heavy ions in G2-phase normal human fibroblasts

    NASA Technical Reports Server (NTRS)

    Kawata, T.; Durante, M.; Furusawa, Y.; George, K.; Ito, H.; Wu, H.; Cucinotta, F. A.

    2001-01-01

    We reported previously that exposure of normal human fibroblasts in G2 phase of the cell cycle to high-LET radiation produces a much higher frequency of isochromatid breaks than exposure to gamma rays. We concluded that an increase in the production of isochromatid breaks is a signature of initial high-LET radiation-induced G2-phase damage. In this paper, we report the repair kinetics of isochromatid breaks induced by high-LET radiation in normal G2-phase human fibroblasts. Exponentially growing human fibroblasts (AG1522) were irradiated with gamma rays or energetic carbon (290 MeV/nucleon), silicon (490 MeV/nucleon), or iron (200 MeV/nucleon) ions. Prematurely condensed chromosomes were induced by calyculin A after different postirradiation incubation times ranging from 0 to 600 min. Chromosomes were stained with Giemsa, and aberrations were scored in cells at G2 phase. G2-phase fragments, the result of the induction of isochromatid breaks, decreased quickly with incubation time. The curve for the kinetics of the rejoining of chromatid-type breaks showed a slight upward curvature with time after exposure to 440 keV/microm iron particles, probably due to isochromatid-isochromatid break rejoining. The formation of chromatid exchanges after exposure to high-LET radiation therefore appears to be underestimated, because isochromatid-isochromatid exchanges cannot be detected. Increased induction of isochromatid breaks and rejoining of isochromatid breaks affect the overall kinetics of chromatid-type break rejoining after exposure to high-LET radiation.

  17. Monoclonal Antibodies Detect a Spectrin-Like Protein in Normal and Dystrophic Human Skeletal Muscle

    NASA Astrophysics Data System (ADS)

    Appleyard, S. T.; Dunn, M. J.; Dubowitz, V.; Scott, M. L.; Pittman, S. J.; Shotton, D. M.

    1984-02-01

    Spectrin is the major protein of the erythrocyte membrane skeleton, which is bound to the cytoplasmic surface of the membrane's lipid bilayer and is responsible for cell shape and membrane elasticity. Inability to identify spectrin in other cell types led to the assumption that this protein was unique to erythrocytes. However, spectrin-like proteins have been demonstrated recently in a variety of cell types, including skeletal and cardiac muscle, in several species. We used monoclonal antibodies against human erythrocyte spectrin subunits in an immunocytochemical study to detect related proteins in normal and diseased human skeletal muscle. Six of seven monoclonal antibodies against β -spectrin determinants were bound at the cytoplasmic surface of muscle fiber plasma membranes, whereas none of six monoclonal antibodies against α -spectrin determinants was bound. Muscle fibers of patients with neuromuscular diseases showed similar distribution and specificity of antibody binding to those of normal subjects, but the intensity of binding was increased. In contrast, probable regenerating fibers in muscle of patients with muscular dystrophies showed reduced binding of antibodies, but reduced binding was not seen in fetal muscle fibers nor in those of a patient with a myotubular myopathy. We conclude that human skeletal muscle fibers possess a spectrin-related protein associated with their plasma membrane that shows extensive β -chain similarities to erythrocyte spectrin but differs significantly with respect to the α -subunit. Its function may be associated with the maintenance of membrane and myofibril integrity during contraction, and the increased antibody binding in diseased muscle may reflect a structural rearrangement of spectrin or a compensatory increase in spectrin abundance in response to increased stress on these systems.

  18. Hydrogen sulfide determines HNO-induced stimulation of trigeminal afferents.

    PubMed

    Wild, Vanessa; Messlinger, Karl; Fischer, Michael J M

    2015-08-18

    Endogenous NO and hydrogen sulfide form HNO, which causes CGRP release via TRPA1 channel activation in sensory nerves. In the present study, stimulation of intact trigeminal afferent neuron preparations with NO donors, Na2S or both was analyzed by measuring CGRP release as an index of mass activation. Combined stimulation was able to activate all parts of the trigeminal system and acted synergistic compared to stimulation with both substances alone. To investigate the contribution of both substances, we varied their ratio and tracked intracellular calcium in isolated neurons. Our results demonstrate that hydrogen sulfide is the rate-limiting factor for HNO formation. CGRP has a key role in migraine pathophysiology and HNO formation at all sites of the trigeminal system should be considered for this novel means of activation.

  19. Acupuncture for episodic cluster headache: a trigeminal approach.

    PubMed

    Hayhoe, Simon

    2015-09-10

    Following evidence that acupuncture is clinically feasible and cost-effective in the treatment of headache, the UK National Institute for Health and Care Excellence recommends acupuncture as prophylactic treatment for migraine and tension headache. There has thus been expectation that other forms of headache should benefit also. Unfortunately, acupuncture has not generally been successful for cluster headache. This may be due to acupuncturists approaching the problem as one of severe migraine. In fact, cluster headache is classed as a trigeminal autonomic cephalgia. In this case report, episodic cluster headache is treated in the same way as has been shown effective for trigeminal neuralgia. Acupuncture is applied to the contralateral side at points appropriate for stimulating branches of the trigeminal nerve. Thus, ST2 is used for the infraorbital nerve, BL2 and Yuyao for the supratrochlear and supraorbital nerves, and Taiyang for the temporal branch of the zygomatic nerve.

  20. Evidence for a novel bursting mechanism in rodent trigeminal neurons.

    PubMed Central

    Del Negro, C A; Hsiao, C F; Chandler, S H; Garfinkel, A

    1998-01-01

    We investigated bursting behavior in rodent trigeminal neurons. The essential mechanisms operating in the biological systems were determined based on testable predictions of mathematical models. Bursting activity in trigeminal motoneurons is consistent with a traditional mechanism employing a region of negative slope resistance in the steady-state current-voltage relationship (Smith, T. G. 1975. Nature. 253:450-452). However, the bursting dynamics of trigeminal interneurons is inconsistent with the traditional mechanisms, and is far more effectively explained by a new model of bursting that exploits the unique stability properties associated with spike threshold (Baer, S. M., T. Erneux, and J. Rinzel. 1989. SIAM J. Appl. Math. 49:55-71). PMID:9649377

  1. Evaluation of algorithm methods for fluorescence spectra of cancerous and normal human tissues

    NASA Astrophysics Data System (ADS)

    Pu, Yang; Wang, Wubao; Alfano, Robert R.

    2016-03-01

    The paper focus on the various algorithms on to unravel the fluorescence spectra by unmixing methods to identify cancerous and normal human tissues from the measured fluorescence spectroscopy. The biochemical or morphologic changes that cause fluorescence spectra variations would appear earlier than the histological approach; therefore, fluorescence spectroscopy holds a great promise as clinical tool for diagnosing early stage of carcinomas and other deceases for in vivo use. The method can further identify tissue biomarkers by decomposing the spectral contributions of different fluorescent molecules of interest. In this work, we investigate the performance of blind source un-mixing methods (backward model) and spectral fitting approaches (forward model) in decomposing the contributions of key fluorescent molecules from the tissue mixture background when certain selected excitation wavelength is applied. Pairs of adenocarcinoma as well as normal tissues confirmed by pathologist were excited by selective wavelength of 340 nm. The emission spectra of resected fresh tissue were used to evaluate the relative changes of collagen, reduced nicotinamide adenine dinucleotide (NADH), and Flavin by various spectral un-mixing methods. Two categories of algorithms: forward methods and Blind Source Separation [such as Principal Component Analysis (PCA) and Independent Component Analysis (ICA), and Nonnegative Matrix Factorization (NMF)] will be introduced and evaluated. The purpose of the spectral analysis is to discard the redundant information which conceals the difference between these two types of tissues, but keep their diagnostically significance. The facts predicted by different methods were compared to the gold standard of histopathology. The results indicate that these key fluorophores within tissue, e.g. tryptophan, collagen, and NADH, and flavin, show differences of relative contents of fluorophores among different types of human cancer and normal tissues. The

  2. Enhancement of ’In Vitro’ Granulocyte-Macrophage Colony Formation by Normal Human Serum or Plasma

    DTIC Science & Technology

    1976-08-01

    the CSA dose - response curve . . .. 10 LIST OF TABLES Table 1. Enhancement of Human and Murine In Vitro Bone Marrow Colony Formation by Normal Hluman...presence of NUS. *-, Dose - response curve for murine bone marrow colony formation using PMUE as a source of CSA. --- Dose - response curve for human...bone marrow colony for- mation using human peripheral blood leukocytes as a source of CSA. o---o Partial dose - response curve for human bone mar- row

  3. Local tissue growth patterns underlying normal fetal human brain gyrification quantified in utero

    PubMed Central

    Rajagopalan, Vidya; Scott, Julia; Habas, Piotr A.; Kim, Kio; Corbett-Detig, James; Rousseau, Francois; Barkovich, A. James; Glenn, Orit A.; Studholme, Colin

    2011-01-01

    Existing knowledge of growth patterns in the living fetal human brain is based upon in utero imaging studies by MRI and ultrasound, which describe overall growth and provided mainly qualitative findings. However, formation of the complex folded cortical structure of the adult brain requires, in part, differential rates of regional tissue growth. To better understand these local tissue growth patterns, we applied recent advances in fetal MRI motion correction and computational image analysis techniques to 40 normal fetal human brains covering a period of primary sulcal formation (20-28 gestational weeks). Growth patterns were mapped by quantifying tissue locations that were expanding more or less quickly than the overall cerebral growth rate, which reveal increasing structural complexity. We detected increased local relative growth rates in the formation of the pre- and post-central gyri, right superior temporal gyrus and opercula, which differentiated between the constant growth rate in underlying cerebral mantle and the accelerating rate in the cortical plate undergoing folding. Analysis focused on the cortical plate revealed greater volume increases in parietal and occipital regions compared to the frontal lobe. Cortical plate growth patterns constrained to narrower age ranges showed that gyrification, reflected by greater growth rates, was more pronounced after 24 gestational weeks. Local hemispheric volume asymmetry was located in the posterior peri-Sylvian area associated with structural lateralization in the mature brain. These maps of fetal brain growth patterns construct a spatially specific baseline of developmental biomarkers with which to correlate abnormal development in the human. PMID:21414909

  4. The patterns and expression of KDR in normal tissues of human internal organs.

    PubMed

    Huang, Jianfei; Zhu, Huijun; Wang, Xudong; Tang, Qi; Huang, Hua; Wu, Kerong; Zhu, Jin; Feng, Zhenqing; Shi, Gongshen

    2011-12-01

    KDR has been implicated for playing an important role in the formation of new blood vessels and in solid tumor growth. It was considered as one of the most important regulators of angiogenesis and a key target in anticancer treatment. In the present study, we characterized KDR mRNA and protein expression in normal tissues of perinatal and adult tissues using One-step Real-Time RT-PCR and immunohistochemistry with a self-made anti-KDR antibody. The expression of KDR mRNA and protein in perinatal internal organs were all higher than in adult organs including brain, kidney, liver, lung and heart, respectively. KDR protein was presented in the cell plasma membrane of human internal tissues. The expression of KDR protein was raised in macrophage of spleen, and decreased in neurons of brain, myocardium, bronchial epithelial cells and alveolar epithelial cell, proximal and distal tubules cells, and hepatic cells with the maturity process of human organs. Notably, the order of KDR protein expression from highest to lowest is as follows: brain, liver, heart, kidney, and lung in adult tissues with statistically significant. It follows that how to balance the potential therapeutic side effect with human internal organs in targeted therapy of over-expressing KDR tumor.

  5. Lactobacillus sakei lipoteichoic acid inhibits MMP-1 induced by UVA in normal dermal fibroblasts of human.

    PubMed

    You, Ga-Eun; Jung, Bong-Jun; Kim, Hye-Rim; Kim, Han-Geun; Kim, Tae-Rahk; Chung, Dae-Kyun

    2013-10-28

    Human skin is continuously exposed to ultraviolet (UV)-induced photoaging. UVA increases the activity of MMP-1 in dermal fibroblasts through mitogen-activated protein kinase (MAPK), p38, signaling. The irradiation of keratinocytes by UVA results in the secretion of the inflammatory cytokine, tumor necrosis factor-α (TNF-α), and the stimulation of MMP-1 in normal human dermal fibroblasts (NHDFs). Lipoteichoic acid (LTA) is a component of the cell wall of gram-positive Lactobacillus spp. of bacteria. LTA is well known as an anti-inflammation molecule. LTA of the bacterium Lactobacillus plantarum has an anti-photoaging effect, but the potential anti-photoaging effect of the other bacteria has not been examined to date. The current study showed that L. sakei LTA (sLTA) has an immune modulating effect in human monocyte cells. Our object was whether inhibitory effects of sLTA on MMP-1 are caused from reducing the MAPK signal in NHDFs. It inhibits MMP-1 and MAPK signaling induced by UVA in NHDFs. We also confirmed effects of sLTA suppressing TNF-α inducing MMP-1 in NHDFs.

  6. Propagation of normal human epithelial cell populations using an in vivo culture system. Description and applications.

    PubMed Central

    Klein-Szanto, A. J.; Terzaghi, M.; Mirkin, L. D.; Martin, D.; Shiba, M.

    1982-01-01

    A new model using xenotransplanted human epithelia was developed for the study of toxic and carcinogenic effects of chemicals. Epithelial cells from the respiratory tract of 4 male and 3 female premature and fullterm fetuses were enzymatically removed and inoculated into deepithelialized rat tracheas. These were sealed at both ends and transplanted subcutaneously into nude mice. After 3-4 weeks, a normal mucociliary epithelium covered the tracheal lumen. At this stage the epithelial cells could be isolated again and transplanted into new denuded rat tracheas. This passaging could be repeated up to six times, each permitting an amplification factor of approximately 3. Tracheal transplants containing cells of human origin (in vivo Passages 2-4) were treated with 7,12-dimethylbenz(a)anthracene. Hyperplasias, squamous metaplasias, and dysplasias were seen 1-8 weeks after initiation of treatment, indicating that the responses of human and rodent epithelial cells to polycyclic aromatic hydrocarbons are similar. Initial experiments with skin and esophageal epithelia suggest that other covering epithelia could also be used in this fashion for evaluation of toxicants and carcinogens that are likely to come into contact with these tissues. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:6821529

  7. Transfection of normal human bronchial epithelial cells with the bcl-2 oncogene

    SciTech Connect

    Kennedy, C.H.; Kenyon, K.D.; Tesfaigzi, J.

    1995-12-01

    In vitro, studies examining the transformation of virus-immortalized human bronchial epithelial (HBE) cells after exposure to chemical and physical carcinogens have contributed to our understanding of the mechanisms that underlie the development of lung cancer. Virus-immortalized HBE cells have been used because of both the limited life span of normal human bronchial epithelial (NHBE) cells in culture (approximately 30-35 population doublins) and their resistance to in vitro malignant transformation. For example, human papillomavirus (HPV)-immortalized HBE cells have been used to study the genetic changes that occur after exposure to {alpha}-particles in vitro. Although this model may prove to be useful for studying the 18% or less of bronchogenic carcinomas found to contain HPV sequences, it is not an appropriate model for studying the majority of lung epithelial malignancies in which HPV DNA is not detected. This view is supported by the fact that HPV-immortalized cell lines commonly exhibit aneuploidy. This results of this study suggest that: (1) NHBE cells can be transiently transfected with the pCMV{Beta} vector; and (2) the antibiotic hygromycin-resistant transfected cells.

  8. Global differential expression of genes located in the Down Syndrome Critical Region in normal human brain

    PubMed Central

    Montoya, Julio Cesar; Fajardo, Dianora; Peña, Angela; Sánchez, Adalberto; Domínguez, Martha C; Satizábal, José María

    2014-01-01

    Background: The information of gene expression obtained from databases, have made possible the extraction and analysis of data related with several molecular processes involving not only in brain homeostasis but its disruption in some neuropathologies; principally in Down syndrome and the Alzheimer disease. Objective: To correlate the levels of transcription of 19 genes located in the Down Syndrome Critical Region (DSCR) with their expression in several substructures of normal human brain. Methods: There were obtained expression profiles of 19 DSCR genes in 42 brain substructures, from gene expression values available at the database of the human brain of the Brain Atlas of the Allen Institute for Brain Sciences", (http://human.brain-map.org/). The co-expression patterns of DSCR genes in brain were calculated by using multivariate statistical methods. Results: Highest levels of gene expression were registered at caudate nucleus, nucleus accumbens and putamen among central areas of cerebral cortex. Increased expression levels of RCAN1 that encode by a protein involved in signal transduction process of the CNS were recorded for PCP4 that participates in the binding to calmodulin and TTC3; a protein that is associated with differentiation of neurons. That previously identified brain structures play a crucial role in the learning process, in different class of memory and in motor skills. Conclusion: The precise regulation of DSCR gene expression is crucial to maintain the brain homeostasis, especially in those areas with high levels of gene expression associated with a remarkable process of learning and cognition. PMID:25767303

  9. Radioprotective Effect of Achillea millefolium L Against Genotoxicity Induced by Ionizing Radiation in Human Normal Lymphocytes

    PubMed Central

    Shahani, Somayeh; Rostamnezhad, Mostafa; Ghaffari-rad, Vahid; Ghasemi, Arash; Allahverdi Pourfallah, Tayyeb

    2015-01-01

    The radioprotective effect of Achillea millefolium L (ACM) extract was investigated against genotoxicity induced by ionizing radiation (IR) in human lymphocytes. Peripheral blood samples were collected from human volunteers and incubated with the methanolic extract of ACM at different concentrations (10, 50, 100, and 200 μg/mL) for 2 hours. At each dose point, the whole blood was exposed in vitro to 2.5 Gy of X-ray and then the lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis-blocked binucleated cell. Antioxidant capacity of the extract was determined using free radical-scavenging method. The treatment of lymphocytes with the extract showed a significant decrease in the incidence of micronuclei binucleated cells, as compared with similarly irradiated lymphocytes without any extract treatment. The maximum protection and decrease in frequency of micronuclei were observed at 200 μg/mL of ACM extract which completely protected genotoxicity induced by IR in human lymphocytes. Achillea millefolium extract exhibited concentration-dependent radical-scavenging activity on 1,1-diphenyl-2-picryl hydrazyl free radicals. These data suggest that the methanolic extract of ACM may play an important role in the protection of normal tissues against genetic damage induced by IR. PMID:26675116

  10. The susceptibility of Campylobacter concisus to the bactericidal effects of normal human serum.

    PubMed

    Kirk, Karina Frahm; Nielsen, Hans Linde; Nielsen, Henrik

    2015-03-01

    Campylobacter concisus is an emerging pathogen of the gastrointestinal tract that has been associated with Barrett's oesophagus, enteritis and inflammatory bowel disease. Despite having invasive potential in intestinal epithelial cells in-vitro, bacteraemic cases with C. concisus are extremely scarce, having only been reported once. Therefore, we conducted a serum resistance assay to investigate the bactericidal effects of human complement on C. concisus in comparison to some other Campylobacter species. In total, 22 Campylobacter strains were tested by incubation with normal human serum and subsequent cultivation in microaerobic conditions for 48 hours. Killing time was evaluated by decrease in total CFU over time for incubation with different serum concentrations. Faecal isolates of C. concisus showed inoculum reduction to less than 50% after 30 min. Campylobacter jejuni was sensitive to serum, but killing was delayed and a bacteraemic Campylobacter fetus subsp. fetus isolate was completely serum resistant. Interestingly, sensitivity of enteric C. concisus to human serum was not associated to different faecal-calprotectin levels. We find that faecal isolates of C. concisus are sensitive to the bactericidal effects of serum, which may explain why C. concisus is not associated to bacteraemia.

  11. Trigeminal projections to thalamus and subthalamus in the hedgehog tenrec.

    PubMed

    Künzle, H

    1998-09-01

    The objective of the present study was the identification and characterization of the trigemino-diencephalic target areas in the Madagascan lesser hedgehog tenrec in order to get a more comprehensive view on the mammalian somatosensory thalamus, its evolution and representation in different species. Such an analysis has been considered important because in lower mammals the head and face are relatively well represented, but their ascending trigeminal projections have scarcely been analysed. Following injections of different tracer substances into the rostral and caudal portions of the trigeminal nuclear complex the most prominent area of termination was found in the medial ventroposterior nucleus. These projections were patchy and scarcely overlapped the region previously shown to receive spinal and dorsal column nuclear afferents. On the basis of the laterality and the intensity of the projections, two subdivisions were distinguished, the principal portion and the accessory portion receiving a dense contralateral and a weak bilateral input, respectively. They were considered equivalents to the magnocellular and parvocellular subdivisions of the medial ventroposterior nucleus in more differentiated mammals. In the latter species, however, the overlap between trigeminal and parabrachial fibres appears less extensive than in the tenrec. In addition, a weak bilateral projection was shown from the caudal trigeminal nucleus to the caudal and dorsal subdivision of the nucleus submedius. There was little, if any evidence for a trigeminal projection to the intralaminar nuclei and we failed to identify a correlate to the posterior nuclear complex of higher mammals. On the other hand, there was a distinct contralateral projection to the ventral portion of the zona incerta. This projection was of similar strength as the projection to the medial ventroposterior nucleus; it supports the notion that the zona incerta may play a crucial role in relaying trigeminal information.

  12. [A case of combined glossopharyngeal and trigeminal neuralgia].

    PubMed

    Katoh, Masahito; Aida, Toshimitsu; Moriwaki, Takuya; Yoshino, Masami; Aoki, Takeshi; Abumiya, Takeo; Imamura, Hiroyuki; Ogata, Akihiko

    2012-06-01

    It is well-known that idiopathic neuralgias of the trigeminal and glossopharyngeal nerves are caused by vascular compression at the root entry zone of the cranial nerves. Because they are functional diseases, initial treatment is medical, especially with carbamazepine. However, if medical therapy fails to adequately manage the pain, microvascular decompression (MVD) is prescribed. Glossopharyngeal neuralgia is rare, and combined trigeminal and glossopharyngeal neuralgia is an extremely rare disorder. A 70-year-old woman presented herself to Hokkaido Neurosurgical Memorial Hospital because of paroxysms of lancinating pain in her left pharynx and another lancinating pain in her left cheek. Carbamazepine, which was prescribed at another hospital, favorably relieved the pain; however, drug eruption compelled her to discontinue the medication. The multi-volume method revealed that a root entry zone of the left glossopharyngeal nerve was compressed by the left posterior inferior cerebellar artery, and the left trigeminal artery was compressed by the left superior cerebellar artery. MVD for both nerves was performed employing a left lateral suboccipital craniotomy. She experienced complete relief of pain immediately after MVD. Combined trigeminal and glossopharyngeal neuralgia is extremely rare, but some groups noted a relatively high incidence of concurrent trigeminal neuralgia in patients with glossopharyngeal neuralgia up until the 1970's. Glossopharyngeal neuralgia includes pain near the gonion; therefore, there is an overlap of symptoms between glossopharyngeal and trigeminal neuralgias. By virtue of recent progress in imaging technology, minute preoperative evaluations of microvascular compression are possible. Until the 1970's, there might have been some misunderstanding regarding the overlap of symptoms because of lack of the concept of microvascular compression as a cause of neuralgia and rudimentary imaging technology. Minute evaluations of both symptoms and

  13. Ecological Effect of Solithromycin on Normal Human Oropharyngeal and Intestinal Microbiota

    PubMed Central

    Rashid, Mamun-Ur; Rosenborg, Staffan; Panagiotidis, Georgios; Holm, Johan; Söderberg Löfdal, Karin; Nord, Carl Erik

    2016-01-01

    Solithromycin is a new fluoroketolide. The purpose of the present study was to investigate the effect of orally administered solithromycin on the human oropharyngeal and intestinal microbiota. Thirteen healthy volunteers (median age, 27.3 years) received oral solithromycin at 800 mg on day 1 followed by 400 mg daily on days 2 to 7. Fecal and saliva samples were collected at baseline and on days 2, 5, 7, 9, 14, and 21 for pharmacokinetic and microbiological analyses. Plasma samples were collected predose on days 2, 5, and 7 as proof of exposure, and solithromycin concentration ranges were 21.9 to 258 ng/ml, 18.0 to 386 ng/ml, and 16.9 to 417 ng/ml, respectively. The solithromycin concentrations in feces were 15.8 to 65.4 mg/kg, 24.5 to 82.7 mg/kg, 21.4 to 82.7 mg/kg, 12.1 to 72.4 mg/kg, 0.2 to 25.6 mg/kg, and 0 to 0.5 mg/kg on days 2, 5, 7, 9, 14, and 21, respectively. The numbers of enterobacteria and enterococci decreased and were normalized on day 14. The numbers of lactobacilli and bifidobacteria decreased from day 2 to day 14 and were normalized on day 21. The clostridia decreased on days 2, 7, and 14 and were normalized on day 21. No Clostridium difficile strains or toxins were detected during the study period. The number of Bacteroides strains was not significantly changed. The solithromycin concentrations in saliva were 0 to 1.2 mg/liter, 0 to 0.5 mg/liter, 0 to 0.5 mg/liter, and 0 to 0.1 mg/liter on days 2, 5, 7, and 9, respectively. The numbers of streptococci decreased on day 2 and were normalized on day 5. The numbers of lactobacilli, prevotellae, fusobacteria, and leptotrichiae decreased from day 2 and were normalized on day 21. PMID:27139483

  14. The anatomy of vascular compression in trigeminal neuralgia.

    PubMed

    Thomas, Krystin L; Vilensky, Joel A

    2014-01-01

    The etiological basis of trigeminal neuralgia (TN) is unknown but vascular (arterial and venous) compression of the trigeminal nerve roots has emerged as the likely cause in most cases. Here we examine the evidence for the "brain sagging/arterial elongation hypothesis" with reference to the cerebral arteries and veins believed to cause the compression. Most often implicated are the superior cerebellar artery, the anterior and posterior inferior cerebellar arteries, and the superior petrosal vein including several of its tributaries. The reviewed data suggest that the theoretical support for a vascular compressive etiology of TN is weak, albeit the surgical outcome data are relatively convincing.

  15. Trigeminal hypoplasia due to vertebrobasilar dolichoectasia: A new entity

    PubMed Central

    Jha, Abhishek; Gupta, Prakhar; Haroon, Mohammad; Shah, Gaurav; Gupta, Gagan; Khalid, Mohd.

    2015-01-01

    The term “vertebrobasilar dolichoectasia” refers to anomalous dilatation of the intracranial arteries associated with elongation or tortuosity of the affected vessels. The etiology of the disease is unknown and is usually detected incidentally. The predominant clinical manifestations arise due to the mass effect of the dilated vessels and may include cranial nerve compression, extrinsic aqueductal compression, motor and sensory disturbances. Trigeminal hypoplasia is a very uncommon condition, usually described in association with Goldenhar-Gorlin syndrome and has not yet been attributed to vertebrobasilar dolichoectasia. The current case report highlights this rare association of trigeminal nerve hypoplasia and vertebrobasilar dolichoectasia, leading to hemifacial and corneal anesthesia. PMID:26167222

  16. Normality and naturalness: a comparison of the meanings of concepts used within veterinary medicine and human medicine.

    PubMed

    Lerner, Henrik; Hofmann, Bjørn

    2011-12-01

    This article analyses the different connotations of "normality" and "being natural," bringing together the theoretical discussion from both human medicine and veterinary medicine. We show how the interpretations of the concepts in the different areas could be mutually fruitful. It appears that the conceptions of "natural" are more elaborate in veterinary medicine, and can be of value to human medicine. In particular they can nuance and correct conceptions of nature in human medicine that may be too idealistic. Correspondingly, the wide ranging conceptions of "normal" in human medicine may enrich conceptions in veterinary medicine, where the discussions seem to be sparse. We do not argue that conceptions from veterinary medicine should be used in human medicine and vice versa, but only that it could be done and that it may well be fruitful. Moreover, there are overlaps between some notions of normal and natural, and further conceptual analysis on this overlap is needed.

  17. Human-derived normal mesenchymal stem/stromal cells in anticancer therapies

    PubMed Central

    Zhang, Cheng; Yang, Shi-Jie; Wen, Qin; Zhong, Jiang F; Chen, Xue-Lian; Stucky, Andres; Press, Michael F; Zhang, Xi

    2017-01-01

    The tumor microenvironment (TME) not only plays a pivotal role during cancer progression and metastasis, but also has profound effects on therapeutic efficacy. Stromal cells of the TME are increasingly becoming a key consideration in the development of active anticancer therapeutics. However, dispute concerning the role of stromal cells to fight cancer continues because the use of mesenchymal stem/stromal cells (MSCs) as an anticancer agent is dependent on the specific MSCs subtype, in vitro or in vivo conditions, factors secreted by MSCs, types of cancer cell lines and interactions between MSCs, cancer cells and host immune cells. In this review, we mainly focus on the role of human-derived normal MSCs in anticancer therapies. We first discuss the use of different MSCs in the therapies for various cancers. We then focus on their anticancer mechanism and clinical application. PMID:28123601

  18. Chemical carcinogen-induced decreases in genomic 5-methyldeoxycytidine content of normal human bronchial epithelial cells

    SciTech Connect

    Wilson, V.L.; Smith, R.A.; Longoria, J.; Liotta, M.A.; Harper, C.M.; Harris, C.C.

    1987-05-01

    The genomic content of DNA 5-methyldeoxycytidine (m/sup 5/dC) was measured in dividing normal human bronchial epithelial cells treated with a broad range of chemical carcinogens. At noncytotoxic concentrations, all of the carcinogenic agents tested significantly reduced cellular DNA m/sup 5/dC content whereas the weakly carcinogenic and noncarcinogenic agents, benzo(e)pyrene and phenanthrene (respectively), did not. These reductions varied from 8% to 31% depending on the agent and the donor cells. The reduction is genomic m/sup 5/dC levels were concentration dependent for the carcinogenic polycyclic aromatic hydrocarbon benzo(a)pyrene. The authors speculate that carcinogen-induced perturbation of DNA m/sup 5/dC patterns may lead to heritable changes in gene expression and contribute to the molecular alterations involved in the initiation and the subsequent steps of the carcinogenesis process.

  19. Biochemical and metabolic abnormalities in normal and osteoarthritic human articular cartilage

    SciTech Connect

    Ryu, J.; Treadwell, B.V.; Mankin, H.J.

    1984-01-01

    Incorporation of radioactive precursors into macromolecules was studied with human normal and osteoarthritic articular cartilage organ culture. Analysis of the salt extracted matrix components separated by cesium chloride buoyant density gradient centrifugation showed an increase in the specific activities of all gradient fractions prepared from the osteoarthritic cartilage. Further analysis of these fractions showed the osteoarthritic cartilage contained 5 times as much sulfate incorporated into proteoglycans, and an even greater amount of 3H-glucosamine incorporated into material sedimenting to the middle of the gradient. Greater than half of this radioactive middle fraction appears to be hyaluronate, as judged by the position it elutes from a DEAE column and its susceptibility to hyaluronidase digestion. This study supports earlier findings showing increased rates of macromolecular synthesis in osteoarthritis, and in addition, an even greater synthetic rate for hyaluronic acid is demonstrated.

  20. Molecular basis for premature senescence induced by surfactants in normal human cells.

    PubMed

    Yamakami, Yoshimi; Miki, Kensuke; Yonekura, Ryuzo; Kudo, Ikuru; Fujii, Michihiko; Ayusawa, Dai

    2014-01-01

    Sublethal doses of surfactants as exemplified by NP-40 clearly induce premature senescence in normal human cells. To understand molecular basis for this phenomenon, we tried to suppress it with use of various inhibitors. An inhibitor of p38 of the MAPK family almost completely suppressed growth arrest and morphological changes induced by surfactants; however, other inhibitors tested had no effect. Oleic acid, a weak inducer of premature senescence, was found to suppress the effect of NP-40. Fluorescein-labeled oleic acid rapidly bound to the cell surface, and this binding was clearly blocked by pre-treatment with surfactants, suggesting that surfactants and oleic acid compete for binding to the cell surface. Moderate concentrations of cycloheximide, an inhibitor of protein synthesis, also suppressed the senescent features induced by NP-40. These results suggest that surfactants activate p38 signaling pathway by binding to the cell surface, and induce cellular senescence.

  1. Expression of the retinoblastoma protein is regulated in normal human tissues.

    PubMed Central

    Cordon-Cardo, C.; Richon, V. M.

    1994-01-01

    The nuclear phosphoprotein encoded by the retinoblastoma gene (pRB) appears to play a central role in control of cell division and differentiation. It is generally accepted that pRB is ubiquitously expressed. We investigated the expression of pRB in normal human tissues using immunochemical techniques to determine the expression of pRB in specific cell types. Maturing cells, both proliferating and nonproliferating, rather than their progenitors possess the highest levels of pRB. Cells of stratified epithelia, such as those from cervix, display strong immunostaining in the nondividing maturing suprabasal layer, whereas basal cells showed low to undetectable levels of pRB. Similar patterns of expression were observed in simple epithelia and hematopoietic cells contained within distinguishable proliferating compartments and in germ cell development. These studies are crucial to our understanding of processes involved in control of differentiation (tumorigenesis) as well as tumor progression. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8129035

  2. Normal Pressure Hydrocephalus in a Human Immunodeficiency Virus Type 1 Patient

    PubMed Central

    Regeti, Kalyani; Khan, Rafay; Jehangir, Waqas; Zafar, Shoaib; Yousif, Abdalla; Sen, Shuvendu

    2016-01-01

    Normal pressure hydrocephalus (NPH) is a relatively common disease of adulthood characterized by a typical combination of clinical and radiological findings. In this report, we discuss a 54-year-old female presenting with symptoms suggestive of NPH and found to have a history of human immunodeficiency virus (HIV) type 1. She was not treated as she was in denial state and developed NPH as a possible complication. In the literature, there has only been one reported case of HIV type 2 causing NPH; however, no relationship has been properly documented with HIV type 1. These findings bring about a question on whether NPH is associated or a complication of HIV with awareness of this association. Earlier screening of HIV can be done in patients presenting with such symptoms, thus to prevent further progression of its complications. PMID:27222676

  3. Effects of vasopressin administration on diuresis of water immersion in normal humans

    NASA Technical Reports Server (NTRS)

    Epstein, M.; Denunzio, A. G.; Loutzenhiser, R. D.

    1981-01-01

    The influence of vasopressin suppression on the diuresis encountered during water immersion is investigated in studies on normal humans immersed to the neck. Six hydrated male subjects were studied on two occasions while undergoing 6 h of immersion without or during the administration of aqueous vasopressin for the initial 4 h. Neck immersion is found to result in a significant increase in urinary flow rate beginning in the first hour and persisting throughout the immersion. The administration of vasopressin markedly attenuated the diuretic response throughout the period of infusion, while cessation of vasopressin administration during the final 2 h of immersion resulted in a marked offset of the antidiuresis. Results thus support the view that the suppression of antidiuretic hormone contributes to the immersion diuresis of hydrated subjects.

  4. Expression of MDR1 (multidrug resistance) gene and its protein in normal human kidney.

    PubMed

    Ernest, S; Rajaraman, S; Megyesi, J; Bello-Reuss, E N

    1997-01-01

    P-glycoprotein (Pgp), the product of the multidrug resistance (MDR) gene overexpressed in cancer cells, is present also in normal tissues. In the kidney, MDR1 Pgp has been found in the proximal tubule and in cultured mesangial cells. In situ hybridization and immunohistochemistry were used to determine the complete nephronal localization of MDR mRNA and its product, Pgp, in the human kidney. MDR mRNA expression was studied with the use of nonradioactive in situ MDR RNA probes. MDR1 Pgp was immunolocalized using the specific monoclonal antibody MRK16. The presence of MDR mRNA was confirmed in proximal tubules and mesangium, and demonstrated as well in thick limb of Henle's loops and in collecting ducts. MDR1 Pgp colocalized in the same nephronal segments. This suggests that, in addition to secreting xenobiotics, Pgp may play a role in the transport of endogenous substrates or in the regulation of Cl- channels.

  5. Immunolocalization of CYP1B1 in normal, human, fetal and adult eyes.

    PubMed

    Doshi, Manali; Marcus, Craig; Bejjani, Bassem A; Edward, Deepak P

    2006-01-01

    CYP1B1 is a cytochrome P450 enzyme implicated in autosomal recessive primary congenital glaucoma (PCG). The mechanism and function of CYP1B1 in the development of the PCG phenotype is unknown. Previously, investigators have reported detection of Cyp1b1 mRNA in the ciliary body and epithelium and neuroepithelium in the developing mouse eye, employing in situ hybridization techniques. Similarly, additional investigators have detected CYP1B1 mRNA in the iris, ciliary body, non-pigmented ciliary epithelial line, cornea, retinal-pigment epithelium, and retina in the human adult eye, using Northern blotting. This study was designed to immunolocalize CYP1B1 protein in the various ocular structures of normal, human fetal and adult eyes. Normal fetal and adult eyes were immunolabeled with a polyclonal antibody against human CYP1B1 using indirect immunofluorescence, and then compared with appropriate controls. The intensity of immunolabeling of the various ocular structures was assessed by qualitative and semi-quantitative techniques. In the anterior segment anti-CYP1B1 immunoreactivity (IR) was detected early in fetal development in the primitive ciliary epithelium. As well, the most intense CYP1B1 IR was in the non-pigmented ciliary epithelium. In addition, CYP1B1 IR was also present in the corneal epithelium and keratocytes, both layers of the iris pigmented epithelium, and retina. However, CYP1B1 IR was absent in the trabecular meshwork in all of the samples. In general, CYP1B1 immunolabeling in the human fetal eyes was more intense when compared to adult eyes. CYP1B1 IR was primarily immunolocalized to the non-pigmented ciliary epithelium and early in fetal development. In addition, CYP1B1 IR was not detected in the trabecular meshwork. These findings suggest that the abnormalities in the development of the trabecular meshwork in PCG may result from diminished or absent metabolism of important endogenous substrates in the ciliary epithelium due to non-functional CYP1B1

  6. Differential expression of imprinted genes in normal and IUGR human placentas.

    PubMed

    Diplas, Andreas I; Lambertini, Luca; Lee, Men-Jean; Sperling, Rhoda; Lee, Yin Leng; Wetmur, James; Chen, Jia

    2009-05-16

    Genomic imprinting refers to silencing of one parental allele in the zygotes of gametes depending upon the parent of origin. Loss of imprinting (LOI) is the gain of function from the silent allele that can have a maximum effect of doubling the gene dosage. LOI may play a significant role in the etiology of intrauterine growth restriction (IUGR). Using placental tissue from ten normal and seven IUGR pregnancies, we conducted a systematic survey of the expression of a panel of 74 "putatively" imprinted genes using quantitative RT-PCR. We found that 52/74 ( approximately 70%) of the genes were expressed in human placentas. Nine of the 52 (17%) expressed genes were significantly differentially expressed between normal and IUGR placentas; five were upregulated (PHLDA2, ILK2, NNAT, CCDC86, PEG10) and four downregulated (PLAGL1, DHCR24, ZNF331, CDKAL1). We also assessed LOI profile of 14 imprinted genes in 14 normal and 24 IUGR placentas using a functional and sensitive assay developed in our laboratory. Little LOI was observed in any placentas for five of the genes (PEG10, PHLDA2, MEG3, EPS15, CD44). With the 149 heterozygosities examined, 40 (26.8%) exhibited LOI >3%. Some genes exhibited frequent LOI in placentas regardless of the disease status (IGF2, TP73, MEST, SLC22A18, PEG3), while others exhibited LOI only in IUGR placentas (PLAGL1, DLK1, H19, SNRPN). Importantly, there was no correlation between gene expression and LOI profile. Our study suggests that genomic imprinting may play a role in IUGR pathogenesis, but mechanisms other than LOI may contribute to dysregulation of imprinted genes.

  7. Normal and cancer stem cells of the human female reproductive system

    PubMed Central

    2013-01-01

    The female reproductive system (FRS) has a great capacity for regeneration. The existence of somatic stem cells (SSC) that are likely to reside in distinct tissue compartments of the FRS is anticipated. Normal SSC are capable of regenerating themselves, produce a progeny of cells that differentiate and maintain tissue architecture and functional characteristics, and respond to homeostatic controls. Among those SSC of the FRS that have been identified are: a) undifferentiated cells capable of differentiating into thecal cells and synthesizing hormones upon transplantation, b) ovarian surface epithelium stem cells, mitotically responsive to ovulation, c) uterine endometrial and myometrial cells, as clonogenic epithelial and stromal cells, and d) epithelial and mesenchymal cells with self-renewal capacity and multipotential from cervical tissues. Importantly, these cells are believed to significantly contribute to the development of different pathologies and tumors of the FRS. It is now widely accepted that cancer stem cells (CSC) are at the origin of many tumors. They are capable of regenerating themselves, produce a progeny that will differentiate aberrantly and do not respond adequately to homeostatic controls. Several cell surface antigens such as CD44, CD117, CD133 and MYD88 have been used to isolate ovarian cancer stem cells. Clonogenic epithelial and stromal endometrial and myometrial cells have been found in normal and cancer tissues, as side population, label-retaining cells, and CD146/PDGF-R beta-positive cells with stem-like features. In summary, here we describe a number of studies supporting the existence of somatic stem cells in the normal tissues and cancer stem cells in tumors of the human female reproductive system. PMID:23782518

  8. Melanogenesis and antioxidant defense system in normal human melanocytes cultured in the presence of chlorpromazine.

    PubMed

    Otreba, Michał; Wrześniok, Dorota; Beberok, Artur; Rok, Jakub; Buszman, Ewa

    2015-02-01

    Chlorpromazine is used in the treatment of schizophrenia and psychotic disorders and belongs to phenothiazine class of neuroleptic drugs. It shows severe side effects such as extrapyramidal symptoms as well as ocular and skin disorders, but the mechanism is still not fully established. The aim of this study was to examine the effect of chlorpromazine on cell viability, melanogenesis and antioxidant defense system in normal human melanocytes. It has been demonstrated that chlorpromazine induces concentration dependent loss in cell viability. The value of EC(50) was calculated to be 2.53 μM. Chlorpromazine in lower concentrations (0.0001, 0.001 and 0.01 μM) increased the melanin and microphthalmia-associated transcription factor (MITF) content and tyrosinase activity, while changes of antioxidant enzymes activity were not observed. It suggests that long-term chlorpromazine therapy, even with low drug doses, may lead to hyperpigmentation disorders in skin and/or eye. The use of the analyzed drug in higher concentrations (0.1 and 1.0 μM) caused significant alterations of antioxidant enzymes activity in normal melanocytes, what may explain a potential role of chlorpromazine in the depletion of cellular antioxidant status leading to other adverse effects associated with the high-dose and/or long-term therapy.

  9. Binding of normal human IgG to myelin sheaths, glia and neurons.

    PubMed Central

    Aarli, J A; Aparicio, S R; Lumsden, C E; Tönder, O

    1975-01-01

    The binding of normal human serum, purified IgG and IgG fragments to central nervous tissue was studied by the anti-globulin consumption (AGCT) and immunofluorescence (IF) techniques. In the AGCT, F(ab')2 fragments failed to react, whereas IgG and Fc fragments did so. In IF experiments, the binding was localized to myelin sheaths, glia and neurons; Fab monomers at a protein concentration of 1-3 mg/ml dod not react with the tissue, but purified Fc fragments at 0-0625 mg/ml did. The binding is neither tissue- nor species-specific. Lipid and protein extraction procedures indicated that the factor responsible for binding to myelin was basic protein. It was concluded that the binding of normal IgG to central nervous tissue is medicated by the Fc part of the molecule. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 PMID:803915

  10. Optical redox imaging indices discriminate human breast cancer from normal tissues

    NASA Astrophysics Data System (ADS)

    Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

    2016-11-01

    Our long-term goal was to investigate the potential of incorporating redox imaging technique as a breast cancer (BC) diagnosis component to increase the positive predictive value of suspicious imaging finding and to reduce unnecessary biopsies and overdiagnosis. We previously found that precancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. We also revealed abnormal mitochondrial redox state in cancerous specimens from three BC patients. Here, we extend our study to include biopsies of 16 patients. Tissue aliquots were collected from both apparently normal and cancerous tissues from the affected cancer-bearing breasts shortly after surgical resection. All specimens were snap-frozen and scanned with the Chance redox scanner, i.e., the three-dimensional cryogenic NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins) fluorescence imager. We found both Fp and NADH in the cancerous tissues roughly tripled that in the normal tissues (p<0.05). The redox ratio Fp/(NADH + Fp) was ˜27% higher in the cancerous tissues (p<0.05). Additionally, Fp, or NADH, or the redox ratio alone could predict cancer with reasonable sensitivity and specificity. Our findings suggest that the optical redox imaging technique can provide parameters independent of clinical factors for discriminating cancer from noncancer breast tissues in human patients.

  11. Characterization of human normal and cancerous gastric submucosa based on multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Zhong, Jiazhao; Chen, G.; Liu, Y. C.; Zhuo, S. M.; Chen, J. X.; Yan, J.

    2012-03-01

    Gastric cancer is one of the most frequent cancers in the world; almost two-thirds of gastric cancer cases and deaths occur in less developed regions. The initial diagnosis of gastric cancer often is delayed because up to 80 percent of patients are asymptomatic during the early stages of stomach cancer. So the ability to perform real-time in vivo histological diagnosis for early gastric cancer at the cellular level during ongoing endoscopy is a long-standing goal of endoscopists. In this paper, using multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG), MPM images of human normal and cancerous gastric submucosa were obtained at excitation wavelength of 800 nm. The features such as the appearance of abnormal cells and the large loss of collagen in cancerous gastric submucosa were extracted to be as significant indicators to distinguish cancerous submucosa from normal submucosa. With the implementation of multiphoton microscopy concept in endoscopy applications, multiphoton endoscopy might realize in vivo histological diagnosis goal of endoscopists.

  12. Characterization of human normal and cancerous gastric submucosa based on multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Zhong, Jiazhao; Chen, G.; Liu, Y. C.; Zhuo, S. M.; Chen, J. X.; Yan, J.

    2011-11-01

    Gastric cancer is one of the most frequent cancers in the world; almost two-thirds of gastric cancer cases and deaths occur in less developed regions. The initial diagnosis of gastric cancer often is delayed because up to 80 percent of patients are asymptomatic during the early stages of stomach cancer. So the ability to perform real-time in vivo histological diagnosis for early gastric cancer at the cellular level during ongoing endoscopy is a long-standing goal of endoscopists. In this paper, using multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG), MPM images of human normal and cancerous gastric submucosa were obtained at excitation wavelength of 800 nm. The features such as the appearance of abnormal cells and the large loss of collagen in cancerous gastric submucosa were extracted to be as significant indicators to distinguish cancerous submucosa from normal submucosa. With the implementation of multiphoton microscopy concept in endoscopy applications, multiphoton endoscopy might realize in vivo histological diagnosis goal of endoscopists.

  13. RNA expression profile of calcified bicuspid, tricuspid, and normal human aortic valves by RNA sequencing.

    PubMed

    Guauque-Olarte, Sandra; Droit, Arnaud; Tremblay-Marchand, Joël; Gaudreault, Nathalie; Kalavrouziotis, Dimitri; Dagenais, Francois; Seidman, Jonathan G; Body, Simon C; Pibarot, Philippe; Mathieu, Patrick; Bossé, Yohan

    2016-10-01

    The molecular mechanisms leading to premature development of aortic valve stenosis (AS) in individuals with a bicuspid aortic valve are unknown. The objective of this study was to identify genes differentially expressed between calcified bicuspid aortic valves (BAVc) and tricuspid valves with (TAVc) and without (TAVn) AS using RNA sequencing (RNA-Seq). We collected 10 human BAVc and nine TAVc from men who underwent primary aortic valve replacement. Eight TAVn were obtained from men who underwent heart transplantation. mRNA levels were measured by RNA-Seq and compared between valve groups. Two genes were upregulated, and none were downregulated in BAVc compared with TAVc, suggesting a similar gene expression response to AS in individuals with bicuspid and tricuspid valves. There were 462 genes upregulated and 282 downregulated in BAVc compared with TAVn. In TAVc compared with TAVn, 329 genes were up- and 170 were downregulated. A total of 273 upregulated and 147 downregulated genes were concordantly altered between BAVc vs. TAVn and TAVc vs. TAVn, which represent 56 and 84% of significant genes in the first and second comparisons, respectively. This indicates that extra genes and pathways were altered in BAVc. Shared pathways between calcified (BAVc and TAVc) and normal (TAVn) aortic valves were also more extensively altered in BAVc. The top pathway enriched for genes differentially expressed in calcified compared with normal valves was fibrosis, which support the remodeling process as a therapeutic target. These findings are relevant to understand the molecular basis of AS in patients with bicuspid and tricuspid valves.

  14. Se status in normal and pathological human individuals before and after Se supplementation

    NASA Astrophysics Data System (ADS)

    Bellisola, G.; Cinque, G.; Galassini, S.; Guidi, G. C.; Liu, N. Q.; Moschini, G.

    1996-04-01

    The determination of selenium in plasma and in urine samples has been suggested for the assessment of Se status in human individuals. The kidney is of fundamental importance in Se homeostasis: with low Se intake its excretion will be decreased and with high Se intake it will be increased. In 21 patients with kidney disease (8 with normal kidney function and 13 with moderate renal failure) Se was measured in 1 ml of urine by PIXE after preconcentration of the sample. The total urine volume was measured to calculate total daily Se excretion. The same procedure was applied to 14 normal individuals for comparison. All individuals were then supplemented orally with selenite for 8 weeks (Se = 600 μg/day) and the procedure was repeated. The behaviour of the major selenoproteins was also investigated by measuring glutathione peroxidase activities in plasma, in platelets and in erythrocyte samples. For renal function, serum and urine creatinine concentrations were utilised and creatinine clearances were calculated. Results obtained were compared before and after Se treatment and between groups. Some correlation studies were carried out between Se and kidney functions and/or selenoperoxidase activities.

  15. Surface modification of microparticles causes differential uptake responses in normal and tumoral human breast epithelial cells

    PubMed Central

    Patiño, Tania; Soriano, Jorge; Barrios, Lleonard; Ibáñez, Elena; Nogués, Carme

    2015-01-01

    The use of micro- and nanodevices as multifunctional systems for biomedical applications has experienced an exponential growth during the past decades. Although a large number of studies have focused on the design and fabrication of new micro- and nanosystems capable of developing multiple functions, a deeper understanding of their interaction with cells is required. In the present study, we evaluated the effect of different microparticle surfaces on their interaction with normal and tumoral human breast epithelial cell lines. For this, AlexaFluor488 IgG functionalized polystyrene microparticles (3 μm) were coated with Polyethyleneimine (PEI) at two different molecular weights, 25 and 750 kDa. The effect of microparticle surface properties on cytotoxicity, cellular uptake and endocytic pathways were assessed for both normal and tumoral cell lines. Results showed a differential response between the two cell lines regarding uptake efficiency and mechanisms of endocytosis, highlighting the potential role of microparticle surface tunning for specific cell targeting. PMID:26068810

  16. Protective effects of catalase overexpression on UVB-induced apoptosis in normal human keratinocytes.

    PubMed

    Rezvani, Hamid Reza; Mazurier, Frédéric; Cario-André, Muriel; Pain, Catherine; Ged, Cécile; Taïeb, Alain; de Verneuil, Hubert

    2006-06-30

    UV-induced apoptosis in keratinocytes is a highly complex process in which various molecular pathways are involved. These include the extrinsic pathway via triggering of death receptors and the intrinsic pathway via DNA damage and reactive oxygen species (ROS) formation. In this study we investigated the effect of catalase and CuZn-superoxide dismutase (SOD) overexpression on apoptosis induced by UVB exposure at room temperature or 4 degrees C on normal human keratinocytes. Irradiation at low temperature reduced UV-induced apoptosis by 40% in normal keratinocytes independently of any change in p53 and with a decrease in caspase-8 activation. Catalase overexpression decreased apoptosis by 40% with a reduction of caspase-9 activation accompanied by a decrease in p53. Keeping cells at low temperature and catalase overexpression had additive effects. CuZn-SOD overexpression had no significant effect on UVB-induced apoptosis. UVB induced an increase in ROS levels at two distinct stages: immediately following irradiation and around 3 h after irradiation. Catalase overexpression inhibited only the late increase in ROS levels. We conclude that catalase overexpression has a protective role against UVB irradiation by preventing DNA damage mediated by the late ROS increase.

  17. Novel CT-guided biopsy of isolated perineural spread of adenoid cystic carcinoma along the trigeminal nerve masquerading as chronic trigeminal neuropathy.

    PubMed

    Yong, Xian Zhang Eric; Dillon, Jonathan; Smith, Paul; Salinas-La Rosa, Cesar; Jhamb, Ashu

    2017-02-01

    The differential diagnoses for chronic peripheral neuropathy are broad and diagnosing a cause can be challenging. We present a case of isolated perineural spread of adenoid cystic carcinoma to the trigeminal nerve involving skull base foramina and Meckel's cave in the setting of chronic trigeminal neuropathy and no known prior malignancy. Computed tomography-guided core (CT) needle biopsy was needed to arrive at a diagnosis and a novel approach was required to obtain tissue from the trigeminal nerve lesion at foramen ovale.

  18. Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology

    PubMed Central

    Raffensperger, Zachary D.; Heike, Carrie L.; Cunningham, Michael L.; Hecht, Jacqueline T.; Kau, Chung How; Moreno, Lina M.; Wehby, George L.; Murray, Jeffrey C.; Laurie, Cecelia A.; Laurie, Cathy C.; Santorico, Stephanie; Klein, Ophir; Feingold, Eleanor; Hallgrimsson, Benedikt; Spritz, Richard A.; Marazita, Mary L.; Weinberg, Seth M.

    2016-01-01

    Numerous lines of evidence point to a genetic basis for facial morphology in humans, yet little is known about how specific genetic variants relate to the phenotypic expression of many common facial features. We conducted genome-wide association meta-analyses of 20 quantitative facial measurements derived from the 3D surface images of 3118 healthy individuals of European ancestry belonging to two US cohorts. Analyses were performed on just under one million genotyped SNPs (Illumina OmniExpress+Exome v1.2 array) imputed to the 1000 Genomes reference panel (Phase 3). We observed genome-wide significant associations (p < 5 x 10−8) for cranial base width at 14q21.1 and 20q12, intercanthal width at 1p13.3 and Xq13.2, nasal width at 20p11.22, nasal ala length at 14q11.2, and upper facial depth at 11q22.1. Several genes in the associated regions are known to play roles in craniofacial development or in syndromes affecting the face: MAFB, PAX9, MIPOL1, ALX3, HDAC8, and PAX1. We also tested genotype-phenotype associations reported in two previous genome-wide studies and found evidence of replication for nasal ala length and SNPs in CACNA2D3 and PRDM16. These results provide further evidence that common variants in regions harboring genes of known craniofacial function contribute to normal variation in human facial features. Improved understanding of the genes associated with facial morphology in healthy individuals can provide insights into the pathways and mechanisms controlling normal and abnormal facial morphogenesis. PMID:27560520

  19. Ciliogenesis in normal human kidney development and post-natal life.

    PubMed

    Saraga-Babić, Mirna; Vukojević, Katarina; Bočina, Ivana; Drnašin, Kristina; Saraga, Marijan

    2012-01-01

    Ciliogenesis in developing and post-natal human kidneys appears to influence cell proliferation and differentiation, apico-basal cell polarity, and tubular lumen formation. We have analyzed the appearance of primary cilia and differentiation of kidney cells in ten human conceptuses aged 6-22 weeks and in one 5-year-old kidney, using a double immunofluorescence labeling technique for α-tubulin, γ-tubulin, Oct-4, and Ki-67 and by electron microscopy. Immature forms of nephrons and ampullae were characterized by intense cell proliferation, which subsequently decreased during development. Primary cilia appeared on the surfaces of non-proliferating cells in developing nephrons, gradually increasing in length from 0.59 μm in renal vesicles to 0.81 μm in the S-forms of nephrons, ultimately reaching 3.04 μm in length in mature fetal and post-natal nephrons. Ciliary length increased from 0.59 μm in ampullae to 1.28 μm in post-natal collecting tubules. Mesenchymal to epithelial transformation of kidney cells coincided with the appearance of apico-basal polarity, both gap and tight junctions, and lumen formation. Up-regulation of Oct-4 expression correlated with the onset of kidney cell differentiation. Our results demonstrate the importance of proper primary cilia lengthening and Oct-4 expression for the normal development of fetal and post-natal kidneys and of apico-basal polarity for normal tubular lumen formation. Disturbances in these processes are associated with ciliopathies.

  20. Low Density Lipoprotein and Non-Newtonian Oscillating Flow Biomechanical Parameters for Normal Human Aorta

    PubMed Central

    Soulis, Johannes V.; Fytanidis, Dimitrios K.; Lampri, Olga P.; Giannoglou, George D.

    2016-01-01

    Background The temporal variation of the hemodynamic mechanical parameters during cardiac pulse wave is considered as an important atherogenic factor. Applying non-Newtonian blood molecular viscosity simulation is crucial for hemodynamic analysis. Understanding low density lipoprotein (LDL) distribution in relation to flow parameters will possibly spot the prone to atherosclerosis aorta regions. Methods The biomechanical parameters tested were averaged wall shear stress (AWSS), oscillatory shear index (OSI) and relative residence time (RRT) in relation to the LDL concentration. Four non-Newtonian molecular viscosity models and the Newtonian one were tested for the normal human aorta under oscillating flow. The analysis was performed via computational fluid dynamic. Results Tested viscosity blood flow models for the biomechanical parameters yield a consistent aorta pattern. High OSI and low AWSS develop at the concave aorta regions. This is most noticeable in downstream flow region of the left subclavian artery and at concave ascending aorta. Concave aorta regions exhibit high RRT and elevated LDL. For the concave aorta site, the peak LDL value is 35.0% higher than its entrance value. For the convex site, it is 18.0%. High LDL endothelium regions located at the aorta concave site are well predicted with high RRT. Conclusions We are in favor of using the non-Newtonian power law model for analysis. It satisfactorily approximates the molecular viscosity, WSS, OSI, RRT and LDL distribution. Concave regions are mostly prone to atherosclerosis. The flow biomechanical factor RRT is a relatively useful tool for identifying the localization of the atheromatic plaques of the normal human aorta. PMID:28197271

  1. Cytosolic dsDNA triggers apoptosis and pro-inflammatory cytokine production in normal human melanocytes.

    PubMed

    Wang, Suiquan; Liu, Dongyin; Ning, Weixuan; Xu, Aie

    2015-04-01

    Considerable evidence implicates that viral infection might be a participant factor in the pathogenesis of vitiligo. However, it is still unclear how viral infection leads to the melanocyte destruction. To elucidate the effects of viral dsDNA on the viability and cytokine synthesis of normal human melanocytes and to explore the underlying mechanisms, primary cultured normal human melanocytes were transfected with poly(dA:dT). The results demonstrated that poly(dA:dT) triggered apoptosis instead of pyroptosis in melanocytes. Knocking down AIM2 or RIG-I by RNA interference partially reduced the poly(dA:dT)-induced LDH release, suggesting the involvement of both nucleic acid sensors in the process of melanocyte death. Poly(dA:dT) induced the expression of pro-inflammatory cytokine genes including IFN-β, TNF-α, IL-6 and IL-8 as well, whereas the pro-inflammatory cytokine production was suppressed by RIG-I siRNA, but not by AIM2 siRNA. Poly(dA:dT) treatment increased the phosphorylation of p38 and JNK and NFκB. Accordingly, NFκB inhibitor Bay 11-7082 and JNK inhibitor SP600125 blocked the induction of the cytokine genes except IFN-β. The production of IL6 and IL8 was also suppressed by p38 inhibitor SB203580. On the contrary, the Poly(dA:dT)-induced melanocyte death was only decreased by SP600125. This study provides the possible mechanism of melanocyte destruction and immuno-stimulation in vitiligo by innate immune response following viral infection.

  2. Posttranslational N-glycosylation takes place during the normal processing of human coagulation factor VII.

    PubMed

    Bolt, Gert; Kristensen, Claus; Steenstrup, Thomas Dock

    2005-05-01

    N-glycosylation is normally a cotranslational process that occurs during translocation of the nascent protein to the endoplasmic reticulum. In the present study, however, we demonstrate posttranslational N-glycosylation of recombinant human coagulation factor VII (FVII) in CHO-K1 and 293A cells. Human FVII has two N-glycosylation sites (N145 and N322). Pulse-chase labeled intracellular FVII migrated as two bands corresponding to FVII with one and two N-glycans, respectively. N-glycosidase treatment converted both of these band into a single band, which comigrated with mutated FVII without N-glycans. Immediately after pulse, most labeled intracellular FVII had one N-glycan, but during a 1-h chase, the vast majority was processed into FVII with two N-glycans, demonstrating posttranslational N-glycosylation of FVII. Pulse-chase analysis of N-glycosylation site knockout mutants demonstrated cotranslational glycosylation of N145 but primarily or exclusively posttranslational glycosylation of N322. The posttranslational N-glycosylation appeared to take place in the same time frame as the folding of nascent FVII into a secretion-competent conformation, indicating a link between the two processes. We propose that the cotranslational conformation(s) of FVII are unfavorable for glycosylation at N332, whereas a more favorable conformation is obtained during the posttranslational folding. This is the first documentation of posttranslational N-glycosylation of a non-modified protein in mammalian cells with an intact N-glycosylation machinery. Thus, the present study demonstrates that posttranslational N-glycosylation can be a part of the normal processing of glycoproteins.

  3. Activation properties of trigeminal motoneurons in participants with and without bruxism

    PubMed Central

    D'Amico, Jessica M.; Yavuz, Ş. Utku; Saraçoğlu, Ahmet; Atiş, Elif Sibel; Türker, Kemal S.

    2013-01-01

    In animals, sodium- and calcium-mediated persistent inward currents (PICs), which produce long-lasting periods of depolarization under conditions of low synaptic drive, can be activated in trigeminal motoneurons following the application of the monoamine serotonin. Here we examined if PICs are activated in human trigeminal motoneurons during voluntary contractions and under physiological levels of monoaminergic drive (e.g., serotonin and norepinephrine) using a paired motor unit analysis technique. We also examined if PICs activated during voluntary contractions are larger in participants who demonstrate involuntary chewing during sleep (bruxism), which is accompanied by periods of high monoaminergic drive. In control participants, during a slowly increasing and then decreasing isometric contraction, the firing rate of an earlier-recruited masseter motor unit, which served as a measure of synaptic input to a later-recruited test unit, was consistently lower during derecruitment of the test unit compared with at recruitment (ΔF = 4.6 ± 1.5 imp/s). The ΔF, therefore, is a measure of the reduction in synaptic input needed to counteract the depolarization from the PIC to provide an indirect estimate of PIC amplitude. The range of ΔF values measured in the bruxer participants during similar voluntary contractions was the same as in controls, suggesting that abnormally high levels of monoaminergic drive are not continually present in the absence of involuntary motor activity. We also observed a consistent “onion skin effect” during the moderately sized contractions (<20% of maximal), whereby the firing rate of higher threshold motor units discharged at slower rates (by 4–7 imp/s) compared with motor units with relatively lower thresholds. The presence of lower firing rates in the more fatigue-prone, higher threshold trigeminal motoneurons, in addition to the activation of PICs, likely facilitates the activation of the masseter muscle during motor activities

  4. Differential effects of NGF and NT-3 on embryonic trigeminal axon growth patterns.

    PubMed

    Ulupinar, E; Jacquin, M F; Erzurumlu, R S

    2000-09-18

    We examined the effects of neurotrophins nerve growth factor (NGF) and neurotrophin-3 (NT-3) on trigeminal axon growth patterns. Embryonic (E13-15) wholemount explants of the rat trigeminal pathway including the whisker pads, trigeminal ganglia, and brainstem were cultured in serum-free medium (SFM) or SFM supplemented with NGF or NT-3 for 3 days. Trigeminal axon growth patterns were analyzed with the use of lipophilic tracer DiI. In wholemount cultures grown in SFM, trigeminal axon projections, growth patterns, and differentiation of peripheral and central targets are similar to in vivo conditions. We show that in the presence of NGF, central trigeminal axons leave the tract and grow into the surrounding brainstem regions in the elongation phase without any branching. On the other hand, NT-3 promotes precocious development of short axon collaterals endowed with focal arbors along the sides of the central trigeminal tract. These neurotrophins also affect trigeminal axon growth within the whisker pad. Additionally, we cultured dissociated trigeminal ganglion cells in the presence of NGF, NT-3, or NGF+NT-3. The number of trigeminal ganglion cells, their size distribution under each condition were charted, and axon growth was analyzed following immunohistochemical labeling with TrkA and parvalbumin antibodies. In these cultures too, NGF led to axon elongation and NT-3 to axon arborization. Our in vitro analyses suggest that aside from their survival promoting effects, NGF and NT-3 can differentially influence axon growth patterns of embryonic trigeminal neurons.

  5. Metabolism of aflatoxin B1 by normal human bronchial epithelial cells.

    PubMed

    Van Vleet, T R; Klein, P J; Coulombe, R A

    2001-08-10

    Aflatoxin B, (AFB1) is a potent hepatocarcinogen in animal models and a suspected carcinogen in humans. High concentrations of AFB, have been found in respirable grain dusts, and may therefore be a risk factor for human lung cancer in certain occupations. To study the potential for AFB, activation in human lung, cytochrome P-450 (CYP)-mediated activation and glutathione S-transferase (GST)-mediated detoxification of AFB1 were examined in cultured normal human bronchial epithelial (NHBE) cells. Cells were exposed to 0. 15 microM or 1.5 microM AFB, for 48 h and media was collected for metabolite analysis by high-performance liquid chromatography (HPLC). At 0. 15 microM, AFB1 was metabolized only to the detoxified metabolite aflatoxin Q1 (AFQ1). At 1.5 microM AFB1, both aflatoxin M1 (AFM1), and AFQ1 were produced. Cells pretreated with 50 degrees M 3-methylcholanthrene (3MC), a CYP 1A inducer, for 72 h prior to 0.15 microM AFB1, produced the activated AFB1 8,9-epoxide (AFBO). Similarly, microsomes prepared from 3MC-pretreated cells formed AFBO, but microsomes from noninduced cells did not. While AFB1-DNA adducts were not detected at low AFB1 concentrations in untreated NHBE, 3MC induction caused the production of AFB1-DNA adducts at 0.015 and 0.15 microM AFB1. Western immunoblots showed that the primary CYP isoforms responsible for AFB1 activation in the liver, 1A and 3A4, to be constitutively expressed in NHBE cells. Expression of CYP 1A was significantly increased in 3MC-pretreated cells, while CYP 3A4 expression increased slightly, but not to the extent of the 1A isoforms. The principal AFBO detoxifying enzyme, glutathione S-transferase (GST), was constitutively expressed in NHBE cells, and was increased approximately twofold by 3MC pretreatment. Cytosolic fractions from neither control nor 3MC-induced NHBE had measurable AFBO conjugating activity, indicating that these cells may lack AFB1-relevant GST activity. From these data, it appears that NHBE cells activate

  6. Meeting research needs with postmortem biospecimen donation: summary of recommendations for postmortem recovery of normal human biospecimens for research.

    PubMed

    Mucci, Neil R; Moore, Helen M; Brigham, Lori E; Goldthwaite, Charles A; Little, A Roger; Lockhart, Nicole C; Scott, Michael P; Struewing, Jeffery P; Vincent, Stephen L; Compton, Carolyn C

    2013-04-01

    Normal human tissues, bodily fluids, and other biospecimens of known quality are essential for research to understand the development of cancer and other diseases and to develop new diagnostics and therapies. However, obtaining normal biospecimens appropriate for contemporary large-scale molecular and genomic research is one of the most challenging biospecimen acquisition problems for scientists and biospecimen resources that support research. Recognizing this challenge, the U.S. National Cancer Institute recently convened a series of workshops and meetings focused on the acquisition of normal tissues for research and produced an extensive document, Recommendations for Postmortem Recovery of Normal Human Biospecimens for Research. This article summarizes these recommendations, addressing key ethical, operational, and scientific elements for collecting normal reference biospecimens from postmortem donors in the U.S. Awareness of these recommendations can foster more effective collaborations and mitigate potential logistical challenges, while promoting postmortem biospecimen donation options for families and increasing the availability of high quality normal biospecimens for research. The recommendations have been put into practice in the collection of normal human biospecimens for the NIH Genotype-Tissue Expression Program (GTEx), a pilot study of human gene expression and regulation in multiple tissues which will provide valuable insights into the mechanisms of gene regulation and, in the future, its disease-related perturbations (http://commonfund.nih.gov/GTEx/).

  7. Higher Leptin but Not Human Milk Macronutrient Concentration Distinguishes Normal-Weight from Obese Mothers at 1-Month Postpartum

    PubMed Central

    Frasquet-Darrieux, Marine; Gaud, Marie-Agnès; Christin, Patricia; Boquien, Clair-Yves; Millet, Christine; Herviou, Manon; Darmaun, Dominique; Robins, Richard J.; Ingrand, Pierre; Hankard, Régis

    2016-01-01

    Introduction Exclusively breastfed infants born to obese mothers have previously been shown to gain less weight by 1-month postpartum than infants of normal-weight mothers. Our hypothesis is that human milk composition and volume may differ between obese and normal-weight mothers. Objective To compare human milk leptin, macronutrient concentration, and volume in obese and normal-weight mothers. Mother and infant characteristics were studied as secondary aims. Materials and Methods This cross-sectional observational study compared 50 obese mothers matched for age, parity, ethnic origin, and educational level with 50 normal-weight mothers. Leptin, macronutrient human milk concentration, and milk volume were determined at 1 month in exclusively breastfed infants. Mother characteristics and infant growth were recorded. Results Human milk leptin concentration was higher in obese mothers than normal-weight mothers (4.8±2.7 vs. 2.5±1.5 ng.mL-1, p<0.001). No difference was observed between obese and normal-weight mothers in protein, lipid, carbohydrate content, and volume, nor in infant weight gain. Conclusion Leptin concentration was higher in the milk of obese mothers than that of normal-weight mothers, but macronutrient concentration was not. It remains to be established whether the higher leptin content impacts on infant growth beyond the 1-month of the study period. PMID:28005966

  8. Plasma fibronectin synthesis in normal and injured humans as determined by stable isotope incorporation.

    PubMed Central

    Thompson, C; Blumenstock, F A; Saba, T M; Feustel, P J; Kaplan, J E; Fortune, J B; Hough, L; Gray, V

    1989-01-01

    In humans, plasma fibronectin decreases early after operative injury, burn, or trauma, followed by a rapid restoration with a secondary decline typically observed if such patients become septic. We determined the rate of plasma fibronectin and plasma fibrinogen synthesis in normal subjects and injured patients using a stable isotope incorporation technique with [15N]glycine. During a constant 14-h infusion of [15N]glycine, the enrichment of [15N]glycine in both the free plasma glycine precursor pool as well as the urinary hippurate pool was determined; the latter used as an estimate of intracellular hepatic precursor enrichment. [15N]Glycine enrichment in both plasma fibronectin and fibrinogen was also quantified. The synthesis rate (Js/V) expressed in micrograms per milliliter of plasma per hour and the fractional synthesis rate (FSR) expressed as percentage of the plasma pool produced per day were determined. In normal subjects, the FSR for plasma fibronectin using 15N enrichment into urinary hippurate was 35.35 +/- 1.46%/d, whereas the Js/V was 4.45 +/- 0.19 micrograms/ml plasma per h. In normal subjects, the FSR for plasma fibronectin using 15N enrichment into free plasma glycine was 14.73 +/- 0.63%/d, whereas the Js/V was 1.98 +/- 0.09 micrograms/ml plasma per h. Early (2-3 d) after burn injury, fibronectin synthesis was increased (Js/V = 5.74 +/- 0.36; P less than 0.05), whereas later after injury, fibronectin synthesis began to decline (Js/V = 3.52 +/- 0.24; P less than 0.05) based on 15N enrichment of urinary hippurate. In contrast, the Js/V and FSR of plasma fibrinogen, a well-documented acute-phase plasma protein, revealed a sustained elevation (P less than 0.05) after injury in both the trauma and burn patients. Thus, plasma fibronectin synthesis is elevated early postinjury, which may contribute to the rapid restoration of its blood level. However, once fibronectin levels have normalized, the synthesis of plasma fibronectin appears to decline. PMID

  9. Acute effect of inhaled bradykinin on tracheobronchial clearance in normal humans.

    PubMed Central

    Polosa, R; Hasani, A; Pavia, D; Agnew, J E; Lai, C K; Clarke, S W; Holgate, S T

    1992-01-01

    BACKGROUND: Bradykinin, a nonapeptide that contributes as a mediator to the pathogenesis of asthma, may affect lung mucociliary clearance, as it has been shown to be a potent secretagogue in canine airways and in human nasal mucosa in vivo. To evaluate this possibility the effect of inhaled bradykinin on mucociliary clearance has been studied in 10 healthy volunteers. METHODS: Subjects attended the laboratory on two occasions to take part in tracheobronchial clearance studies using a non-invasive radioisotopic technique. Inhalation of radioaerosol was followed 30 minutes later by inhalation of either bradykinin (8 mg/ml) or vehicle placebo in a randomised, double blind fashion. After each inhalation the number of coughs was recorded. Whole lung radioactivity was measured every half hour for six hours with two collimated scintillation counters, and a tracheobronchial clearance curve was plotted for each subject on each occasion. RESULTS: Mucociliary clearance, expressed as the area under the tracheobronchial radioaerosol retention curve calculated for the first six hours (AUC0-6h), was greater in nine out of 10 subjects after inhalation of bradykinin than after placebo. The median values (range) for AUC0-6h were significantly reduced from 126% (78-232%)/h with placebo to 87% (51-133%)/h with bradykinin. CONCLUSION: It is concluded that acute exposure to inhaled bradykinin accelerates tracheobronchial clearance in normal human airways. PMID:1465754

  10. Protecting effect of phytoncide solution, on normal human dermal fibroblasts against reactive oxygen species.

    PubMed

    Fujimori, Hiroaki; Hisama, Masayoshi; Shibayama, Hiroharu; Iwaki, Masahiro

    2009-01-01

    Four types of phytoncide solutions (A-Type, AB-Type, D-Type and G-Type) was evaluated for reduction of cell damage induced by oxidative stress, ultraviolet A (UVA), ultraviolet B (UVB), hydroxyperoxide (H2O2) and t-butyl-hydroperoxide (t-BHP); stimulation of collagen synthesis against UVA irradiation; and inhibition of matrix metalloproteinase-1 (MMP-1) activity induced by UVA in human normal dermal fibroblasts and human reconstituted skin model. The A-Type, AB-Type, D-Type and G-Type of phytoncide solutions pretreatment resulted in significant protection against cell damage induced by UVB, UVA, H2O2 and t-BHP. The amount of type I collagen following UVA irradiation was increased by treatment with phytoncide solutions in a concentration-dependent manner. On the other hand, phytoncide solutions also suppressed the excess MMP-1 irradiated UVA in a concentration-dependent manner. These effects of G-type solution were superior to those of other types solutions.

  11. Formation of bipolar spindles with two centrosomes in tetraploid cells established from normal human fibroblasts.

    PubMed

    Ohshima, Susumu; Seyama, Atsushi

    2012-09-01

    Tetraploid cells with unstable chromosomes frequently arise as an early step in tumorigenesis and lead to the formation of aneuploid cells. The mechanisms responsible for the chromosome instability of polyploid cells are not fully understood, although the supernumerary centrosomes in polyploid cells have been considered the major cause of chromosomal instability. The aim of this study was to examine the integrity of mitotic spindles and centrosomes in proliferative polyploid cells established from normal human fibroblasts. TIG-1 human fibroblasts were treated with demecolcine (DC) for 4 days to induce polyploidy, and the change in DNA content was monitored. Localization of centrosomes and mitotic spindles in polyploid mitotic cells was examined by immunohistochemistry and laser scanning cytometry. TIG-1 cells treated with DC became almost completely tetraploid at 2 weeks after treatment and grew at the same rate as untreated diploid cells. Most mitotic cells with 8C DNA content had only two centrosomes with bipolar spindles in established tetraploid cells, although they had four or more centrosomes with multipolar spindles at 3 days after DC treatment. The frequency of aneuploid cells increased as established tetraploid cells were propagated. These results indicate that tetraploid cells that form bipolar spindles with two centrosomes in mitosis can proliferate as diploid cells. These cells may serve as a useful model for studying the chromosome instability of polyploid cells.

  12. Characterization of mesenchymal stem cells from human normal and hyperplastic gingiva.

    PubMed

    Tang, Liang; Li, Nan; Xie, Han; Jin, Yan

    2011-03-01

    Human gingiva plays an important role in the maintenance of oral health and shows unique fetal-like scarless healing process after wounding. Here we isolate and characterize mesenchymal stem cells from human normal and hyperplastic gingival tissues (N-GMSC and H-GMSC, respectively). Immunocytochemical staining indicated that gingival lamina propria contained Stro-1 and SSEA-4 positive cells, implying existence of putative gingival MSC. Under attachment-based isolating and culturing condition, gingival MSC displayed highly clonogenic and long-term proliferative capability. By using single colony isolation and expansion approaches, we found both N-GMSC and H-GMSC possessed self-renewal and multipotent differentiation properties. N-GMSC and H-GMSC showed distinct immunoregulatory functions in a murine skin allograft setting via up-regulation of putative systemic regulatory T cells (Tregs). N-GMSC and H-GMSC were capable of regenerating collagenous tissue following in vivo transplantation, in which H-GMSC exhibited more robust regenerative capability. These findings suggest that gingival tissue contains tissue-specific mesenchymal stem cell population and is an ideal resource for immunoregulatory therapy due to its substantial availability and accessibility. In addition, gingival MSC over-activation may contribute to gingival hyperplastic phenotype.

  13. The development of hepatic stellate cells in normal and abnormal human fetuses – an immunohistochemical study

    PubMed Central

    Loo, Christine K C; Pereira, Tamara N; Pozniak, Katarzyna N; Ramsing, Mette; Vogel, Ida; Ramm, Grant A

    2015-01-01

    The precise embryological origin and development of hepatic stellate cells is not established. Animal studies and observations on human fetuses suggest that they derive from posterior mesodermal cells that migrate via the septum transversum and developing diaphragm to form submesothelial cells beneath the liver capsule, which give rise to mesenchymal cells including hepatic stellate cells. However, it is unclear if these are similar to hepatic stellate cells in adults or if this is the only source of stellate cells. We have studied hepatic stellate cells by immunohistochemistry, in developing human liver from autopsies of fetuses with and without malformations and growth restriction, using cellular Retinol Binding Protein-1 (cRBP-1), Glial Fibrillary Acidic Protein (GFAP), and α-Smooth Muscle Actin (αSMA) antibodies, to identify factors that influence their development. We found that hepatic stellate cells expressing cRBP-1 are present from the end of the first trimester of gestation and reduce in density throughout gestation. They appear abnormally formed and variably reduced in number in fetuses with abnormal mesothelial Wilms Tumor 1 (WT1) function, diaphragmatic hernia and in ectopic liver nodules without mesothelium. Stellate cells showed similarities to intravascular cells and their presence in a fetus with diaphragm agenesis suggests they may be derived from circulating stem cells. Our observations suggest circulating stem cells as well as mesothelium can give rise to hepatic stellate cells, and that they require normal mesothelial function for their development. PMID:26265759

  14. Differential Expression of Matrix-Metalloproteinase-1 and -2 Genes in Normal and Fibrotic Human Liver

    PubMed Central

    Milani, Stefano; Herbst, Hermann; Schuppan, Detlef; Grappone, Cecilia; Pellegrini, Giulia; Pinzani, Massimo; Casini, Alessandro; Calabró, Antonio; Ciancio, Giuseppe; Stefanini, Francesco; Ciancio, Andrew K.; Surrenti, Calogero

    1994-01-01

    Altered degradation of extracellular matrix has been implicated in the pathogenesis of hepatic fibrosis. We investigated levels and cellular sites of gene expression of two major collagebn-degrading enzymes, matrix-metalloproteinase (MMP)-l (fibroblast type-interstitial collagenase)and MMP-2 (72-kd gelatinase, type IV collagenase) in five normal and 18 fibrotic human livers as well as in cultured human hepatic fat-storing cells by Northern blot analysis and in situ hybridization. Fatstoring cells expressed both MMP-1 and MMP-2 RNA in vitro. In vivo, MMP-1 was undetectable in mesenchymal and parenchymal cells of all liver specimens, whereas MMP-2 transcripts were expressed in all livers by vimentin-positive, CD68 negative mesenchymal cells. Mesenchymal cells of all fibrotic livers displayed high transcript levels of transforming growth factor-β1, which is known to modulate MMP expression. Along with de novo fibrogenesis and possibly influenced by transforming growth factor-β1, expression of MMP-2 in the absence of MMP-1 expression may be responsible for the quantitative and qualitative changes of extracellular matrix observed in chronic liver disease. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 7 PMID:8129038

  15. Immunocytochemical Localization of Sex Steroid Hormone Receptors in Normal Human Mammary Gland

    PubMed Central

    Li, Sijie; Han, Bing; Liu, Guojin; Li, Songyun; Ouellet, Johanne; Labrie, Fernand; Pelletier, Georges

    2010-01-01

    The sex steroids, estrogens, progesterone, and androgens, all play a role in mammary development and function. To precisely identify the sites of action of these steroids, we studied the localization of the estrogen receptor α (ERα) and ERβ, the progesterone receptor A (PRA) and PRB, and androgen receptors (AR) in the normal human mammary gland. Immunocytochemical localization of ERα, ERβ, PRA, PRB, and AR was performed with reduction mammoplasty specimens from premenopausal women. ERα, PRA, PRB, and AR were localized mostly to the inner layer of epithelial cells lining acini and intralobular ducts, as well as to myoepithelial cells scattered in the external layer of interlobular ducts. AR was also found in some stromal cells. ERβ staining was more widespread, resulting in epithelial and myoepithelial cells being labeled in acini and ducts as well as stromal cells. These results suggest that all sex steroids can directly act on epithelial cells to modulate development and function of the human mammary gland. Estrogens and androgens can also indirectly influence epithelial cell activity by an action on stromal cells. (J Histochem Cytochem 58:509–515, 2010) PMID:20026671

  16. Human BLCAP transcript: new editing events in normal and cancerous tissues.

    PubMed

    Galeano, Federica; Leroy, Anne; Rossetti, Claudia; Gromova, Irina; Gautier, Philippe; Keegan, Liam P; Massimi, Luca; Di Rocco, Concezio; O'Connell, Mary A; Gallo, Angela

    2010-07-01

    Bladder cancer-associated protein (BLCAP) is a highly conserved protein among species, and it is considered a novel candidate tumor suppressor gene originally identified from human bladder carcinoma. However, little is known about the regulation or the function of this protein. Here, we show that the human BLCAP transcript undergoes multiple A-to-I editing events. Some of the new editing events alter the highly conserved amino terminus of the protein creating alternative protein isoforms by changing the genetically coded amino acids. We found that both ADAR1 and ADAR2-editing enzymes cooperate to edit this transcript and that different tissues displayed distinctive ratios of edited and unedited BLCAP transcripts. Moreover, we observed a general decrease in BLCAP-editing level in astrocytomas, bladder cancer and colorectal cancer when compared with the related normal tissues. The newly identified editing events, found to be downregulated in cancers, could be useful for future studies as a diagnostic tool to distinguish malignancies or epigenetic changes in different tumors.

  17. Eugenol inhibits the GABAA current in trigeminal ganglion neurons.

    PubMed

    Lee, Sang Hoon; Moon, Jee Youn; Jung, Sung Jun; Kang, Jin Gu; Choi, Seung Pyo; Jang, Jun Ho

    2015-01-01

    Eugenol has sedative, antioxidant, anti-inflammatory, and analgesic effects, but also serves as an irritant through the regulation of a different set of ion channels. Activation of gamma aminobutyric acid (GABA) receptors on sensory neurons leads to the stabilization of neuronal excitability but contributes to formalin-induced inflammatory pain. In this study, we examined the effect of eugenol on the GABA-induced current in rat trigeminal ganglia (TG) neurons and in human embryonic kidney (HEK) 293 cells expressing the GABAA receptor α1β2γ2 subtype using the whole-cell patch clamp technique. RT-PCR and Western blot analysis were used to confirm the expression of GABAA receptor γ2 subunit mRNA and protein in the TG and hippocampus. Eugenol decreased the amplitude ratio of the GABA-induced current to 27.5 ± 3.2% (p < 0.05) in TG neurons, which recovered after a 3-min washout. In HEK 293 cells expressing the α1β2γ2 subtype, eugenol inhibited GABA-induced currents in a dose-dependent manner. Application of eugenol also decreased the GABA response in the presence of a G-protein blocker. Eugenol pretreatment with different concentrations of GABA resulted in similar inhibition of the GABA-induced current in a non-competitive manner. In conclusion, eugenol inhibits the GABA-induced current in TG neurons and HEK 293 cells expressing the GABAA receptor in a reversible, dose-dependent, and non-competitive manner, but not via the G-protein pathway. We suggest that the GABAA receptor could be a molecular target for eugenol in the modulation of nociceptive information.

  18. Sirtuin 4 identification in normal human epidermal keratinocytes and its relation to sirtuin 3 and energy metabolism under normal conditions and UVB-induced stress.

    PubMed

    Dong, Kelly; Pelle, Edward; Yarosh, Daniel B; Pernodet, Nadine

    2012-03-01

    Sirtuins (SIRT) are NAD(+) -dependent deacetylases and ADP-ribosyltransferases that play a critical role in metabolism and epigenetics. SIRT3 and SIRT4 are of particular interest because they are localized in the mitochondria where energy is generated and their expression is inversely proportional to each other. Here, we report data, for the first time, demonstrating the presence of SIRT4 in normal human epidermal keratinocytes (NHEK) and confirm that its expression is inversely related to SIRT3 in these cells and that they follow a temporal cycle. Further, UVB radiation modified their expression, as well as ATP and H2 O2 levels. These deviations from the normal sirtuin cycles after UVB exposure can be an epigenetic indicator of lower metabolism levels.

  19. Trigeminal branch stimulation for the treatment of intractable craniofacial pain.

    PubMed

    Ellis, Jason A; Mejia Munne, Juan C; Winfree, Christopher J

    2015-07-01

    OBJECT Trigeminal branch stimulation has been used in the treatment of craniofacial pain syndromes. The risks and benefits of such an approach have not been clearly delineated in large studies, however. The authors report their experience in treating craniofacial pain with trigeminal branch stimulation and share the lessons they have learned after 93 consecutive electrode placements. METHODS A retrospective review of all patients who underwent trigeminal branch electrode placement by the senior author (C.J.W.) for the treatment of craniofacial pain was performed. RESULTS Thirty-five patients underwent implantation of a total of 93 trial and permanent electrodes between 2006 and 2013. Fifteen patients who experienced improved pain control after trial stimulation underwent implantation of permanent stimulators and were followed for an average of 15 months. At last follow-up 73% of patients had improvement in pain control, whereas only 27% of patients had no pain improvement. No serious complications were seen during the course of this study. CONCLUSIONS Trigeminal branch stimulation is a safe and effective treatment for a subset of patients with intractable craniofacial pain.

  20. The Influence of Trigeminal Stimulation on Children's Judgements of Odor.

    ERIC Educational Resources Information Center

    Engen, Trygg; Moskowitz, Linda

    Children's preference for odors, some of which presumably had marked trigeminal (noxious) effects, was assessed with the use of the method of pair comparison. Although the children, from 4 to 7 years old, were able to discriminate between the intensities of the odors, they were neither attracted nor repelled by them as much as the adults. In other…

  1. Pain. Part 2a: Trigeminal Anatomy Related to Pain.

    PubMed

    Renton, Tara; Egbuniwe, Obi

    2015-04-01

    In order to understand the underlying principles of orofacial pain it is important to understand the corresponding anatomy and mechanisms. Paper 1 of this series explains the central nervous and peripheral nervous systems relating to pain. The trigeminal nerve is the 'great protector' of the most important region of our body. It is the largest sensory nerve of the body and over half of the sensory cortex is responsive to any stimulation within this system. This nerve is the main sensory system of the branchial arches and underpins the protection of the brain, sight, smell, airway, hearing and taste, underpinning our very existence. The brain reaction to pain within the trigeminal system has a significant and larger reaction to the threat of, and actual, pain compared with other sensory nerves. We are physiologically wired to run when threatened with pain in the trigeminal region and it is a 'miracle' that patients volunteer to sit in a dental chair and undergo dental treatment. Clinical Relevance: This paper aims to provide the dental and medical teams with a review of the trigeminal anatomy of pain and the principles of pain assessment.

  2. Clinical Characteristics of Patients with Trigeminal Neuralgia Referred to Neurosurgery

    PubMed Central

    Siqueira, Silvia RDT; Teixeira, Manoel J; Siqueira, José TT

    2009-01-01

    Objectives To investigate the clinical characteristics of patients with trigeminal neuralgia referred to surgery in a center of reference. Methods We evaluated the general characteristics of 395 patients with trigeminal neuralgia referred to neurosurgery as treatment. They corresponded to 2 samples of 1984 and 2004. The EDOF-HC protocol (Orofacial Pain Questionnaire) and the medical profile were used. Results In the first study (1984), with 290 patients, the higher prevalence was: women (57.3%), white (95.5%), with mean age of 62.5. The most affected trigeminal branches were the maxillary and/or mandibular branches (65.5%), and the right side was the most affected (57.6%). From the second study (2004), with 105 patients, 57.1% were women, 75.2% white, with a mean age of 60.8. The maxillary and/or mandibular branches (79.0%) and the right side (69.5%) were the most affected. Both samples had neurological abnormalities and systemic diseases (mainly cardiovascular). Conclusions General characteristics of these patients were similar to other samples of trigeminal neuralgia. Neurological findings were also present in patients with no previous surgical treatment for TN. Hypertension and cardiac diseases were also frequent and make the monitoring of the patients during crises necessary. PMID:19756195

  3. Chronic dysphagia and trigeminal anesthesia after trichloroethylene exposure

    SciTech Connect

    Lawrence, W.H.; Partyka, E.K.

    1981-12-01

    A patient is described who inhaled trichloroethylene fumes while working in a closed underground pit. At the time of exposure he developed dysphagia, dysarthria and dyspnea. Assessment of his condition 11 years after the incident indicated major damage of cranial nerves, particularly the trigeminal, chronic involvement of the bulbar cranial nerves, and resultant esophageal and pharnygeal motility impairment. (JMT)

  4. [Computed tomography in the diagnosis of intracranial trigeminal neuroma].

    PubMed

    Xiao, J; Wang, D; Deng, K

    1993-12-01

    CT scans of 12 cases of intracranial trigeminal neuroma were presented. Three of the neuromas were located in petrous apex-middle cranial fossa, two in posterior cranial fossa, and 7 in both the middle and posterior cranial fossae. The tumors appeared hypo- and isodense on the plain CT scan. After contrast infusion, all tumors were well circumscribed with marked enhancement, which was homogeneous, inhomogeneous or circular. None of the trigeminal neuroma had surrounding brain edema. Of 12 cases, 10 showed change of cranial bones, which included dilatation of Meckle's cave and destructions of petrous apex, clivus and the bottom of middle cranial fossa. The tumor in one case extended to paranasopharyngeal space from the bottom of middle cranial fossa, Various features of trigeminal neuroma on CT were reviewed. Also presented were the author's experiences in differentiating intracranial trigeminal neuroma from meningiom, from pituitary adenoma spreading to parasella and glioma adjacent to cranial bottom in middle cranial fossa, and from acoustic neuroma, meningioma, cholesteatoma in cerebellopontine angle.

  5. Measurement of the distribution of anion exchange function in normal human red cells.

    PubMed Central

    Raftos, J E; Bookchin, R M; Lew, V L

    1997-01-01

    1. The aim of the present work was to investigate cell-to-cell variation in anion exchange turnover in normal human red cells. Red cells permeabilized to protons and K+ dehydrate extremely rapidly by processes that are rate-limited by the induced K+ permeability or by anion exchange turnover. Conditions were designed to render dehydration rate-limited by anion exchange turnover. Cell-to-cell variation in anion exchange function could then be measured from the distribution of delay times required for dehydrating cells to attain resistance to haemolysis in a selected hypotonic medium. 2. Red cells were suspended at 10% haematocrit in a low-K+ solution and, after a brief preincubation with 20 microM SITS at 4 degrees C, were warmed to 24 degrees C, and the protonophore CCCP was added (20 microM) followed 2 min later by valinomycin (60 microM). Delay times for cells to become resistant to lysis were measured from the instant of valinomycin addition by sampling suspension aliquots into thirty volumes of 35 mM NaCl. After centrifugation the per cent lysis was estimated by measuring the haemoglobin concentration in the supernatant. Typical median delay times with this standardized method were 4-5 min. 3. The statistical parameters of the delay time distributions report the population spread in the transport function that was limiting to dehydration. In the absence of SITS and CCCP, dehydration was limited by the diffusional Cl- permeability (PCl). Delay time distributions for PCl- and anion exchange-limited dehydration were measured in red cells from three normal donors. For both distributions, the coefficients of variation ranged between 13.0 and 15.2%, indicating a high degree of uniformity in PCl and anion exchange function among individual red cells. PMID:9061637

  6. The Shape of the Ganglion Cell plus Inner Plexiform Layers of the Normal Human Macula

    PubMed Central

    Knighton, Robert W.; Gregori, Giovanni

    2012-01-01

    Purpose. To use surfaces generated by two-dimensional penalized splines (2D P-splines) to characterize the shape of the macular ganglion cell plus inner plexiform layers (GCL+IPL) in a group of normal humans. Methods. Macular images of the right eyes of 23 normal subjects ranging in age from 18 to 75 years were obtained with spectral-domain optical coherence tomography (SD-OCT). The thickness of GCL+IPL was determined by manual segmentation, areas with blood vessels were removed, and the resulting maps were fit by smooth surfaces in polar coordinates centered on the fovea. Results. Smooth surfaces based on 2D P-splines could precisely represent GCL+IPL thickness data, with errors comparable to the axial resolution of the SD-OCT instrument. Metrics were developed for the size, shape, and slope of the edge of the foveal depression and size and shape of the surrounding macular ridge. The slope of the foveal edge was negatively correlated with foveal size (r = −0.60). The size of the macular ridge was positively correlated with foveal size (r = 0.75), with a slope near unity (0.90 ± 0.18). The centroids of the foveal edge and macular ridge clustered near the foveal center. The foveal edge and macular ridge were well fit by ellipses. The mean GCL+IPL thickness formed an elliptical annulus elongated by approximately 30% in the horizontal direction. Conclusions. The methods developed here provide precise characterization of retinal layers for the study of glaucoma, foveal development, and other applications. PMID:23033389

  7. Serial biomechanical comparison of edematous, normal, and collagen crosslinked human donor corneas using optical coherence elastography

    PubMed Central

    Ford, Matthew R.; Roy, Abhijit Sinha; Rollins, Andrew M.; Dupps, William J.

    2014-01-01

    PURPOSE To noninvasively evaluate the effects of corneal hydration and collagen crosslinking (CXL) on the mechanical behavior of the cornea. SETTING Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, USA. DESIGN Experimental study. METHODS An optical coherence elastography (OCE) technique was used to measure the displacement behavior of 5 pairs of debrided human donor globes in 3 serial states as follows: edematous, normal thickness, and after riboflavin–ultraviolet-A–mediated CXL. During micromotor-controlled axial displacements with a curved goniolens at physiologic intraocular pressure (IOP), serial optical coherence tomography scans were obtained to allow high-resolution intrastromal speckle tracking and displacement measurements over the central 4.0 mm of the cornea. RESULTS With no imposed increase in IOP, the mean lateral to imposed axial displacement ratios were 0.035 μm/μm ± 0.037 (SD) in edematous corneas, 0.021 ± 0.02 μm/μm in normal thickness corneas, and 0.014 ± 0.009 μm/μm in post-CXL corneas. The differences were statistically significant (P<.05, analysis of variance) and indicated a 40% increase in lateral stromal resistance with deturgescence and a further 33% mean increase in relative stiffness with CXL. CONCLUSIONS Serial perturbations of the corneal hydration state and CXL had significant effects on corneal biomechanical behavior. With an axially applied stress from a nonapplanating contact lens, displacements along the direction of the collagen lamellae were 2 orders of magnitude lower than axial deformations. These experiments show the ability of OCE to quantify clinically relevant mechanical property differences under physiologic conditions. Financial Disclosures Proprietary or commercial disclosures are listed after the references. PMID:24767794

  8. Aneuploidy and DNA replication in the normal human brain and Alzheimer's disease.

    PubMed

    Mosch, Birgit; Morawski, Markus; Mittag, Anja; Lenz, Dominik; Tarnok, Attila; Arendt, Thomas

    2007-06-27

    Reactivation of the cell cycle, including DNA replication, might play a major role in Alzheimer's disease (AD). A more than diploid DNA content in differentiated neurons might alternatively result from chromosome mis-segregation during mitosis in neuronal progenitor cells. It was our objective to distinguish between these two mechanisms for aneuploidy and to provide evidence for a functional cell cycle in AD. Using slide-based cytometry, chromogenic in situ hybridization, and PCR amplification of alu-repeats, we quantified the DNA amount of identified cortical neurons in normal human brain and AD and analyzed the link between a tetraploid DNA content and expression of the early mitotic marker cyclin B1. In the normal brain, the number of neurons with a more than diploid content amounts to approximately 10%. Less than 1% of neurons contains a tetraploid DNA content. These neurons do not express cyclin B1, most likely representing constitutional tetraploidy. This population of cyclin B1-negative tetraploid neurons, at a reduced number, is also present in AD. In addition, a population of cyclin B1-positive tetraploid neurons of approximately 2% of all neurons was observed in AD. Our results indicate that at least two different mechanisms need to be distinguished giving rise to a tetraploid DNA content in the adult brain. Constitutional aneuploidy in differentiated neurons might be more frequent than previously thought. It is, however, not elevated in AD. In addition, in AD some neurons have re-entered the cell cycle and entirely passed through a functional interphase with a complete DNA replication.

  9. Expression Profiles of miRNA Subsets Distinguish Human Colorectal Carcinoma and Normal Colonic Mucosa

    PubMed Central

    Pellatt, Daniel F; Stevens, John R; Wolff, Roger K; Mullany, Lila E; Herrick, Jennifer S; Samowitz, Wade; Slattery, Martha L

    2016-01-01

    OBJECTIVES: MicroRNAs (miRNAs) are small, non-protein-coding RNA molecules that are commonly dysregulated in colorectal tumors. The objective of this study was to identify smaller subsets of highly predictive miRNAs. METHODS: Data come from population-based studies of colorectal cancer conducted in Utah and the Kaiser Permanente Medical Care Program. Tissue samples were available for 1,953 individuals, of which 1,894 had carcinoma tissue and 1,599 had normal mucosa available for statistical analysis. Agilent Human miRNA Microarray V.19.0 was used to generate miRNA expression profiles; validation of expression levels was carried out using quantitative PCR. We used random forest analysis and verified findings with logistic modeling in separate data sets. Important microRNAs are identified and bioinformatics tools are used to identify target genes and related biological pathways. RESULTS: We identified 16 miRNAs for colon and 17 miRNAs for rectal carcinoma that appear to differentiate between carcinoma and normal mucosa; of these, 12 were important for both colon and rectal cancer, hsa-miR-663b, hsa-miR-4539, hsa-miR-17-5p, hsa-miR-20a-5p, hsa-miR-21-5p, hsa-miR-4506, hsa-miR-92a-3p, hsa-miR-93-5p, hsa-miR-145-5p, hsa-miR-3651, hsa-miR-378a-3p, and hsa-miR-378i. Estimated misclassification rates were low at 4.83% and 2.5% among colon and rectal observations, respectively. Among independent observations, logistic modeling reinforced the importance of these miRNAs, finding the primary principal components of their variation statistically significant (P<0.001 among both colon and rectal observations) and again producing low misclassification rates. Repeating our analysis without those miRNAs initially identified as important identified other important miRNAs; however, misclassification rates increased and distinctions between remaining miRNAs in terms of classification importance were reduced. CONCLUSIONS: Our data support the hypothesis that while many miRNAs are

  10. Dramatic Increase in Oxidative Stress in Carbon-Irradiated Normal Human Skin Fibroblasts

    PubMed Central

    Laurent, Carine; Leduc, Alexandre; Pottier, Ivannah; Prévost, Virginie; Sichel, François; Lefaix, Jean-Louis

    2013-01-01

    Skin complications were recently reported after carbon-ion (C-ion) radiation therapy. Oxidative stress is considered an important pathway in the appearance of late skin reactions. We evaluated oxidative stress in normal human skin fibroblasts after carbon-ion vs. X-ray irradiation. Survival curves and radiobiological parameters were calculated. DNA damage was quantified, as were lipid peroxidation (LPO), protein carbonylation and antioxidant enzyme activities. Reduced and oxidized glutathione ratios (GSH/GSSG) were determined. Proinflammatory cytokine secretion in culture supernatants was evaluated. The relative biological effectiveness (RBE) of C-ions vs. X-rays was 4.8 at D0 (irradiation dose corresponding to a surviving fraction of 37%). Surviving fraction at 2 Gy (SF2) was 71.8% and 7.6% for X-rays and C-ions, respectively. Compared with X-rays, immediate DNA damage was increased less after C-ions, but a late increase was observed at D10% (irradiation dose corresponding to a surviving fraction of 10%). LPO products and protein carbonyls were only increased 24 hours after C-ions. After X-rays, superoxide dismutase (SOD) activity was strongly increased immediately and on day 14 at D0% (irradiation dose corresponding to a surviving fraction of around 0%), catalase activity was unchanged and glutathione peroxidase (GPx) activity was increased only on day 14. These activities were decreased after C-ions compared with X-rays. GSH/GSSG was unchanged after X-rays but was decreased immediately after C-ion irradiation before an increase from day 7. Secretion of IL-6 was increased at late times after X-ray irradiation. After C-ion irradiation, IL-6 concentration was increased on day 7 but was lower compared with X-rays at later times. C-ion effects on normal human skin fibroblasts seemed to be harmful in comparison with X-rays as they produce late DNA damage, LPO products and protein carbonyls, and as they decrease antioxidant defences. Mechanisms leading to this

  11. Morphine Increases Acetylcholine Release in the Trigeminal Nuclear Complex

    PubMed Central

    Zhu, Zhenghong; Bowman, Heather R.; Baghdoyan, Helen A.; Lydic, Ralph

    2008-01-01

    Study Objectives: The trigeminal nuclear complex (V) contains cholinergic neurons and includes the principal sensory trigeminal nucleus (PSTN) which receives sensory input from the face and jaw, and the trigeminal motor nucleus (MoV) which innervates the muscles of mastication. Pain associated with pathologies of V is often managed with opioids but no studies have characterized the effect of opioids on acetylcholine (ACh) release in PSTN and MoV. Opioids can increase or decrease ACh release in brainstem nuclei. Therefore, the present experiments tested the 2-tailed hypothesis that microdialysis delivery of opioids to the PSTN and MoV significantly alters ACh release. Design: Using a within-subjects design and isoflurane-anesthetized Wistar rats (n = 53), ACh release in PSTN during microdialysis with Ringer's solution (control) was compared to ACh release during dialysis delivery of the sodium channel blocker tetrodotoxin, muscarinic agonist bethanechol, opioid agonist morphine, mu opioid agonist DAMGO, antagonists for mu (naloxone) and kappa (nor-binaltorphimine; nor-BNI) opioid receptors, and GABAA antagonist bicuculline. Measurements and Results: Tetrodotoxin decreased ACh, confirming action potential-dependent ACh release. Bethanechol and morphine caused a concentration-dependent increase in PSTN ACh release. The morphine-induced increase in ACh release was blocked by nor-BNI but not by naloxone. Bicuculline delivered to the PSTN also increased ACh release. ACh release in the MoV was increased by morphine, and this increase was not blocked by naloxone or nor-BNI. Conclusions: These data comprise the first direct measures of ACh release in PSTN and MoV and suggest synaptic disinhibition as one possible mechanism by which morphine increases ACh release in the trigeminal nuclei. Citation: Zhu Z; Bowman HR; Baghdoyan HA; Lydic R. Morphine increases acetylcholine release in the trigeminal nuclear complex. SLEEP 2008;31(12):1629–1637. PMID:19090318

  12. Production of glycosylated physiologically "normal" human alpha 1-antitrypsin by mouse fibroblasts modified by insertion of a human alpha 1-antitrypsin cDNA using a retroviral vector.

    PubMed Central

    Garver, R I; Chytil, A; Karlsson, S; Fells, G A; Brantly, M L; Courtney, M; Kantoff, P W; Nienhuis, A W; Anderson, W F; Crystal, R G

    1987-01-01

    Alpha 1-Antitrypsin (alpha 1AT) deficiency is a hereditary disorder characterized by reduced serum levels of alpha 1AT, resulting in destruction of the lower respiratory tract by neutrophil elastase. As an approach to augment alpha 1AT levels in this disorder with physiologically normal human alpha 1AT, we have integrated a full-length normal human alpha 1AT cDNA into the genome of mouse fibroblasts. To accomplish this, the retroviral vector N2 was modified by inserting the simian virus 40 early promoter followed by the alpha 1AT cDNA. Southern analysis demonstrated that the intact cDNA was present in the genome of selected clones of the transfected murine fibroblasts psi 2 and infected NIH 3T3. The clones produced three mRNA transcripts (5.8, 4.8, and 2.4 kilobases) containing human alpha 1AT sequences, secreted an alpha 1AT molecule recognized by an anti-human alpha 1AT antibody, with the same molecular mass (52 kDa) as normal human alpha 1AT and that complexed with and inhibited human neutrophil elastase. The psi 2 produced alpha 1AT was glycosylated, and when infused intravenously into mice, it had a serum half-life similar to normal alpha 1AT purified from human plasma and markedly longer than that of nonglycosylated human alpha 1AT cDNA-directed yeast-produced alpha 1AT. These studies demonstrate the feasibility of using a retroviral vector to insert the normal human alpha 1AT cDNA into non-alpha 1AT-producing cells, resulting in the synthesis and secretion of physiologically "normal" human alpha 1AT. Images PMID:3029759

  13. A Gain-of-Function Mutation in Nav1.6 in a Case of Trigeminal Neuralgia

    PubMed Central

    Tanaka, Brian S; Zhao, Peng; Dib-Hajj, Fadia B; Morisset, Valerie; Tate, Simon; Waxman, Stephen G; Dib-Hajj, Sulayman D

    2016-01-01

    Idiopathic trigeminal neuralgia (TN) is a debilitating pain disorder characterized by episodic unilateral facial pain along the territory of branches of the trigeminal nerve. Human pain disorders, but not TN, have been linked to gain-of-function mutations in peripheral voltage-gated sodium channels (NaV1.7, NaV1.8 and NaV1.9). Gain-of-function mutations in NaV1.6, which is expressed in myelinated and unmyelinated central nervous system (CNS) and peripheral nervous system neurons and supports neuronal high-frequency firing, have been linked to epilepsy but not to pain. Here, we describe an individual who presented with evoked and spontaneous paroxysmal unilateral facial pain and carried a diagnosis of TN. Magnetic resonance imaging showed unilateral neurovascular compression, consistent with pain in areas innervated by the second branch of the trigeminal nerve. Genetic analysis as part of a phase 2 clinical study in patients with TN conducted by Convergence Pharmaceuticals Ltd revealed a previously undescribed de novo missense mutation in NaV1.6 (c.A406G; p.Met136Val). Whole-cell voltage-clamp recordings show that the Met136Val mutation significantly increases peak current density (1.5-fold) and resurgent current (1.6-fold) without altering gating properties. Current-clamp studies in trigeminal ganglia (TRG) neurons showed that Met136Val increased the fraction of high-firing neurons, lowered the current threshold and increased the frequency of evoked action potentials in response to graded stimuli. Our results demonstrate a novel NaV1.6 mutation in TN, and show that this mutation potentiates transient and resurgent sodium currents and leads to increased excitability in TRG neurons. We suggest that this gain-of-function NaV1.6 mutation may exacerbate the pathophysiology of vascular compression and contribute to TN. PMID:27496104

  14. Metabolic fate of radiolabeled prostaglandin D2 in a normal human male volunteer

    SciTech Connect

    Liston, T.E.; Roberts, L.J. 2d.

    1985-10-25

    50 microCi of (TH)prostaglandin D2 tracer (100 Ci/mmol) was infused intravenously into a normal human male volunteer. 75% of the infused radioactivity was excreted into the urine within 5 h. This urine was added to urine obtained from two mastocytosis patients with marked overproduction of prostaglandin D2. Radiolabeled prostaglandin D2 urinary metabolites were chromatographically isolated and purified and subsequently identified by gas chromatography-mass spectrometry. 25 metabolites were identified. 23 of these compounds comprising 37% of the recovered radioactivity had prostaglandin F-ring structures, and only two metabolites comprising 2.7% of the recovered radioactivity retained the prostaglandin D-ring structure. The single most abundant metabolite identified was 9,11-dihydroxy-15-oxo-2,3,18,19-tetranorprost-5-ene-1,20-dioic acid which was isolated in a tricyclic form as a result of formation of a lower side chain hemiketal followed by lactonization of the terminal carboxyl and the hemiketal hydroxyl. Different isomeric forms of several prostaglandin F-ring metabolites were identified. An isomer of prostaglandin F2 alpha was also excreted intact into the urine as a metabolite of prostaglandin D2. 15 PGF-ring compounds were treated with n-butylboronic acid and 13 failed to form a boronate derivative, suggesting that the orientation of the hydroxyl group at C-11 in these 13 metabolites is beta. This study documents that prostaglandin D2 is metabolized to prostaglandin F-ring metabolites in vivo in humans. These results also bring into question the accuracy of quantifying prostaglandin F2 alpha metabolites as a specific index of endogenous prostaglandin F2 alpha biosynthesis, as well as quantifying urinary prostaglandin F2 alpha as an accurate index of renal production of prostaglandin F2 alpha.

  15. Activation of the Innate Immune Response against DENV in Normal Non-Transformed Human Fibroblasts

    PubMed Central

    Bustos-Arriaga, José; García-Machorro, Jazmín; León-Juárez, Moisés; García-Cordero, Julio; Santos-Argumedo, Leopoldo; Flores-Romo, Leopoldo; Méndez-Cruz, A. René; Juárez-Delgado, Francisco J.; Cedillo-Barrón, Leticia

    2011-01-01

    Background When mosquitoes infected with DENV are feeding, the proboscis must traverse the epidermis several times (“probing”) before reaching a blood vessel in the dermis. During this process, the salivary glands release the virus, which is likely to interact first with cells of the various epidermal and dermal layers, cells which could be physiologically relevant to DENV infection and replication in humans. However, important questions are whether more abundant non-hematopoietic cells such as fibroblasts become infected, and whether they play any role in antiviral innate immunity in the very early stages of infection, or even if they might be used by DENV as primary replication cells. Methodology/Principal Findings Fibroblasts freshly released from healthy skin and infected 12 hours after their isolation show a positive signal for DENV. In addition, when primary skin fibroblast cultures were established and subsequently infected, we showed DENV-2 antigen-positive intracellular signal at 24 hours and 48 hours post-infection. Moreover, the fibroblasts showed productive infection in a conventional plaque assay. The skin fibroblasts infected with DENV-2 underwent potent signaling through both TLR3 and RIG- 1, but not Mda5, triggering up-regulation of IFNβ, TNFα, defensin 5 (HB5) and β defensin 2 (HβD2). In addition, DENV infected fibroblasts showed increased nuclear translocation of interferon (IFN) regulatory factor 3 (IRF3), but not interferon regulatory factor 7 (IRF7), when compared with mock-infected fibroblasts. Conclusions/Significance In this work, we demonstrated the high susceptibility to DENV infection by primary fibroblasts from normal human skin, both in situ and in vitro. Our results suggest that these cells may contribute to the pro-inflammatory and anti-viral microenvironment in the early stages of interaction with DENV-2. Furthermore, the data suggest that fibroblast may also be used as a primary site of DENV replication and provide viral

  16. Differential Activation of Signaling Pathways by UVA and UVB Radiation in Normal Human Epidermal Keratinocytes†

    PubMed Central

    Syed, Deeba N.; Afaq, Farrukh; Mukhtar, Hasan

    2012-01-01

    Ultraviolet (UV) radiation from the solar spectrum is a major etiological factor for many cutaneous pathologies including cancer. By understanding changes in cell signaling pathways induced by UVA and UVB, novel strategies for prevention and treatment of UV-related pathologies could be developed. However, much of the information in the literature from various laboratories cannot cross talk because of difficulties associated with the use of ill-defined light sources and physiologically irrelevant light dosimetry. Herein, we have assessed the effect of exposure of normal human epidermal keratinocytes (NHEK) to UVA (2 and 4 J cm−2) or UVB (20 and 40 mJ cm−2) radiation. Employing western blot analysis, we found that exposure of NHEK to UVB, but not UVA, phosphorylates JNK1/2 at Th183/Tyr185, STAT3 at Ser727, AKT at Ser473 and increases c-Fos expression, whereas exposure to UVA, but not UVB, phosphorylates AKT at Thr308. UVB as well as UVA exposure leads to increased phosphorylation of (1) ERK1/2 at Th202/Tyr204; (2) p38 at Th180/Tyr204; (3) STAT3 at Tyr705; (4) mTOR at Thr2448; and (v) p70S6k at Thr421/Ser424; enhanced expression of PI3K (p85) and c-jun; and nuclear translocation of NFκB proteins. These findings could be considered as a beginning for understanding the differential effects of UVA and UVB in the human skin and may have implications both with respect to risk assessment from exposure to solar UV radiation, and to target interventions against signaling events mediated by UVA and UVB. PMID:22335604

  17. Regulation of nutrition-associated receptors in blood monocytes of normal weight and obese humans.

    PubMed

    Pivovarova, Olga; Hornemann, Silke; Weimer, Sandra; Lu, Ye; Murahovschi, Veronica; Zhuk, Sergei; Seltmann, Anne-Cathrin; Malashicheva, Anna; Kostareva, Anna; Kruse, Michael; Busjahn, Andreas; Rudovich, Natalia; Pfeiffer, Andreas F H

    2015-03-01

    Obesity, type 2 diabetes and associated metabolic diseases are characterized by low-grade systemic inflammation which involves interplay of nutrition and monocyte/macrophage functions. We suggested that some factors such as nutrient components, neuropeptides involved in the control of gastrointestinal functions, and gastrointestinal hormones might influence immune cell functions and in this way contribute to the disease pathogenesis. The aim of this study was to investigate the mRNA expression of twelve nutrition-associated receptors in peripheral blood mononuclear cells (PBMC), isolated monocytes and monocyte-derived macrophages and their regulation under the switching from the high-carbohydrate low-fat diet to the low-carbohydrate high-fat (LC/HFD) isocaloric diet in healthy humans. The mRNA expression of receptors for short chain fatty acids (GPR41, GPR43), bile acids (TGR5), incretins (GIPR, GLP1R), cholecystokinin (CCKAR), neuropeptides VIP and PACAP (VIPR1, VIPR2), and neurotensin (NTSR1) was detected in PBMC and monocytes, while GPR41, GPR43, GIPR, TGR5, and VIPR1 were found in macrophages. Correlations of the receptor expression in monocytes with a range of metabolic and inflammatory markers were found. In non-obese subjects, the dietary switch to LC/HFD induced the increase of GPR43 and VIPR1 expression in monocytes. No significant differences of receptor expression between normal weight and moderately obese subjects were found. Our study characterized for the first time the expression pattern of nutrition-associated receptors in human blood monocytes and its dietary-induced changes linking metabolic responses to nutrition with immune functions in health and metabolic diseases.

  18. Cell surface glycopeptides from human intestinal epithelial cell lines derived from normal colon and colon adenocarcinomas

    SciTech Connect

    Youakim, A.; Herscovics, A.

    1985-11-01

    The cell surface glycopeptides from an epithelial cell line (CCL 239) derived from normal human colon were compared with those from three cell lines (HCT-8R, HCT-15, and CaCo-2) derived independently from human colonic adenocarcinomas. Cells were incubated with D-(2-TH)mannose or L-(5,6-TH)fucose for 24 h and treated with trypsin to release cell surface components which were then digested exhaustively with Pronase and fractionated on Bio-Gel P-6 before and after treatment with endo-beta-N-acetylglucosaminidase H. The most noticeable difference between the labeled glycopeptides from the tumor and CCL 239 cells was the presence in the former of an endo-beta-N-acetylglucosaminidase H-resistant high molecular weight glycopeptide fraction which was eluted in the void volume of Bio-Gel P-6. This fraction was obtained with both labeled mannose and fucose as precursors. However, acid hydrolysis of this fraction obtained after incubation with (2-TH)mannose revealed that as much as 60-90% of the radioactivity was recovered as fucose. Analysis of the total glycopeptides (cell surface and cell pellet) obtained after incubation with (2-TH)mannose showed that from 40-45% of the radioactivity in the tumor cells and less than 10% of the radioactivity in the CCL 239 cells was recovered as fucose. After incubation of the HCT-8R cells with D-(1,6-TH)glucosamine and L-(1- UC)fucose, strong acid hydrolysis of the labeled glycopeptide fraction excluded from Bio-Gel P-6 produced TH-labeled N-acetylglucosamine and N-acetylgalactosamine.

  19. Epigenetic regulation of normal human mammary cell type-specific miRNAs

    SciTech Connect

    Vrba, Lukas; Garbe, James C.; Stampfer, Martha R.; Futscher, Bernard W.

    2011-08-26

    Epigenetic mechanisms are important regulators of cell type–specific genes, including miRNAs. In order to identify cell type-specific miRNAs regulated by epigenetic mechanisms, we undertook a global analysis of miRNA expression and epigenetic states in three isogenic pairs of human mammary epithelial cells (HMEC) and human mammary fibroblasts (HMF), which represent two differentiated cell types typically present within a given organ, each with a distinct phenotype and a distinct epigenotype. While miRNA expression and epigenetic states showed strong interindividual concordance within a given cell type, almost 10% of the expressed miRNA showed a cell type–specific pattern of expression that was linked to the epigenetic state of their promoter. The tissue-specific miRNA genes were epigenetically repressed in nonexpressing cells by DNA methylation (38%) and H3K27me3 (58%), with only a small set of miRNAs (21%) showing a dual epigenetic repression where both DNA methylation and H3K27me3 were present at their promoters, such as MIR10A and MIR10B. Individual miRNA clusters of closely related miRNA gene families can each display cell type–specific repression by the same or complementary epigenetic mechanisms, such as the MIR200 family, and MIR205, where fibroblasts repress MIR200C/141 by DNA methylation, MIR200A/200B/429 by H3K27me3, and MIR205 by both DNA methylation and H3K27me3. Since deregulation of many of the epigenetically regulated miRNAs that we identified have been linked to disease processes such as cancer, it is predicted that compromise of the epigenetic control mechanisms is important for this process. Overall, these results highlight the importance of epigenetic regulation in the control of normal cell type–specific miRNA expression.

  20. RNA Sequencing of Trigeminal Ganglia in Rattus Norvegicus after Glyceryl Trinitrate Infusion with Relevance to Migraine

    PubMed Central

    Hougaard Pedersen, Sara; Maretty, Lasse; Ramachandran, Roshni; Sibbesen, Jonas Andreas; Yakimov, Victor; Elgaard-Christensen, Rikke; Hansen, Thomas Folkmann; Krogh, Anders; Olesen, Jes; Jansen-Olesen, Inger

    2016-01-01

    Introduction Infusion of glyceryl trinitrate (GTN), a donor of nitric oxide, induces immediate headache in humans that in migraineurs is followed by a delayed migraine attack. In order to achieve increased knowledge of mechanisms activated during GTN-infusion this present study aims to investigate transcriptional responses to GTN-infusion in the rat trigeminal ganglia. Methods Rats were infused with GTN or vehicle and trigeminal ganglia were isolated either 30 or 90 minutes post infusion. RNA sequencing was used to investigate transcriptomic changes in response to the treatment. Furthermore, we developed a novel method for Gene Set Analysis Of Variance (GSANOVA) to identify gene sets associated with transcriptional changes across time. Results 15 genes displayed significant changes in transcription levels in response to GTN-infusion. Ten of these genes showed either sustained up- or down-regulation in the 90-minute period after infusion. The GSANOVA analysis demonstrate enrichment of pathways pointing towards an increase in immune response, signal transduction, and neuroplasticity in response to GTN-infusion. Future functional in-depth studies of these mechanisms are expected to increase our understanding of migraine pathogenesis. PMID:27213950

  1. Photobiomodulation on the proliferation and collagen synthesis of normal human skin fibroblast cells

    NASA Astrophysics Data System (ADS)

    Cheng, Lei; Liu, Timon Cheng-Yi; Chi, Jin-Quan; Li, Yan; Jin, Hua

    2006-01-01

    Background and Objective: Cultured normal human skin fibroblast cells (HSFs) were once used to study the mechanism of the effects of low intensity He-Ne laser irradiation (LHNL) on wound healing. The proliferation and collagen synthesis of HFSs were modulated by LHNL in different papers, respectively, and both of them are studied in this paper. Study Design/Materials and Methods: The dosage was studied for the same radiation time 300s. The proliferation and collagen synthesis were measured by 3-[4,5-Dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay and the spectrophotometric method for the determination of hydroxyproline, respectively. Results: The dose zones were called dose 1, dose 2 and dose 3 from low dose on so that HSF proliferation was inhibited in dose 1 (16, 24 mJ/cm2), and promoted in dose 2 (298, 503, 597mJ/cm2), and the collagen synthesis was inhibited in dose 2 (401, 526 mJ/cm2), and promoted in dose 3 (714, 926, 1539, 1727mJ/cm2), which supports our biological model of photobiomodulation. It was found there is the linear relationship of the effect with dose with dose in each dose zone. Conclusions: The photobiomodulation on the proliferation and collagen synthesis of HSFs might be linearly dose-dependent in limited dosage with radiation time kept constant, which provides a foundation to discuss photobiomodulation on wound healing.

  2. Sarcoplasmic reticulum-associated cyclic adenosine 5'-monophosphate phosphodiesterase activity in normal and failing human hearts.

    PubMed Central

    Movsesian, M A; Smith, C J; Krall, J; Bristow, M R; Manganiello, V C

    1991-01-01

    Sarcoplasmic reticulum-associated cAMP phosphodiesterase activity was examined in microsomes prepared from the left ventricular myocardium of eight heart transplant recipients with end-stage idiopathic dilated cardiomyopathy and six unmatched organ donors with normal cardiac function. At cAMP concentrations less than or equal to 1.0 microM, sarcoplasmic reticulum-associated cAMP phosphodiesterase activity was functionally homogeneous. cAMP phosphodiesterase activity was inhibited competitively by cGMP (Ki = 0.031 +/- 0.008 microM) and the cilostamide derivative OPC 3911 (Ki = 0.018 +/- 0.004 microM), but was essentially insensitive to rolipram. Vmax and Km were 781.7 +/- 109.2 nmol/mg per min and 0.188 +/- 0.031 microM, respectively, in microsomes prepared from nonfailing hearts and 793.9 +/- 68.9 nmol/mg per min and 0.150 +/- 0.027 microM in microsomes prepared from failing hearts. Microsomes prepared from nonfailing and failing hearts did not differ with respect to either the ratio of cAMP phosphodiesterase activity to ATP-dependent Ca2+ accumulation activity or the sensitivity of cAMP phosphodiesterase activity to inhibition by OPC 3911. These data suggest that the diminished inotropic efficacy of phosphodiesterase inhibitors in failing human hearts does not result from changes in the level, kinetic properties, or pharmacologic sensitivity of sarcoplasmic reticulum-associated cAMP phosphodiesterase activity. PMID:1647414

  3. Normal human oral keratinocytes demonstrate abnormal DNA end joining activity during replicative senescence.

    PubMed

    Kang, Mo K; Shin, Ki-Hyuk; Yip, Felix K; Park, No-Hee

    2005-04-01

    Repair of DNA double-strand breaks (DSBs) is critical for the maintenance of cellular genetic integrity. DSBs are repaired by cellular end joining activity, which could proceed with varying degrees of accuracy. Abnormal end joining may lead to an accumulation of mutations and contribute to genetic instability and cellular aging. In the present study, we compared the efficiency and accuracy of end joining activities in exponentially replicating and senescing normal human oral keratinocytes (NHOK). We developed an in vitro end joining assay utilizing a plasmid linearized with a unique EcoR I or EcoR V restriction site. The efficiency of end joining was determined by PCR with primers that could amplify the fragment containing the end joining site. The accuracy of end joining was assessed by determining whether the original EcoR I site was restored after end joining. Both replicating and senescing cultures of NHOK yielded a similar level of end joining efficiency, which was noted by the similar intensity of PCR amplification. However, the frequency of end joining errors was significantly elevated in NHOK during replicative senescence. Senescing NHOK could thus accumulate abnormal end joining products, which might contribute to cellular aging and cancer.

  4. Immunohistochemical expression of doublecortin in the human cerebrum: comparison of normal development and neuronal migration disorders.

    PubMed

    Qin, J; Mizuguchi, M; Itoh, M; Takashima, S

    2000-04-28

    Immunohistochemical expression of the doublecortin (DCX) gene product was investigated in cerebral cortices from 33 normal developing human, aged 9 gestational weeks (GW) to 29 years, and from 26 patients with various neuronal migration disorders, aged 19 GW to 34 years. DCX immunoreactivity was detected predominantly in the fetal cerebral cortex. The neurons in the cortical plate (CP) exhibited positive labeling at 9 GW. Staining was the most marked intense at 12-20 GW, and gradually decreased thereafter, only relatively weak immunoreactivity remaining in pyramidal cells. Comparison of the immunohistochemical characteristics of DCX and those of nestin and vimentin indicated the early expression of DCX in neuroepithelial stem cells of the subventricular germinal layer, as well as in neurons of the CP. The most marked intense expression in the period of neuronal migration strongly indicated its role in neuronal migration. The abnormal distribution of DCX immunolabeling in the cerebral cortex was associated with a neuronal disarrangement in some migration disorders, such as Miller-Dieker syndrome and Fukuyama congenital muscular dystrophy. Decreased DCX immunolabeling was demonstrated in fetuses and infants with Zellweger syndrome, implicating DCX in the neuronal migration abnormality in this syndrome.

  5. Looking at images with human figures: comparison between autistic and normal children.

    PubMed

    van der Geest, J N; Kemner, C; Camfferman, G; Verbaten, M N; van Engeland, H

    2002-04-01

    Based on clinical observations of abnormal gaze behavior of autistic children, it has been suggested that autistic children have a problem in processing social information. Several studies on eye movements have indeed found indications that children with autism show particularly abnormal gaze behavior in relation to social stimuli. However, the methodology used in such investigations did not allow for precise gaze analysis. In the present study, the looking behavior of autistic children toward cartoon-like scenes that included a human figure was measured quantitatively using an infrared eye-tracking device. Fixation behavior of autistic children was similar to that of their age- and IQ-matched normal peers. These results do not support the notion that autistic children have a specific problem in processing socially loaded visual stimuli. Also, there is no indication for an abnormality in gaze behavior in relation to neutral objects. It is suggested that the often-reported abnormal use of gaze in everyday life is not related to the nature of the visual stimuli but that other factors, like social interaction, may play a decisive role.

  6. Evidence of disrupted high-risk human papillomavirus DNA in morphologically normal cervices of older women.

    PubMed

    Leonard, Sarah M; Pereira, Merlin; Roberts, Sally; Cuschieri, Kate; Nuovo, Gerard; Athavale, Ramanand; Young, Lawrence; Ganesan, Raji; Woodman, Ciarán B

    2016-02-15

    High-risk human papillomavirus (HR-HPV) causes nearly 100% of cervical carcinoma. However, it remains unclear whether HPV can establish a latent infection, one which may be responsible for the second peak in incidence of cervical carcinoma seen in older women. Therefore, using Ventana in situ hybridisation (ISH), quantitative PCR assays and biomarkers of productive and transforming viral infection, we set out to provide the first robust estimate of the prevalence and characteristics of HPV genomes in FFPE tissue from the cervices of 99 women undergoing hysterectomy for reasons unrelated to epithelial abnormality. Our ISH assay detected HR-HPV in 42% of our study population. The majority of ISH positive samples also tested HPV16 positive using sensitive PCR based assays and were more likely to have a history of preceding cytological abnormality. Analysis of subsets of this population revealed HR-HPV to be transcriptionally inactive as there was no evidence of a productive or transforming infection. Critically, the E2 gene was always disrupted in those HPV16 positive cases which were assessed. These findings point to a reservoir of transcriptionally silent, disrupted HPV16 DNA in morphologically normal cervices, re-expression of which could explain the increase in incidence of cervical cancer observed in later life.

  7. Nonlinear dynamics in pulsatile secretion of parathyroid hormone in normal human subjects

    NASA Astrophysics Data System (ADS)

    Prank, Klaus; Harms, Heio; Brabant, Georg; Hesch, Rolf-Dieter; Dämmig, Matthias; Mitschke, Fedor

    1995-03-01

    In many biological systems, information is transferred by hormonal ligands, and it is assumed that these hormonal signals encode developmental and regulatory programs in mammalian organisms. In contrast to the dogma of endocrine homeostasis, it could be shown that the biological information in hormonal networks is not only present as a constant hormone concentration in the circulation pool. Recently, it has become apparent that hormone pulses contribute to this hormonal pool, which modulates the responsiveness of receptors within the cell membrane by regulation of the receptor synthesis, movement within the membrane layer, coupling to signal transduction proteins and internalization. Phase space analysis of dynamic parathyroid hormone (PTH) secretion allowed the definition of a (in comparison to normal subjects) relatively quiet ``low dynamic'' secretory pattern in osteoporosis, and a ``high dynamic'' state in hyperparathyroidism. We now investigate whether this pulsatile secretion of PTH in healthy men exhibits characteristics of nonlinear determinism. Our findings suggest that this is conceivable, although on the basis of presently available data and techniques, no proof can be established. Nevertheless, pulsatile secretion of PTH might be a first example of nonlinear deterministic dynamics in an apparently irregular hormonal rhythm in human physiology.

  8. Cellular and molecular effects for mutation induction in normal human cells irradiated with accelerated neon ions.

    PubMed

    Suzuki, Masao; Tsuruoka, Chizuru; Kanai, Tatsuaki; Kato, Takeshi; Yatagai, Fumio; Watanabe, Masami

    2006-02-22

    We investigated the linear energy transfer (LET) dependence of mutation induction on the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus in normal human fibroblast-like cells irradiated with accelerated neon-ion beams. The cells were irradiated with neon-ion beams at various LETs ranging from 63 to 335 keV/microm. Neon-ion beams were accelerated by the Riken Ring Cyclotron at the Institute of Physical and Chemical Research in Japan. Mutation induction at the HPRT locus was detected to measure 6-thioguanine-resistant clones. The mutation spectrum of the deletion pattern of exons of mutants was analyzed using the multiplex polymerase chain reaction (PCR). The dose-response curves increased steeply up to 0.5 Gy and leveled off or decreased between 0.5 and 1.0 Gy, compared to the response to (137)Cs gamma-rays. The mutation frequency increased up to 105 keV/microm and then there was a downward trend with increasing LET values. The deletion pattern of exons was non-specific. About 75-100% of the mutants produced using LETs ranging from 63 to 335 keV/mum showed all or partial deletions of exons, while among gamma-ray-induced mutants 30% showed no deletions, 30% partial deletions and 40% complete deletions. These results suggested that the dose-response curves of neon-ion-induced mutations were dependent upon LET values, but the deletion pattern of DNA was not.

  9. Reference genes for normalization of gene expression studies in human osteoarthritic articular cartilage

    PubMed Central

    Pombo-Suarez, Manuel; Calaza, Manuel; Gomez-Reino, Juan J; Gonzalez, Antonio

    2008-01-01

    Background Assessment of gene expression is an important component of osteoarthritis (OA) research, greatly improved by the development of quantitative real-time PCR (qPCR). This technique requires normalization for precise results, yet no suitable reference genes have been identified in human articular cartilage. We have examined ten well-known reference genes to determine the most adequate for this application. Results Analyses of expression stability in cartilage from 10 patients with hip OA, 8 patients with knee OA and 10 controls without OA were done with classical statistical tests and the software programs geNorm and NormFinder. Results from the three methods of analysis were broadly concordant. Some of the commonly used reference genes, GAPDH, ACTB and 18S RNA, performed poorly in our analysis. In contrast, the rarely used TBP, RPL13A and B2M genes were the best. It was necessary to use together several of these three genes to obtain the best results. The specific combination depended, to some extent, on the type of samples being compared. Conclusion Our results provide a satisfactory set of previously unused reference genes for qPCR in hip and knee OA This confirms the need to evaluate the suitability of reference genes in every tissue and experimental situation before starting the quantitative assessment of gene expression by qPCR. PMID:18226276

  10. Cytotoxicity evaluation of biodegradable Zn-3Mg alloy toward normal human osteoblast cells.

    PubMed

    Murni, N S; Dambatta, M S; Yeap, S K; Froemming, G R A; Hermawan, H

    2015-04-01

    The recent proposal of using Zn-based alloys for biodegradable implants was not supported with sufficient toxicity data. This work, for the first time, presents a thorough cytotoxicity evaluation of Zn-3Mg alloy for biodegradable bone implants. Normal human osteoblast cells were exposed to the alloy's extract and three main cell-material interaction parameters: cell health, functionality and inflammatory response, were evaluated. Results showed that at the concentration of 0.75mg/ml alloy extract, cell viability was reduced by ~50% through an induction of apoptosis at day 1; however, cells were able to recover at days 3 and 7. Cytoskeletal changes were observed but without any significant DNA damage. The downregulation of alkaline phosphatase protein levels did not significantly affect the mineralization process of the cells. Significant differences of cyclooxygenase-2 and prostaglandin E2 inflammatory biomarkers were noticed, but not interleukin 1-beta, indicating that the cells underwent a healing process after exposure to the alloy. Detailed analysis on the cell-material interaction is further discussed in this paper.

  11. Ultraviolet radiation acts as an independent mitogen for normal human melanocytes in culture

    SciTech Connect

    Libow, L.F.; Scheide, S.; DeLeo, V.A.

    1988-01-01

    Identification of growth factors for normal human melanocytes has been significantly aided by the recent development of in vitro culture systems for this cell. Utilizing such a system, we studied the effect of ultraviolet radiation (UVR) on both melanocyte growth and melanization by incorporation of 3H-thymidine and 3H-L-dihydroxyphenylalanine (3H-DOPA), respectively. 3H-thymidine incorporation was found to be significantly stimulated during the first 24 h following a single irradiation. 3H-DOPA incorporation was stimulated after a delay of 2 days postirradiation. Whereas UVR has long been known to induce melanocyte proliferation in vivo, these studies show that UVR can act as a mitogenic stimulus for this cell independent of the cutaneous environment. UVR can thus be added to a growing list of growth factors for epidermal pigment cells and is the only physical agent conclusively shown to act as a mitogen. Included in this list are substances that act via stimulation of the CAMP-kinase or protein kinase systems such as cholera toxin and phorbol esters. UVR is postulated to induce melanocyte proliferation by modulation of these second messenger pathways. With recent evidence linking growth factors, oncogenes and malignant transformation, this study supports the association between UVR exposure and the development of malignant melanoma, and suggests mechanisms whereby UVR may contribute to malignant transformation of this cell.

  12. Bioactivation, protein haptenation, and toxicity of sulfamethoxazole and dapsone in normal human dermal fibroblasts

    SciTech Connect

    Bhaiya, Payal; Roychowdhury, Sanjoy; Vyas, Piyush M.; Doll, Mark A.; Hein, David W.; Svensson, Craig K. . E-mail: craig-svensson@uiowa.edu

    2006-09-01

    Cutaneous drug reactions (CDRs) associated with sulfonamides are believed to be mediated through the formation of reactive metabolites that result in cellular toxicity and protein haptenation. We evaluated the bioactivation and toxicity of sulfamethoxazole (SMX) and dapsone (DDS) in normal human dermal fibroblasts (NHDF). Incubation of cells with DDS or its metabolite (D-NOH) resulted in protein haptenation readily detected by confocal microscopy and ELISA. While the metabolite of SMX (S-NOH) haptenated intracellular proteins, adducts were not evident in incubations with SMX. Cells expressed abundant N-acetyltransferase-1 (NAT1) mRNA and activity, but little NAT2 mRNA or activity. Neither NAT1 nor NAT2 protein was detected. Incubation of NHDF with S-NOH or D-NOH increased reactive oxygen species formation and reduced glutathione content. NHDF were less susceptible to the cytotoxic effect of S-NOH and D-NOH than are keratinocytes. Our studies provide the novel observation that NHDF are able to acetylate both arylamine compounds and bioactivate the sulfone DDS, giving rise to haptenated proteins. The reactive metabolites of SMX and DDS also provoke oxidative stress in these cells in a time- and concentration-dependent fashion. Further work is needed to determine the role of the observed toxicity in mediating CDRs observed with these agents.

  13. p16(INK4a) -mediated suppression of telomerase in normal and malignant human breast cells.

    PubMed

    Bazarov, Alexey V; Van Sluis, Marjolein; Hines, William C; Bassett, Ekaterina; Beliveau, Alain; Campeau, Eric; Mukhopadhyay, Rituparna; Lee, Won Jae; Melodyev, Sonya; Zaslavsky, Yuri; Lee, Leonard; Rodier, Francis; Chicas, Agustin; Lowe, Scott W; Benhattar, Jean; Ren, Bing; Campisi, Judith; Yaswen, Paul

    2010-10-01

    The cyclin-dependent kinase inhibitor p16(INK4a) (CDKN2A) is an important tumor suppressor gene frequently inactivated in human tumors. p16 suppresses the development of cancer by triggering an irreversible arrest of cell proliferation termed cellular senescence. Here, we describe another anti-oncogenic function of p16 in addition to its ability to halt cell cycle progression. We show that transient expression of p16 stably represses the hTERT gene, encoding the catalytic subunit of telomerase, in both normal and malignant breast epithelial cells. Short-term p16 expression increases the amount of histone H3 trimethylated on lysine 27 (H3K27) bound to the hTERT promoter, resulting in transcriptional silencing, likely mediated by polycomb complexes. Our results indicate that transient p16 exposure may prevent malignant progression in dividing cells by irreversible repression of genes, such as hTERT, whose activity is necessary for extensive self-renewal.

  14. Quantification and Characterization of UVB-Induced Mitochondrial Fragmentation in Normal Primary Human Keratinocytes

    PubMed Central

    Jugé, Romain; Breugnot, Josselin; Da Silva, Célia; Bordes, Sylvie; Closs, Brigitte; Aouacheria, Abdel

    2016-01-01

    UV irradiation is a major environmental factor causing skin dryness, aging and cancer. UVB in particular triggers cumulative DNA damage, oxidative stress and mitochondrial dysfunction. The objective of our study was to provide both qualitative and quantitative analysis of how mitochondria respond to UVB irradiation in normal human epidermal keratinocytes (NHEK) of healthy donors, with the rationale that monitoring mitochondrial shape will give an indication of cell population fitness and enable the screening of bioactive agents with UVB-protective properties. Our results show that NHEK undergo dose-dependent mitochondrial fragmentation after exposure to UVB. In order to obtain a quantitative measure of this phenomenon, we implemented a novel tool for automated quantification of mitochondrial morphology in live cells based on confocal microscopy and computational calculations of mitochondrial shape descriptors. This method was used to substantiate the effects on mitochondrial morphology of UVB irradiation and of knocking-down the mitochondrial fission-mediating GTPase Dynamin-related protein 1 (DRP1). Our data further indicate that all the major mitochondrial dynamic proteins are expressed in NHEK but that their level changes were stronger after mitochondrial uncoupler treatment than following UVB irradiation or DRP1 knock-down. Our system and procedures might be of interest for the identification of cosmetic or dermatologic UVB-protective agents. PMID:27731355

  15. Oxidation-induced calcium-dependent dehydration of normal human red blood cells.

    PubMed

    Shcherbachenko, Irina M; Lisovskaya, Irina L; Tikhonov, Vladimir P

    2007-05-01

    Phenazine-methosulphate (PMS) is a strong oxidant that induces reactive oxygen species (ROS) formation in cells. Though it has been shown that PMS increases the red blood cell (RBC) membrane permeability to K(+), the hypotheses on the mechanism of PMS-induced effects are contradictory and there are no data on volume changes induced by this oxidant. Therefore, the influence of the PMS + ascorbate oxidative system on the volume of normal human RBCs was studied. In a Ca(2 + )-containing medium, PMS + ascorbate caused dehydration (shrinking) of RBCs judged by: (1) changes in the density and osmotic resistance distributions of RBCs, and (2) a decrease in their low-angle scattering assessed by FACS analysis. The dehydration resulted from activation of the Gardos channels, was PMS and ascorbate concentration-dependent, was associated with broadening of the density and osmotic resistance distributions of the RBCs, and decreased in the presence of the taxifolin and rutin antioxidants. These findings contribute to a better understanding of the physiology and pathology of oxidatively-modified RBCs and may be of practical significance in estimating the antioxidant activity of various substances.

  16. Molecular Mechanisms of Malignant Transformation by Low Dose Cadmium in Normal Human Bronchial Epithelial Cells

    PubMed Central

    Kluz, Thomas; Cohen, Lisa; Shen, Steven S.; Costa, Max

    2016-01-01

    Cadmium is a carcinogenic metal, the mechanisms of which are not fully understood. In this study, human bronchial epithelial cells were transformed with sub-toxic doses of cadmium (0.01, 0.05, and 0.1 μM) and transformed clones were characterized for gene expression changes using RNA-seq, as well as other molecular measurements. 440 genes were upregulated and 47 genes were downregulated in cadmium clones relative to control clones over 1.25-fold. Upregulated genes were associated mostly with gene ontology terms related to embryonic development, immune response, and cell movement, while downregulated genes were associated with RNA metabolism and regulation of transcription. Several embryonic genes were upregulated, including the transcription regulator SATB2. SATB2 is critical for normal skeletal development and has roles in gene expression regulation and chromatin remodeling. Small hairpin RNA knockdown of SATB2 significantly inhibited growth in soft agar, indicating its potential as a driver of metal-induced carcinogenesis. An increase in oxidative stress and autophagy was observed in cadmium clones. In addition, the DNA repair protein O6-methylguanine-DNA-methyltransferase was depleted by transformation with cadmium. MGMT loss caused significant decrease in cell viability after treatment with the alkylating agent temozolomide, demonstrating diminished capacity to repair such damage. Results reveal various mechanisms of cadmium-induced malignant transformation in BEAS-2B cells including upregulation of SATB2, downregulation of MGMT, and increased oxidative stress. PMID:27186882

  17. P16INK4a MEDIATED SUPPRESSION OF TELOMERASE IN NORMAL AND MALIGNANT HUMAN BREAST CELLS

    PubMed Central

    Bazarov, Alexey V.; van Sluis, Marjolein; Hines, Curtis; Bassett, Ekaterina; Beliveau, Alain; Campeau, Eric; Mukhopadhyay, Rituparna; Lee, Won Jae; Melodyev, Sonya; Zaslavsky, Yuri; Lee, Leonard; Rodier, Francis; Chicas, Agustin; Lowe, Scott W.; Benhattar, Jean; Ren, Bing; Campisi, Judith; Yaswen, Paul

    2010-01-01

    Summary The cyclin-dependent kinase inhibitor p16INK4a (CDKN2A) is an important tumor-suppressor gene frequently inactivated in human tumors. p16 suppresses the development of cancer by triggering an irreversible arrest of cell proliferation termed cellular senescence. Here, we describe another anti-oncogenic function of p16 in addition to its ability to halt cell cycle progression. We show that transient expression of p16 stably represses the hTERT gene, encoding the catalytic subunit of telomerase, in both normal and malignant breast epithelial cells. Short-term p16 expression increases the amount of histone H3 trimethylated on lysine 27 (H3K27) bound to the hTERT promoter, resulting in transcriptional silencing, likely mediated by polycomb complexes. Our results indicate that transient p16 exposure may prevent malignant progression in dividing cells by irreversible repression of genes, such as hTERT, whose activity is necessary for extensive self-renewal. PMID:20569236

  18. Preliminary micro-Raman images of normal and malignant human skin cells

    NASA Astrophysics Data System (ADS)

    Short, Michael A.; Lui, Harvey; McLean, David I.; Zeng, Haishan; Chen, Michael X.

    2006-02-01

    Micro-Raman spectroscopy covering a frequency range from 200 to 4000 cm -1 was used to image human skin melanocytes and keratinocytes with a spatial resolution of 0.5 μm. The cells were either cultivated on glass microscope slides or were located within thin sections of skin biopsies mounted on low fluorescence BaF II. A commercially available system was used to obtain the spectra utilizing a x100 long working distance objective with a numerical aperture of 0.8, and a cooled CCD. Both 633 and 515 nm excitations were tried, although the latter proved to be more effcient at producing Raman emission mostly due to the 1/λ 4 dependence in light scattering. Fluorescence emission from the cells was surprisingly low. The excitation power at the sample was kept below about 2 mW to avoid damaging the cells; this was the limiting factor on how quickly a Raman image could be obtained. Despite this diffculty we were able to obtain Raman images with rich information about the spectroscopic and structural features within the cytoplasm and cell nuclei. Differences were observed between the Raman images of normal and malignant cells. Spectra from purified DNA, RNA, lipids, proteins and melanin were obtained and these spectra were compared with the skin cell spectra with the aim of understanding how they are distributed over a cell and how the distribution changes between different cells.

  19. Effect of norfloxacin and moxifloxacin on melanin synthesis and antioxidant enzymes activity in normal human melanocytes.

    PubMed

    Beberok, Artur; Wrześniok, Dorota; Otręba, Michał; Miliński, Maciej; Rok, Jakub; Buszman, Ewa

    2015-03-01

    Fluoroquinolone antibiotics provide broad-spectrum coverage for a number of infectious diseases, including respiratory as well as urinary tract infections. One of the important adverse effects of these drugs is phototoxicity which introduces a serious limitation to their use. To gain insight the molecular mechanisms underlying the fluoroquinolones-induced phototoxic side effects, the impact of two fluoroquinolone derivatives with different phototoxic potential, norfloxacin and moxifloxacin, on melanogenesis and antioxidant enzymes activity in normal human melanocytes HEMa-LP was determined. Both drugs induced concentration-dependent loss in melanocytes viability. The value of EC50 for these drugs was found to be 0.5 mM. Norfloxacin and moxifloxacin suppressed melanin biosynthesis; antibiotics were shown to inhibit cellular tyrosinase activity and to reduce melanin content in melanocytes. When comparing the both analyzed fluoroquinolones, it was observed that norfloxacin possesses greater inhibitory effect on tyrosinase activity in melanocytes than moxifloxacin. The extent of oxidative stress in cells was assessed by measuring the activity of antioxidant enzymes: SOD, CAT, and GPx. It was observed that norfloxacin caused higher depletion of antioxidant status in melanocytes when compared with moxifloxacin. The obtained results give a new insight into the mechanisms of fluoroquinolones toxicity directed to pigmented tissues. Moreover, the presented differences in modulation of biochemical processes in melanocytes may be an explanation for various phototoxic activities of the analyzed fluoroquinolone derivatives in vivo.

  20. Determination of oxidation state of iron in normal and pathologically altered human aortic valves

    NASA Astrophysics Data System (ADS)

    Czapla-Masztafiak, J.; Lis, G. J.; Gajda, M.; Jasek, E.; Czubek, U.; Bolechała, F.; Borca, C.; Kwiatek, W. M.

    2015-12-01

    In order to investigate changes in chemical state of iron in normal and pathologically altered human aortic valves X-ray absorption spectroscopy was applied. Since Fe is suspected to play detrimental role in aortic valve stenosis pathogenesis the oxidation state of this element has been determined. The experimental material consisted of 10 μm sections of valves excised during routine surgery and from autopsies. The experiment was performed at the MicroXAS beamline of the SLS synchrotron facility in Villigen (Switzerland). The Fe K-edge XANES spectra obtained from tissue samples were carefully analyzed and compared with the spectra of reference compounds containing iron in various chemical structures. The analysis of absorption edge position and shape of the spectra revealed that both chemical forms of iron are presented in valve tissue but Fe3+ is the predominant form. Small shift of the absorption edge toward higher energy in the spectra from stenotic valve samples indicates higher content of the Fe3+ form in pathological tissue. Such a phenomenon suggests the role of Fenton reaction and reactive oxygen species in the etiology of aortic valve stenosis. The comparison of pre-edge regions of XANES spectra for control and stenotic valve tissue confirmed no differences in local symmetry or spin state of iron in analyzed samples.

  1. LET and ion-species dependence for cell killing and mutation induction in normal human fibroblasts.

    PubMed

    Tsuruoka, Chizuru; Suzuki, Masao; Fujitaka, Kazunobu

    2003-10-01

    We have been studying LET and ion species dependence of RBE values in cell killing and mutation induction. Normal human skin fibroblasts were irradiated with heavy-ion beams such as carbon (290 Mev/u and 135 Mev/u), neon (230 Mev/u and 400 Mev/u), silicon (490 Mev/u) and iron (500 Mev/u) ion beams, generated by Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological Sciences (NIRS). Cell killing effect was detected as reproductive cell death using a colony formation assay. Mutation induction in hprt locus was detected to measure 6-thioguanine resistant colonies. The RBE-LET curves of cell killing and mutation induction were different each ion beam. So, we plotted RBE for cell killing and mutation induction as function of Z*2/beta2 instead of LET. RBE-Z*2/beta2 curves of cell killing indicated that the discrepancy of RBE-LET curves was reconciled each ion species. But RBE-Z*2/beta2 curves of mutation induction didn't corresponded between carbon- and silicon-ion beams. These results suggested that different biological endpoints may be suitable for different physical parameter, which represent the track structure of energy deposition of ion beams.

  2. Interactions of Bacillus licheniformis ATCC 10716 and normal flora of human skin.

    PubMed

    Bibel, D J; Smiljanic, R J; Lovell, D J

    1978-06-01

    To determine whether antibiotic production might be ecologically advantageous in the survival of Bacillus species on human skin, we applied spores of a bacitracin-producing strain of Bacillus licheniformis (ATCC 10716) to the forearms of 11 volunteers. Three additional strains of B. licheniformis which did not synthesize antibiotics, including a mutant of ATCC 10716, were used in subsequent control trials. Samples of flora were taken from inoculated and control (opposite forearm) sites during the colonization period, generally 3 weeks. Although population densities were unaltered, changes in the carriage, composition, and bacitracin sensitivity of resident flora were related with the presence of ATCC 10716 only, which suggests that microbial interactions are important in bacillus colonization and in maintenance of normal flora. Interactions were examined in vitro by comparing growth curves of representative skin bacteria, including isolates of Staphylococcus epidermidis, Staphylococcus saprophyticus, Micrococcus luteus, and a large-colony diphtheroid, grown individually, in mixed culture with each other, and together in presence of each test strain of B. licheniformis. We observed some diminution of growth of M. luteus and the diphtheroid in the first mixed culture, and the diphtheroid was completely retarded in common culture with ATCC 10716. Lesser antibiotic effects were seen on the cocci, whose rank of sensitivity was similar to that in vivo. The growth of the diphtheroid was enhanced in mixed culture with those strains of bacilli which lack antibiotic activity.

  3. Unstable Chromosome Aberrations Do Not Accumulate in Normal Human Fibroblast after Fractionated X-Irradiation

    PubMed Central

    Ojima, Mitsuaki; Ito, Maki; Suzuki, Keiji; Kai, Michiaki

    2015-01-01

    We determined the frequencies of dicentric chromosomes per cell in non-dividing confluent normal human fibroblasts (MRC-5) irradiated with a single 1 Gy dose or a fractionated 1 Gy dose (10X0.1 Gy, 5X0.2 Gy, and 2X0.5 Gy). The interval between fractions was between 1 min to 1440 min. After the completion of X-irradiation, the cells were incubated for 24 hours before re-plating at a low density. Then, demecolcine was administrated at 6 hours, and the first mitotic cells were collected for 42 hours. Our study demonstrated that frequencies of dicentric chromosomes in cells irradiated with a 1 Gy dose at different fractions were significantly reduced if the fraction interval was increased from 1 min to 5 min (p<0.05, χ2-test). Further increasing the fraction interval from 5 up to 1440 min did not significantly affect the frequency of dicentric chromosomes. Since misrejoining of two independent chromosome breaks introduced in close proximity gives rise to dicentric chromosome, our results indicated that such circumstances might be quite infrequent in cells exposed to fractionated X-irradiation with prolonged fraction intervals. Our findings should contribute to improve current estimation of cancer risk from chronic low-dose-rate exposure, or intermittent exposure of low-dose radiation by medical exposure. PMID:25723489

  4. Normal level of sepsis-associated phenylcarboxylic acids in human serum.

    PubMed

    Beloborodova, N V; Moroz, V V; Osipov, A A; Bedova, A Yu; Olenin, A Yu; Getsina, M L; Karpova, O V; Olenina, E G

    2015-03-01

    Previous studies showed that large amounts of phenylcarboxylic acids (PhCAs) are accumulated in a septic patient's blood due to increased endogenous and microbial phenylalanine and tyrosine biotransformation. Frequently, biochemical aromatic amino acid transformation into PhCAs is considered functionally insignificant for people without monogenetic hereditary diseases. The blood of healthy people contains the same PhCAs that are typical for septic patients as shown in this paper. The overall serum PhCAs level was 6 µM on average as measured by gas chromatography with flame ionization detection. This level is a stable biochemical parameter indicating the normal metabolism of aromatic amino acids. The concentrations of PhCAs in the metabolic profile of healthy people are distributed as follows: phenylacetic ≈ p-hydroxyphenyllactic > p-hydroxyphenylacetic > phenyllactic ≈ phenylpropionic > benzoic. We conclude that maintaining of stable PhCAs level in the serum is provided as the result of integration of human endogenous metabolic pathways and microbiota.

  5. Extensive demethylation of normally hypermethylated CpG islands occurs in human atherosclerotic arteries.

    PubMed

    Castillo-Díaz, Silvia A; Garay-Sevilla, María E; Hernández-González, Martha A; Solís-Martínez, Martha O; Zaina, Silvio

    2010-11-01

    Global DNA hypomethylation potentially leading to pro-atherogenic gene expression occurs in atherosclerotic lesions. However, limited information is available on the genomic location of hypomethylated sequences. We present a microarray-based survey of the methylation status of CpG islands (CGIs) in 45 human atherosclerotic arteries and 16 controls. Data from 10,367 CGIs revealed that a subset (151 or 1.4%) of these was hypermethylated in control arteries. The vast majority (142 or 94%) of this CGI subset was found to be unmethylated or partially methylated in atherosclerotic tissue, while only 17 of the normally unmethylated CGIs were hypermethylated in the diseased tissue. The most common functional classes among annotated genes adjacent to or containing differentially methylated CGIs, were transcription (23%) and signalling factors (16%). The former included HOX members, PROX1, NOTCH1 and FOXP1, which are known to regulate key steps of atherogenesis. Expression analysis revealed differential expression of all CGI-associated genes analysed. Sequence analysis identified novel DNA motifs with regulatory potential, associated with differentially methylated CGIs. This study is the first large-scale analysis of DNA methylation in atherosclerosis. Our data suggest that aberrant DNA methylation in atherosclerosis affects the transcription of critical regulatory genes for the induction of a pro-atherogenic cellular phenotype.

  6. Recombinant DNA derived monomeric insulin analogue: comparison with soluble human insulin in normal subjects.

    PubMed Central

    Vora, J. P.; Owens, D. R.; Dolben, J.; Atiea, J. A.; Dean, J. D.; Kang, S.; Burch, A.; Brange, J.

    1988-01-01

    OBJECTIVE--To compare the rate of absorption from subcutaneous tissue and the resulting hypoglycaemic effect of iodine-125 labelled soluble human insulin and a monomeric insulin analogue derived by recombinant DNA technology. DESIGN--Single blind randomised comparison of equimolar doses of 125I labelled soluble human insulin and insulin analogue. SETTING--Study in normal people at a diabetes research unit and a university department of medical physics. SUBJECTS--Seven healthy male volunteers aged 20-39 not receiving any other drugs. INTERVENTIONS--After an overnight fast and a basal period of one hour two doses (0.05 and 0.1 U/kg) of 125I labelled soluble human insulin and insulin analogue were injected subcutaneously into the anterior abdominal wall on four separate days. END POINT--To find a fast acting insulin for meal related requirements in insulin dependent diabetics. MEASUREMENTS and main results--Residual radioactivity at the injection site was measured continuously for the first two hours after injection of the 125I labelled preparations and thereafter for five minutes simultaneously with blood sampling. Frequent venous blood samples were obtained over six hours for determination of plasma immunoreactive insulin, insulin analogue, glucose, and glucagon values. Time to 50% of initial radioactivity at the injection site for the insulin analogue compared with soluble insulin was 61 v 135 minutes (p less than 0.05) with 0.05 U/kg and 67 v 145 minutes (p less than 0.001) with 0.1 U/kg. Concentrations in plasma increased faster after the insulin analogue compared with soluble insulin, resulting in higher plasma concentrations between 10 and 150 minutes (0.001 less than p less than 0.05) after 0.05 U/kg and between 40 and 360 minutes (0.001 less than p less than 0.05) after 0.1 U/kg. The hypoglycaemic response to insulin analogue was a plasma glucose nadir at 60 minutes with both doses compared with 90 and 120 minutes with soluble insulin at 0.5 and 0.1 U

  7. Mössbauer spectroscopic study of the forms of iron in normal human liver and spleen tissue

    NASA Astrophysics Data System (ADS)

    Chua-Anusorn, W.; Pierre, T. G. St.; Webb, J.; Macey, D. J.; Yansukon, P.; Pootrakul, P.

    1994-12-01

    Mössbauer spectra of 12 normal human spleen and 12 normal human liver samples ( post mortem) from Australia and Thailand have been recorded at 78 K. The spectra show the presence of iron in the form of ferrihydrite, together with some deoxyhemoglobin and methemoglobin in some samples. The spectra were used in conjunction with elemental analysis to calculate the non-heme iron concentrations in the tissues. The mean non-heme iron concentration in the Thai livers was significantly less than that for the Australian samples. The goethite-like form of hemosiderin that has been observed in some pathological tissues was not detected.

  8. AFM stiffness nanotomography of normal, metaplastic and dysplastic human esophageal cells

    NASA Astrophysics Data System (ADS)

    Fuhrmann, A.; Staunton, J. R.; Nandakumar, V.; Banyai, N.; Davies, P. C. W.; Ros, R.

    2011-02-01

    The mechanical stiffness of individual cells is important in tissue homeostasis, cell growth, division and motility, and the epithelial-mesenchymal transition in the initiation of cancer. In this work, a normal squamous cell line (EPC2) and metaplastic (CP-A) as well as dysplastic (CP-D) Barrett's Esophagus columnar cell lines are studied as a model of pre-neoplastic progression in the human esophagus. We used the combination of an atomic force microscope (AFM) with a scanning confocal fluorescence lifetime imaging microscope to study the mechanical properties of single adherent cells. Sixty four force indentation curves were taken over the nucleus of each cell in an 8 × 8 grid pattern. Analyzing the force indentation curves, indentation depth-dependent Young's moduli were found for all cell lines. Stiffness tomograms demonstrate distinct differences between the mechanical properties of the studied cell lines. Comparing the stiffness for indentation forces of 1 nN, most probable Young's moduli were calculated to 4.7 kPa for EPC2 (n = 18 cells), 3.1 kPa for CP-A (n = 10) and 2.6 kPa for CP-D (n = 19). We also tested the influence of nuclei and nucleoli staining organic dyes on the mechanical properties of the cells. For stained EPC2 cells (n = 5), significant stiffening was found (9.9 kPa), while CP-A cells (n = 5) showed no clear trend (2.9 kPa) and a slight softening was observed (2.1 kPa) in the case of CP-D cells (n = 16). Some force-indentation curves show non-monotonic discontinuities with segments of negative slope, resembling a sawtooth pattern. We found the incidence of these 'breakthrough events' to be highest in the dysplastic CP-D cells, intermediate in the metaplastic CP-A cells and lowest in the normal EPC2 cells. This observation suggests that the microscopic explanation for the increased compliance of cancerous and pre-cancerous cells may lie in their susceptibility to 'crumble and yield' rather than their ability to 'bend and flex'.

  9. Heterogeneous nuclear expression of the promyelocytic leukemia (PML) protein in normal and neoplastic human tissues.

    PubMed Central

    Gambacorta, M.; Flenghi, L.; Fagioli, M.; Pileri, S.; Leoncini, L.; Bigerna, B.; Pacini, R.; Tanci, L. N.; Pasqualucci, L.; Ascani, S.; Mencarelli, A.; Liso, A.; Pelicci, P. G.; Falini, B.

    1996-01-01

    The RING-finger promyelocytic leukemia (PML) protein is the product of the PML gene that fuses with the retinoic acid receptor-alpha gene in the t(15; 17) translocation of acute promyelocytic leukemia. Wild-type PML localizes in the nucleus with a typical speckled pattern that is a consequence of the concentration of the protein within discrete subnuclear domains known as nuclear bodies. Delocalization of PML from nuclear bodies has been documented in acute promyelocytic leukemia cells and suggested to contribute to leukemogenesis. In an attempt to get new insights into the function of the wild-type PML protein and to investigate whether it displays an altered expression pattern in neoplasms other than acute promyelocytic leukemia, we stained a large number of normal and neoplastic human tissues with a new murine monoclonal antibody (PG-M3) directed against the amino-terminal region of PML. As the PG-M3 epitope is partially resistant to fixatives, only cells that overexpress PML are detected by the antibody in microwave-heated paraffin sections. Among normal tissues, PML was characteristically up-regulated in activated epithelioid histiocytes and fibroblasts in a variety of pathological conditions, columnar epithelium in small active thyroid follicles, well differentiated foamy cells in the center of sebaceous glands, and hypersecretory endometria (Arias-Stella). Interferons, the PML of which is a primary target gene, and estrogens are likely to represent some of the cytokines and/or hormones that may be involved in the up-regulation of PML under these circumstances. In keeping with this concept, we found that PML is frequently overexpressed in Hodgkin and Reed-Sternberg cells of Hodgkin's disease, a tumor of cytokine-producing cells. Among solid tumors, overexpression of PML was frequently found in carcinomas of larynx and thyroid (papillary), epithelial thymomas, and Kaposi's sarcoma, whereas carcinomas of the lung, thyroid (follicular), breast, and colon were

  10. Neuronal plasticity of trigeminal ganglia in mice following nerve injury

    PubMed Central

    Lynds, Randi; Lyu, Chuang; Lyu, Gong-Wei; Shi, Xie-Qi; Rosén, Annika; Mustafa, Kamal; Shi, Tie-Jun Sten

    2017-01-01

    Background Nerve injury may induce neuropathic pain. In studying the mechanisms of orofacial neuropathic pain, attention has been paid to the plastic changes that occur in the trigeminal ganglia (TGs) and nucleus in response to an injury of the trigeminal nerve branches. Previous studies have explored the impact of sciatic nerve injury on dorsal root ganglia (DRGs) and it has shown dramatic changes in the expression of multiple biomarkers. In large, the changes in biomarker expression in TGs after trigeminal nerve injury are similar to that in DRGs after sciatic nerve injury. However, important differences exist. Therefore, there is a need to study the plasticity of biomarkers in TGs after nerve injury in the context of the development of neuropathic pain-like behaviors. Aim The aim of this study was to investigate the plasticity of biomarkers associated with chronic persistent pain in TGs after trigeminal nerve injury. Materials and methods To mimic the chronic nature of the disorder, we used an intraoral procedure to access the infraorbital nerve (ION) and induced a nerve injury in mice. Immunohistochemistry and quantification were used for revealing the expression level of each biomarker in TGs after nerve injury. Results Two weeks after partial ION injury, immunohistochemistry results showed strongly upregulated expressions of activating transcription factor 3 and neuropeptide Y (NPY) in the ipsilateral TGs. Microglial cells were also activated after nerve injury. In regard to positive neuronal profile counting, however, no significant difference in expression was observed in galanin, substance P, calcitonin gene-related peptide, neuronal nitric oxide synthase, phosphorylated AKT, or P2X3 in ipsilateral TGs when compared to contralateral TGs. Conclusion In this study, the expression and regulation of biomarkers in TGs have been observed in response to trigeminal nerve injury. Our results suggest that NPY and Iba1 might play crucial roles in the pathogenesis of

  11. Ocular inflammation induces trigeminal pain, peripheral and central neuroinflammatory mechanisms.

    PubMed

    Launay, Pierre-Serge; Reboussin, Elodie; Liang, Hong; Kessal, Karima; Godefroy, David; Rostene, William; Sahel, Jose-Alain; Baudouin, Christophe; Melik Parsadaniantz, Stéphane; Reaux Le Goazigo, Annabelle

    2016-04-01

    Ocular surface diseases are among the most frequent ocular pathologies, with prevalence ranging from 20% of the general population. In addition, ocular pain following corneal injury is frequently observed in clinic. The aim of the study was to characterize the peripheral and central neuroinflammatory process in the trigeminal pathways in response to cornea alteration induced by chronic topical instillations of 0.2% benzalkonium chloride (BAC) in male C57BL/6J mice. In vitro BAC induced neurotoxicity and increases neuronal (FOS, ATF3) and pro-inflammatory (IL-6) markers in primary mouse trigeminal ganglion culture. BAC-treated mice exhibited 7days after the treatment reduced aqueous tear production and increased inflammatory cell infiltration in the cornea. Hypertonic saline-evoked eye wipe behavior was enhanced in BAC-treated animals that exhibited increased FOS, ATF3 and Iba1 immunoreactivity in the trigeminal ganglion. Ocular inflammation is associated with a significant increase in IL-6 and TNF-α mRNA expression in the trigeminal ganglion. We reported a strong increase in FOS and Iba1 positive cells in particular in the sensory trigeminal complex at the ipsilateral interpolaris/caudalis (Vi/Vc) transition and Vc/upper cervical cord (Vc/C1) regions. In addition, activated microglial cells were tightly wrapped around activated FOS neurons in both regions and phosphorylated p38 mitogen-activated protein kinase was markedly enhanced specifically in microglial cells during ocular inflammation. Similar data were obtained in the facial motor nucleus. These neuroanatomical data correlated with the increase in mRNA expression of pro-inflammatory (TNF-α, IL-6, CCL2) and neuronal (FOS and ATF3) markers. Interestingly, the suppression of corneal inflammation 10days following the end of BAC treatment resulted in a marked attenuation of peripheral and central changes observed in pathological conditions. This study provides the first demonstration that corneal inflammation

  12. Revisiting vocal perception in non-human animals: a review of vowel discrimination, speaker voice recognition, and speaker normalization

    PubMed Central

    Kriengwatana, Buddhamas; Escudero, Paola; ten Cate, Carel

    2015-01-01

    The extent to which human speech perception evolved by taking advantage of predispositions and pre-existing features of vertebrate auditory and cognitive systems remains a central question in the evolution of speech. This paper reviews asymmetries in vowel perception, speaker voice recognition, and speaker normalization in non-human animals – topics that have not been thoroughly discussed in relation to the abilities of non-human animals, but are nonetheless important aspects of vocal perception. Throughout this paper we demonstrate that addressing these issues in non-human animals is relevant and worthwhile because many non-human animals must deal with similar issues in their natural environment. That is, they must also discriminate between similar-sounding vocalizations, determine signaler identity from vocalizations, and resolve signaler-dependent variation in vocalizations from conspecifics. Overall, we find that, although plausible, the current evidence is insufficiently strong to conclude that directional asymmetries in vowel perception are specific to humans, or that non-human animals can use voice characteristics to recognize human individuals. However, we do find some indication that non-human animals can normalize speaker differences. Accordingly, we identify avenues for future research that would greatly improve and advance our understanding of these topics. PMID:25628583

  13. Decision-making in classic trigeminal neuralgia concurrent with a pontine cavernous malformation: Causal or coincidental association?

    PubMed

    Parise, Maud; Acioly, Marcus André; Vincent, Maurice; Gasparetto, Emerson Leandro

    2015-01-01

    Trigeminal neuralgia is classically associated with neurovascular compression of the trigeminal nerve, at the root entry zone (REZ). However, patients are occasionally affected by intra-axial involvement of trigeminal sensory fibers caused by demyelinating diseases, strokes and, rarely, pontine cavernous malformations. We discuss the management strategies and decision-making process in a 55-year-old patient, affected by trigeminal neuralgia with 2 potential causative mechanisms: a neurovascular conflict at the trigeminal REZ and an ipsilateral cavernous malformation at the pontine nucleus of the trigeminal nerve.

  14. Evidence for multiple bone resorption-stimulating factors produced by normal human keratinocytes in culture.

    PubMed

    Fried, R M; Voelkel, E F; Rice, R H; Levine, L; Tashjian, A H

    1988-06-01

    Conditioned medium from cultured normal human foreskin keratinocytes enhanced the release of calcium from neonatal mouse calvaria in organ culture. Unfractionated keratinocyte-conditioned medium (KCM) stimulated bone resorption in a dose-dependent manner, but it did not increase the concentration of prostaglandin E2 (PGE2) in the bone culture medium until a maximal dose of KCM for resorption was used. Furthermore, inhibitors of PGE2 synthesis, indomethacin, ibuprofen, and piroxicam, did not inhibit KCM-induced calcium release. High concentrations of KCM increased cAMP production by calvaria in the presence of isobutylmethylxanthine, but the increase was small compared with that produced by a dose of bovine PTH that caused a similar level of bone resorption. The bone resorption-stimulating activity of KCM was not lost after incubation at 56 C for 60 min, but it was lost after heating at 100 C for 10 min. Fractionation of KCM by gel filtration chromatography revealed two distinct peaks of bone resorption-stimulating activity. One peak, KCMI, caused a significant increase in bone resorption at 2 micrograms protein/ml. KCMI did not increase medium PGE2, and inhibition of PGE2 synthesis in bone had no effect on KCMI-induced bone resorption. KCMI failed to increase cAMP production by human osteosarcoma SaOS-2 cells. Another peak, KCMII, caused a dose-dependent increase in bone resorption, and a significant increase in medium calcium was noted at a 20-fold lower concentration (0.1 microgram protein/ml) than with KCMI. In contrast to KCMI, the increase in bone resorption stimulated by KCMII was accompanied by a parallel increase in the production of PGE2, and inhibition of PGE2 synthesis completely inhibited the bone resorption-stimulating activity of KCMII. KCMII also caused an increase in cAMP production by SaOS-2 cells. We conclude that KCM contains at least two distinct bone resorption-stimulating factors, one of which acts via a PG-mediated mechanism and the other by

  15. Differential Effects of Lovastatin on Cisplatin Responses in Normal Human Mesothelial Cells versus Cancer Cells: Implication for Therapy

    PubMed Central

    Shi, Yandong; Felley-Bosco, Emanuela; Marti, Thomas M.; Stahel, Rolf A.

    2012-01-01

    The cancer killing efficacy of standard chemotherapeutic agents such as cisplatin (CDDP) is limited by their side effects to normal tissues. Therefore, research efforts optimizing the safety and efficacy of those agents are clinically relevant. We did screen for agents that specifically protect normal human mesothelial cells against CDDP without reducing the cancer cell killing efficacy. Lovastatin was identified from the screen. Lovastatin at a pharmacologically relevant concentration strongly arrested the proliferation of normal cells, whereas cancer cells were less affected. CDDP-induced DNA damage response was not activated and normal cells showed enhanced tolerance to CDDP when normal cells were treated with the combination of CDDP and lovastatin. We demonstrate that interfering with protein geranylgeranylation is involved in the lovastatin-mediated CDDP protective effect in normal cells. In contrast to normal cells, in cancer cells lovastatin did not change the CDDP-induced response, and cancer cells were not protected by lovastatin. Furthermore, lovastatin at the pharmacological relevant concentration per se induced DNA damage, oxidative stress and autophagy in cancer cells but not in normal mesothelial cells. Therefore, our data suggest that lovastatin has a potential to improve the therapeutic index of cisplatin-based therapy. PMID:23028957

  16. Effects of high-energy shockwaves on normal human fibroblasts in suspension.

    PubMed

    Kaulesar Johannes, E J; Sukul, D M; Bijma, A M; Mulder, P G

    1994-12-01

    To gain insight in the effects of shockwaves on human cells the relationship between the energy density and the number of shockwaves as well as their effect on suspensions of normal cells was studied. At energy densities of 0.37, 0.6, 0.78, and 1.20 mJ/mm2 fibroblasts were subjected to 50, 100, 250, 500, and 1,000 shockwaves. Each test was performed three times and one sample was used as control. A decrease in viability related to the logarithm of both the number (P = 0.0000) and the energy density (P = 0.001) of the shockwaves was statistically demonstrable 1 hr after the shockwave application. The energy density of the shockwaves has less influence on the viability than the number of applied shockwaves. Seeding of viable cells 1 hr after the shockwave application showed that the decrease in the 48-hr growth potential was statistically dependent of the number of applied shockwaves only (P = 0.0007). After 24 hr no difference in the 48-hr growth potential could be demonstrated between viable shockwave-treated cells and control cells. The literature as well as our own investigations in vitro and in vivo indicate that shockwaves have a logarithmic dose-dependent destructive effect on cells in suspension, but they also seem to have a dose-dependent stimulating influence on the healing process in damaged tissues. Due to the logarithmic relationship between the viability and both the number and energy density of the applied shockwaves it might be expected that even excessive numbers of high-energy-density shockwaves don't soon lead to total destruction of all cells in the suspension.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes

    SciTech Connect

    Vaziri, H.; Uchida, I.; Lan Wei; Harley, C.B. ); Schaechter, F.; Cohen, D. ); Xiaoming Zhu; Effros, R. )

    1993-04-01

    The telomere hypothesis of cellular aging proposes that loss of telomeric DNA (TTAGGG) from human chromosomes may ultimately cause cell-cycle exit during replicative senescence. Since lymphocytes have a limited replicative capacity and since blood cells were previously shown to lose telomeric DNA during aging in vivo, the authors wished to determine (a) whether accelerated telomere loss is associated with the premature immunosenescence of lymphocytes in individuals with Down syndrome (DS) and (b) whether telomeric DNA is also lost during aging of lymphocytes in vitro. To investigate the effects of aging and trisomy 21 on telomere loss in vivo, genomic DNA was isolated from peripheral blood lymphocytes of 140 individuals (age 0--107 years), including 21 DS patients (age 0--45 years). Digestion with restriction enzymes HinfI and RsaI generated terminal restriction fragments (TRFs), which were detected by Southern analysis using a telomere-specific probe ([sup 32]P-(C[sub 3]TA[sub 2])[sub 3]). The rate of telomere loss was calculated from the decrease in mean TRF length, as a function of donor age. DS patients showed a significantly higher rate of telomere loss with donor age (133 [+-] 15 bp/year) compared with age-matched controls (41 [+-] 7.7 bp/year) (P < .0005), suggesting that accelerated telomere loss is a biomarker of premature immunosenescence of DS patients and that it may play a role in this process. Telomere loss during aging in vitro was calculated for lymphocytes from four normal individuals, grown in culture for 10--30 population doublings. The rate of telomere loss was [approximately]120 bp/cell doubling, comparable to that seen in other somatic cells. Moreover, telomere lengths of lymphocytes from centenarians and from older DS patients were similar to those of senescent lymphocytes in culture, which suggests that replicative senescence could partially account for aging of the immune system in DS patients and in elderly individuals. 31 refs., 3 figs.

  18. Regulatory effects of heat on normal human melanocyte growth and melanogenesis: comparative study with UVB.

    PubMed

    Nakazawa, K; Sahuc, F; Damour, O; Collombel, C; Nakazawa, H

    1998-06-01

    Although energy-rich ultraviolet B (UVB) is considered to be primarily responsible for most of the effects associated with solar radiation, small energy recorded as heat appears to contribute to the biologic effects of solar radiation on the skin. We compared the effects of heat and UVB on normal human melanocyte functions. In monolayer culture the following was found. (i) Heat-treated melanocytes showed an increased dendricity and exhibited a larger cell body compared with nontreated melanocytes. (ii) After multiple treatments with UVB (20 mJ per cm2, 312 nm) or heat (42 degrees C for 1 h) for 3 d, melanocytes had a lower survival than nontreated melanocytes, but they resumed proliferation within 6 d in the same manner as seen in control. (iii) The expression levels of cell cycle regulators, p53 and p21 proteins, were increased after multiple treatments with UVB or heat. (iv) The tyrosinase (dopa-oxidase) activity per cell was increased after the multiple treatments with UVB or heat. (v) The number of dopa-positive melanocytes in coculture with keratinocytes in epithelial sheets was greatly increased by UVB or heat treatments. (vi) Similarly, the increased number of tyrosinase-related protein 1 positive melanocytes was seen in skin equivalents after UVB (100 mJ per cm2) or heat (42 degrees C for 1 h) treatments for 7 d. These results suggest that heat shares significant biologic activities with UVB in melanocyte functions. These results could be considered as one of the protective or adaptive responses of the skin pigmentary system to the environment.

  19. Fib420: a normal human variant of fibrinogen with two extended alpha chains.

    PubMed Central

    Fu, Y; Grieninger, G

    1994-01-01

    In fibrinogen, alpha E chains form a subpopulation of alpha subunits that are distinguished by a carboxyl extension homologous to the C termini of the other two constituent chains: beta and gamma. The molecular mass of alpha E is > 50% greater than that of the common alpha subunit, due in part to an extra 236 amino acids. These residues are encoded by exon VI, a recently discovered extension of the fibrinogen alpha gene. Additional mass is contributed by posttranslational processing, including N-glycosylation, which, based on experiments with the inhibitor tunicamycin, was found to account in large measure for alpha E migration on SDS/PAGE at approximately 110 kDa rather than at its calculated mass of 92,843 Da. An antibody specific for the exon VI-encoded domain of alpha E (anti-VI) and capable of recognizing alpha E-containing fibrinogen in both native and denatured form was generated using a recombinant protein as immunogen. Its use in Western blot analysis of fractions of normal human blood (plasma and preparations of fibrinogen) revealed a single, sharp, alpha E-containing band migrating behind the position of the broad, predominant fibrinogen band, (alpha beta gamma)2. Designation of the upper band as Fib420, an approximately 420-kDa homodimer of the formula (alpha E beta gamma)2, is based on the overwhelming proportion of alpha E subunits (> 80% of the total alpha chains) found in anti-VI-immunoprecipitable material from hepatoma cell medium. Several lines of evidence suggest that the alpha E subunit, alone or incorporated into fibrinogen, is more stable than the common alpha chain, a feature of potential clinical importance. Images PMID:8146165

  20. Prediction of high-grade cervical intraepithelial neoplasia in cytologically normal women by human papillomavirusesting

    PubMed Central

    Carozzi, F; Ronco, G; Confortini, M; Noferini, D; Maddau, C; Ciatto, S; Segnan, N

    2000-01-01

    Human papillomavirus (HPV) testing has been suggested for primary screening of cervical cancer. Prediction of future high-grade cervical lesions is crucial for effectiveness and cost. We performed a case control study in a retrospective cohort of women with at least two cervical smears, all but the last one being negative, from the organized cervical screening programme in Florence, Italy. We searched for high-risk HPV in all previous, archival, smears from cases (new histologically confirmed cervical intraepithelial neoplasia (CIN) grade II or worse) and in one previous smear from each control (last smear cytologically normal, matched by age and interval (latency) from last smear). We applied polymerase chain reaction (PCR), and the b-globin gene was used as a DNA preservation marker. High-risk HPV was identified in 71/92 (77.17%) previous smears from 79 cases and 17/332 controls (5.12%). The odds ratio (OR) was 63.76 (95% CI 30.57–132.96). Among cases the proportion of HPV-positive smears declined slightly with increasing latency. Among cases, HPV was found in 81.24% (95% CI 69.93–88.96%) of smears with latency < 4 years and in 67.80% (95% CI 47.72–82.93%) of those taken at longer intervals, up to 6 years. These findings suggest that testing for high-risk HPV allows predicting 80% of CINII/III 3 years before the cytological diagnosis and two thirds 6 years before. They also suggest that testing women negative for high-risk HPV at longer interval and strictly following-up women who are HPV positive could be an effective strategy for cervical cancer screening. © 2000 Cancer Research Campaign http://www.bjcancer.com PMID:11076654

  1. Erythropoietin triggers a burst of GATA-1 in normal human erythroid cells differentiating in tissue culture.

    PubMed Central

    Dalyot, N; Fibach, E; Ronchi, A; Rachmilewitz, E A; Ottolenghi, S; Oppenheim, A

    1993-01-01

    GATA-1 is a central transcription-activator of erythroid differentiation. In the present work we have studied the kinetics of its expression and activity during development of normal human erythroid progenitors, grown in primary cultures. In response to the addition of erythropoietin (Epo), the cells undergo proliferation and differentiation in a synchronized fashion. This recently developed experimental system allows biochemical dissection of erythroid differentiation in a physiological meaningful environment. No DNA-binding activity of GATA-1 could be detected before the addition of Epo, although a very low level of mRNA was observed. Following Epo addition there was a sharp parallel rise in both mRNA and DNA-binding activity, consistent with positive autoregulation of the GATA-1 gene. After reaching a peak on day 7-9, both mRNA and protein activity decreased. The binding activity of the ubiquitous factor SP1 showed a biphasic pattern; its second peak usually coincided with the GATA-1 peak, suggesting that SP1 also plays a specific role in erythroid maturation. The highest activity of GATA-1 per erythroid cell was found on day 6-8, immediately preceding the major rise in globin gene mRNA and in the number of hemoglobinized cells. The results imply that a high level of GATA-1 activity is necessary for globin gene expression and erythroid maturation, suggesting that a requirement for a threshold concentration of GATA-1 is part of the mechanism that determines the final steps of erythroid maturation. Images PMID:8371977

  2. LET and ion species dependence for cell killing in normal human skin fibroblasts.

    PubMed

    Tsuruoka, Chizuru; Suzuki, Masao; Kanai, Tatsuaki; Fujitaka, Kazunobu

    2005-05-01

    We studied the LET and ion species dependence of the RBE for cell killing to clarify the differences in the biological effects caused by the differences in the track structure that result from the different energy depositions for different ions. Normal human skin fibroblasts were irradiated with heavy-ion beams such as carbon, neon, silicon and iron ions that were generated by the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Science (NIRS) in Japan. Cell killing was measured as reproductive cell death using a colony formation assay. The RBE-LET curves were different for carbon ions and for the other ions. The curve for carbon ions increased steeply up to around 98 keV/microm. The RBE of carbon ions at 98 keV/microm was 4.07. In contrast, the curves for neon, silicon and iron ions had maximum peaks around 180 keV/microm, and the RBEs at the peak position ranged from 3.03 to 3.39. When the RBEs were plotted as a function of Z*2/beta2 (where Z* is the effective charge and beta is the relative velocity of the ion) instead of LET, the discrepancies between the RBE-LET curves for the different ion beams were reduced, but branching of the RBE-Z*2/beta2 curves still remained. When the inactivation cross section was plotted as a function of either LET or Z*2/beta2, it increased with increasing LET. However, the inactivation cross section was always smaller than the geometrical cross section. These results suggest that the differences in the energy deposition track structures of the different ion sources have an effect on cell killing.

  3. Signal transduction in normal and pathological thrombin-stimulated human platelets.

    PubMed

    Rendu, F; Marche, P; Viret, J; Maclouf, J; Lebret, M; Tenza, D; Caen, J; Levy-Toledano, S

    1987-04-01

    Human blood platelets stimulated by thrombin undergo very rapid morphological changes, the most characteristic of which are pseudopod formation and granule centralization. These early changes in shape are accompanied by a transient decrease (30%) in phosphatidyl inositol 4,5-bisphosphate (PIP2) which occurs in the first 10 s after thrombin addition. Transient decreases in phosphatidyl inositol 4-phosphate (PIP) and phosphatidyl inositol (PI) occur later (20-30 s). These events lead to the formation of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DG) and hence phosphatidate (PA). Two polypeptides are phosphorylated during the same time span: the myosin light chain (P20) and a 43 kDa protein (P43). Concomitant with these molecular changes, platelet 'release reaction' occurs, i.e., liberation of the different granule constituents into the external medium: the earliest concerns dense bodies which liberate adenine nucleotides, calcium and serotonin; alpha-granules then liberate adhesive and specific proteins and are followed by lysosomes which liberate hydrolases. Pathological platelets from patients with inherited disorders, presenting well-characterized and specific defects of either the platelet membrane (GT) or storage granules (GPS and HPS), have also been studied. The results obtained lead to the following conclusions: (1) the transducing system is normal in platelets unable to aggregate; (2) phosphorylation of P20 and P43 proteins can be complete with impaired release; and (3) when platelets lack alpha-granules the transducing system as well as the release of other granule populations are impaired. These results evidence the relationship between the absence of intraplatelet components and metabolic events.

  4. [Safety evaluation of tissue engineered medical devices using normal human mesenchymal stem cells].

    PubMed

    Sawada, Rumi; Ito, Tomomi; Tsuchiya, Toshie

    2007-05-01

    Several recent studies demonstrated the potential of bioengineering using somatic stem cells in regenerative medicine. Adult human mesenchymal stem cells (hMSCs) derived from bone marrow have the pluripotency to differentiate into cells of mesodermal origin, e.g., bone, cartilage, adipose, and muscle cells; they, therefore, have many potential clinical applications. On the other hand, stem cells possess a self-renewal capability similar to cancer cells. For safety evaluation of tissue engineered medical devices using normal hMSCs, in this study, we investigated the expression levels of several genes that affect cell proliferation in hMSCs during in vitro culture. We focused on the relationship between the hMSC proliferation and their transforming growth factor beta (TGFbeta) signaling during in vitro culture. The proliferation rate of hMSCs gradually decreased and cellular senescence was observed for about 3 months. The mRNA expressions of TGFbeta1, TGFbeta2, and TGFbeta receptor type I (TGFbetaRI) in hMSCs increased with the length of cell culture. The mRNA expressions of Smad3 increased, but those of c-myc and nucleostemin decreased with the length hMSCs were in in vitro culture. In addition, the expression profiles of the genes which regulate cellular proliferation in hMSCs were significantly different from those of cancer cells. In conclusion, hMSCs derived from bone marrow seldom underwent spontaneous transformation during 1-2 months in vitro culture for use in clinical applications. In hMSCs as well as in epithelial cells, growth might be controlled by the TGFbeta family signaling.

  5. The osmolyte strategy of normal human keratinocytes in maintaining cell homeostasis.

    PubMed

    Warskulat, Ulrich; Reinen, Andrea; Grether-Beck, Susanne; Krutmann, Jean; Häussinger, Dieter

    2004-09-01

    Compatible organic osmolytes, such as betaine, myoinositol, and taurine, are involved in cell volume homeostasis as well as in cell protection, for example, against oxidative stress. This so-called osmolyte strategy requires the expression of specific osmolyte transporting systems such as the betaine/gamma-amino-n-butyric acid (GABA) transporter, the sodium-dependent myoinositol transporter and the taurine transporter (TAUT). In contrast to liver, kidney, and neural cells, nothing is known about osmolytes in the skin. Here we report that primary normal human keratinocytes (NHK) express mRNA specific for the betaine/GABA transporter, for the sodium-dependent myoinositol transporter and for the TAUT. In comparison to normoosmotic (305 mosmol per L) controls, a 3-5-fold induction of mRNA expression for the betaine/GABA-, the sodium-dependent myoinositol- and the TAUT was observed within 6-24 h after hyperosmotic exposure (405 mosmol per L). Expression of osmolyte transporters was associated with an increased uptake of radiolabeled osmolytes. Conversely, hypoosmotic (205 mosmol per L) stimulation induced significant efflux of these osmolytes. Exposure to ultraviolet B (290-315 nm) or ultraviolet A (340-400 nm) radiation, which are major sources of oxidative stress in skin, significantly stimulated osmolyte uptake. Increased osmolyte uptake was associated with upregulation of mRNA steady-state levels for osmolyte transporters in irradiated cells. These studies demonstrate that NHK possess an osmolyte strategy, which is important for their capacity to maintain cell volume homeostasis and seems to be part of their response to UV radiation.

  6. Differential responses of normal human melanocytes to intra- and extracellular dsRNA.

    PubMed

    Wang, Suiquan; Liu, Dongyin; Jin, Rong; Zhu, Yiping; Xu, Aie

    2015-06-01

    Viral factor has been implicated in the etiopathogenesis of vitiligo. To elucidate the effects of viral double-stranded RNA (dsRNA) on melanocytes and to explore the underlying mechanisms, primary cultured normal human melanocytes were treated with synthetic viral dsRNA analog poly(I:C). The results demonstrated that poly(I:C)-triggered apoptosis when transfected into melanocytes, while extracellular poly(I:C) did not have that effect. Intracellular poly(I:C)-induced melanocyte death was decreased by RIG-I or MDA5 siRNA, but not by TLR3 siRNA. Both intracellular and extracellular poly(I:C) induced the expression of IFNB, TNF, IL6, and IL8. However, extracellular poly(I:C) demonstrated a much weaker induction capacity of cytokine genes than intracellular poly(I:C). Further analysis revealed that phosphorylation of TBK1, IRF3, IRF7, and TAK1 was differentially induced by intra- or extracellular poly(I:C). NFκB inhibitor Bay 11-7082 decreased the induction of all the cytokines by poly(I:C), suggesting the ubiquitous role of NFκB in the process. Poly(I:C) treatment also induced the phosphorylation of p38 and JNK in melanocytes. Both JNK and p38 inhibitors showed suppression on the cytokine induction by intra- or extracellular poly(I:C). However, only the JNK inhibitor decreased the intracellular poly(I:C)-induced melanocyte death. Taken together, this study provides the possible mechanism of viral factor in the pathogenesis of vitiligo.

  7. HOMER2, a Stereociliary Scaffolding Protein, Is Essential for Normal Hearing in Humans and Mice

    PubMed Central

    Azaiez, Hela; Shearer, A. Eliot; Huygen, Patrick L. M.; Bu, Fengxiao; Hildebrand, Michael S.; Ranum, Paul T.; Shibata, Seiji B.; Turner, Ann; Zhang, Yuzhou; Kimberling, William J.; Cornell, Robert A.; Smith, Richard J. H.

    2015-01-01

    Hereditary hearing loss is a clinically and genetically heterogeneous disorder. More than 80 genes have been implicated to date, and with the advent of targeted genomic enrichment and massively parallel sequencing (TGE+MPS) the rate of novel deafness-gene identification has accelerated. Here we report a family segregating post-lingual progressive autosomal dominant non-syndromic hearing loss (ADNSHL). After first excluding plausible variants in known deafness-causing genes using TGE+MPS, we completed whole exome sequencing in three hearing-impaired family members. Only a single variant, p.Arg185Pro in HOMER2, segregated with the hearing-loss phenotype in the extended family. This amino acid change alters a highly conserved residue in the coiled-coil domain of HOMER2 that is essential for protein multimerization and the HOMER2-CDC42 interaction. As a scaffolding protein, HOMER2 is involved in intracellular calcium homeostasis and cytoskeletal organization. Consistent with this function, we found robust expression in stereocilia of hair cells in the murine inner ear and observed that over-expression of mutant p.Pro185 HOMER2 mRNA causes anatomical changes of the inner ear and neuromasts in zebrafish embryos. Furthermore, mouse mutants homozygous for the targeted deletion of Homer2 present with early-onset rapidly progressive hearing loss. These data provide compelling evidence that HOMER2 is required for normal hearing and that its sequence alteration in humans leads to ADNSHL through a dominant-negative mode of action. PMID:25816005

  8. Ocular motor responses to abrupt interaural head translation in normal humans.

    PubMed

    Ramat, Stefano; Zee, David S

    2003-08-01

    We characterized the interaural translational vestibulo-ocular reflex (tVOR) in 6 normal humans to brief (approximately 200 ms), high-acceleration (0.4-1.4g) stimuli, while they fixed targets at 15 or 30 cm. The latency was 19 +/- 5 ms at 15-cm and 20 +/- 12 ms at 30-cm viewing. The gain was quantified using the ratio of actual to ideal behavior. The median position gain (at time of peak head velocity) was 0.38 and 0.37, and the median velocity gain, 0.52 and 0.62, at 15- and 30-cm viewing, respectively. These results suggest the tVOR scales proportionally at these viewing distances. Likewise, at both viewing distances, peak eye velocity scaled linearly with peak head velocity and gain was independent of peak head acceleration. A saccade commonly occurred in the compensatory direction, with a greater latency (165 vs. 145 ms) and lesser amplitude (1.8 vs. 3.2 deg) at 30- than 15-cm viewing. Even with saccades, the overall gain at the end of head movement was still considerably undercompensatory (medians 0.68 and 0.77 at 15- and 30-cm viewing). Monocular viewing was also assessed at 15-cm viewing. In 4 of 6 subjects, gains were the same as during binocular viewing and scaled closely with vergence angle. In sum the low tVOR gain and scaling of the response with viewing distance and head velocity extend previous results to higher acceleration stimuli. tVOR latency (approximately 20 ms) was lower than previously reported. Saccades are an integral part of the tVOR, and also scale with viewing distance.

  9. E-Cigarette Affects the Metabolome of Primary Normal Human Bronchial Epithelial Cells.

    PubMed

    Aug, Argo; Altraja, Siiri; Kilk, Kalle; Porosk, Rando; Soomets, Ursel; Altraja, Alan

    2015-01-01

    E-cigarettes are widely believed to be safer than conventional cigarettes and have been even suggested as aids for smoking cessation. However, while reasonable with some regards, this judgment is not yet supported by adequate biomedical research data. Since bronchial epithelial cells are the immediate target of inhaled toxicants, we hypothesized that exposure to e-cigarettes may affect the metabolome of human bronchial epithelial cells (HBEC) and that the changes are, at least in part, induced by oxidant-driven mechanisms. Therefore, we evaluated the effect of e-cigarette liquid (ECL) on the metabolome of HBEC and examined the potency of antioxidants to protect the cells. We assessed the changes of the intracellular metabolome upon treatment with ECL in comparison of the effect of cigarette smoke condensate (CSC) with mass spectrometry and principal component analysis on air-liquid interface model of normal HBEC. Thereafter, we evaluated the capability of the novel antioxidant tetrapeptide O-methyl-l-tyrosinyl-γ-l-glutamyl-l-cysteinylglycine (UPF1) to attenuate the effect of ECL. ECL caused a significant shift in the metabolome that gradually gained its maximum by the 5th hour and receded by the 7th hour. A second alteration followed at the 13th hour. Treatment with CSC caused a significant initial shift already by the 1st hour. ECL, but not CSC, significantly increased the concentrations of arginine, histidine, and xanthine. ECL, in parallel with CSC, increased the content of adenosine diphosphate and decreased that of three lipid species from the phosphatidylcholine family. UPF1 partially counteracted the ECL-induced deviations, UPF1's maximum effect occurred at the 5th hour. The data support our hypothesis that ECL profoundly alters the metabolome of HBEC in a manner, which is comparable and partially overlapping with the effect of CSC. Hence, our results do not support the concept of harmlessness of e-cigarettes.

  10. Ocular motor responses to abrupt interaural head translation in normal humans

    NASA Technical Reports Server (NTRS)

    Ramat, Stefano; Zee, David S.; Shelhamer, M. J. (Principal Investigator)

    2003-01-01

    We characterized the interaural translational vestibulo-ocular reflex (tVOR) in 6 normal humans to brief (approximately 200 ms), high-acceleration (0.4-1.4g) stimuli, while they fixed targets at 15 or 30 cm. The latency was 19 +/- 5 ms at 15-cm and 20 +/- 12 ms at 30-cm viewing. The gain was quantified using the ratio of actual to ideal behavior. The median position gain (at time of peak head velocity) was 0.38 and 0.37, and the median velocity gain, 0.52 and 0.62, at 15- and 30-cm viewing, respectively. These results suggest the tVOR scales proportionally at these viewing distances. Likewise, at both viewing distances, peak eye velocity scaled linearly with peak head velocity and gain was independent of peak head acceleration. A saccade commonly occurred in the compensatory direction, with a greater latency (165 vs. 145 ms) and lesser amplitude (1.8 vs. 3.2 deg) at 30- than 15-cm viewing. Even with saccades, the overall gain at the end of head movement was still considerably undercompensatory (medians 0.68 and 0.77 at 15- and 30-cm viewing). Monocular viewing was also assessed at 15-cm viewing. In 4 of 6 subjects, gains were the same as during binocular viewing and scaled closely with vergence angle. In sum the low tVOR gain and scaling of the response with viewing distance and head velocity extend previous results to higher acceleration stimuli. tVOR latency (approximately 20 ms) was lower than previously reported. Saccades are an integral part of the tVOR, and also scale with viewing distance.

  11. Normal human serum (HS) prevents oxidant-induced lysis of cultured endothelial cells (ECs)

    SciTech Connect

    Callahan, K.S.; Harlan, J.M.

    1986-03-01

    Most studies demonstrating oxidant lysis of cultured ECs are performed in serum-free media or media containing low concentrations of bovine serum. The authors found that HS protects human and bovine ECs from lysis caused by reagent H/sub 2/O/sub 2/ or glucose/glucose oxidase (GO)-generated H/sub 2/O/sub 2/. EC injury was assessed by /sup 51/Cr release, cell detachment, or trypan blue dye exclusion. Protective HS activity was dose-dependent with concentrations greater than or equal to 25% preventing lethal injury. Cytotoxicity at 24 hrs, induced by 20 mU/ml GO, was 90.1 +/- 5.2% without HS vs 1.7 +/- 4.6% with 25% HS present (20 exp). Similar protection was observed with heparinized plasma. Of note, comparable concentrations of bovine serum were devoid of protective activity. Addition of fatty acid-free albumin to the media was also without protective effect. Preliminary characterization showed HS activity was stable to 60/sup 0/C for 30 min, non-dialyzable at 25,000 MW cutoff, and retained in delipidated serum. The HS protection was not merely due to scavenging of exogenous H/sub 2/O/sub 2/ as A23187-induced EC lysis was also prevented by HS. Protective activity was not reproduced by purified cerruloplasmin or transferrin. In conclusion, unidentified factor(s) present in HS protect cultured ECs from oxidant-induced lysis. Since endothelium is normally exposed to 100% plasma, the authors suggest that in vitro studies of oxidant-mediated injury be performed in the presence of HS. Factor(s) in HS may play an important role in modulating oxidant-induced vascular injury in vivo.

  12. Radiation-quality dependent cellular response in mutation induction in normal human cells.

    PubMed

    Suzuki, Masao; Tsuruoka, Chizuru; Uchihori, Yukio; Kitamura, Hisashi; Liu, Cui Hua

    2009-09-01

    We studied cellular responses in normal human fibroblasts induced with low-dose (rate) or low-fluence irradiations of different radiation types, such as gamma rays, neutrons and high linear energy transfer (LET) heavy ions. The cells were pretreated with low-dose (rate) or low-fluence irradiations (approximately 1 mGy/7-8 h) of 137Cs gamma rays, 241Am-Be neutrons, helium, carbon and iron ions before irradiations with an X-ray challenging dose (1.5 Gy). Helium (LET = 2.3 keV/microm), carbon (LET = 13.3 keV/microm) and iron (LET = 200 keV/microm) ions were produced by the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan. No difference in cell-killing effect, measured by a colony forming assay, was observed among the pretreatment with different radiation types. In mutation induction, which was detected in the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus to measure 6-thioguanine resistant clones, there was no difference in mutation frequency induced by the X-ray challenging dose between unpretreated and gamma-ray pretreated cells. In the case of the pretreatment of heavy ions, X-ray-induced mutation was around 1.8 times higher in helium-ion pretreated and 4.0 times higher in carbon-ion pretreated cells than in unpretreated cells (X-ray challenging dose alone). However, the mutation frequency in cells pretreated with iron ions was the same level as either unpretreated or gamma-ray pretreated cells. In contrast, it was reduced at 0.15 times in cells pretreated with neutrons when compared to unpretreated cells. The results show that cellular responses caused by the influence of hprt mutation induced in cells pretreated with low-dose-rate or low-fluence irradiations of different radiation types were radiation-quality dependent manner.

  13. Beta-endorphin-induced inhibition and stimulation of insulin secretion in normal humans is glucose dependent.

    PubMed

    Giugliano, D; Cozzolino, D; Salvatore, T; Torella, R; D'Onofrio, F

    1988-09-01

    This study evaluated the effect of human beta-endorphin on pancreatic hormone levels and their responses to nutrient challenges in normal subjects. Infusion of 0.5 mg/h beta-endorphin caused a significant rise in plasma glucose concentrations preceded by a significant increase in peripheral glucagon levels. No changes occurred in the plasma concentrations of insulin and C-peptide. Acute insulin and C-peptide responses to intravenous pulses of different glucose amounts (0.33 g/kg and 5 g) and arginine (3 g) were significantly reduced by beta-endorphin infusion (P less than .01). This effect was associated with a significant reduction of the glucose disappearance rates, suggesting that the inhibition of insulin was of biological relevance. beta-Endorphin also inhibited glucose suppression of glucagon levels and augmented the glucagon response to arginine. To verify whether the modification of prestimulus glucose level could be important in these hormonal responses to beta-endorphin, basal plasma glucose concentrations were raised by a primed (0.5 g/kg) continuous (20 mg kg-1.min-1) glucose infusion. After stabilization of plasma glucose levels (350 +/- 34 mg/dl, t = 120 min), beta-endorphin infusion caused an immediate and marked increase in plasma insulin level (peak response 61 +/- 9 microU/ml, P less than .01), which remained elevated even after the discontinuation of opioid infusion. Moreover, the acute insulin response to a glucose pulse (0.33 g/kg i.v.) given during beta-endorphin infusion during hyperglycemia was significantly higher than the response obtained during euglycemia (171 +/- 32 vs. 41 +/- 7 microU/ml, P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

  14. The influence of aqueous extracts of selected Potentilla species on normal human colon cells.

    PubMed

    Tomczyk, Michał; Paduch, Roman; Wiater, Adrian; Pleszczyńska, Małgorzata; Kandefer-Szerszeń, Martyna; Szczodrak, Janusz

    2013-01-01

    Potentilla L. (Rosaceae) species have been used in traditional medicine in Asia, Europe and Northern America. This study analyzed the biological activity of aqueous extracts of Potentilla species (Rosaceae): Dasiphora fruticosa (syn. P. fruticosa), P. norvegica, P. pensylvanica, P. thuringiaca, P. crantzii and P. nepalensis. The activities were tested using MTT, NR and DPPH assays on normal human colon epithelium (CCD 841 CoTr) and colon myofibroblast (CCD-18Co) cells. Moreover, cell morphology using the May-Grünwald-Giemsa method, IL-6 by ELISA, and nitric oxide (NO) analysis with the Griess method in culture supernatants were performed after 24 h. Extracts were tested at dose levels between 25 and 250 microg/mL. For ELISA, 15 microg/mL was chosen. All extracts suppressed the metabolism of myofibroblasts, while epithelial cells' mitochondrial dehydrogenase activity decreased after incubation with extracts. All extracts showed a free radical scavenging (DPPH) effect in a concentration-dependent manner. The most potent was the extract from D. fruticosa, while the least action was observed for P. thuringiaca. Potentilla extracts stimulated, IL-6 production in tested cells but the level of the cytokine was found to decrease in epithelial cells. Pre-incubation of cells with LPS resulted in increased IL-6 secretion. Modulation of NO production after extract addition and cell pre-incubation with LPS was also observed. Potentilla extracts may be interesting natural factors modulating the main features of cells forming the colon wall, and thus may be potentially useful in the prophylaxis or healing of colon disorders.

  15. Characterization of cholecystokinin receptors (CCK-R) in normal and cancerous human pancreas

    SciTech Connect

    Singh, P.; Townsend, C.M. Jr.; Upp, J.; Laridjani, A.; Thompson, J.C.

    1986-03-01

    In this report is described, for the first time, the binding characteristics of CCK-R on normal (NOR) and cancerous (CAN) human pancreatic (P) membranes. NOR-P was collected from cadavers and CAN-P was collected at time of operation. CCK-R was measured from Scatchard plot of multi-point-binding-analysis, using I/sup 125/-BH-CCK-8-SO/sub 4/ (Amersham). The optimal binding conditions were similar for NOR and CAN-P. Maximum binding was observed at 30/sup 0/ after 45-60 min of incubation, in presence of 1.5 mM Ca/sup + +/. CCK-R in NOR-P ranged from 11.9 to 200.0 fmoles/mg protein, which probably reflects the degree of tissue deterioration before storage. Two classes of CCK-R were clearly definable with 10X difference in their binding affinities (K/sub d(1)/ = 0.04 nM and K/sub d(2)/ = 0.2-0.5 nM). Out of 5 PAN-C, 4 were +ve for CCK-R, with values ranging from 1.5-120 fmoles/mg protein, which probably reflects differences in hormone dependence or dedifferentiation, in situ, itself. In only one PAN-C, was there retention of both types of NOR-binding sites, with similar binding affinities. In other PAN-C the types and binding affinity of CCK-R underwent significant changes, indicating dedifferentiation or hormone independence of PAN-C, which may be either the cause or result of development of cancer.

  16. Surface markers on human lymphocytes: studies of normal subjects and of patients with primary immunodeficiencies

    PubMed Central

    Aiuti, F.; Lacava, V.; Garofalo, J. A.; D'Amelio, R.; D'Asero, C.

    1973-01-01

    Peripheral blood lymphocytes of twenty normal controls and twelve patients with primary immunodeficiencies were examined for surface membrane Ig and receptors for C3 complement (B cell markers) and for spontaneous rosette formation with sheep erythrocytes (T cell markers). In patients with defects in T cell function no lymphocytes forming spontaneous rosettes were seen. In patients with B cell deficiency they were normal or increased. Lymphocytes with membrane immunoglobulins were normal in patients with T cell defect and absent in patients with severe agammaglobulinaemia. Lymphocytes with receptors for C3 complement were increased in patients with T defect and normal in patients with most other forms of immunodeficiency studied. PMID:4587827

  17. Specificity of immunoglobulin M antibodies in normal human serum that participate in opsonophagocytosis and intracellular killing of Bacteroides fragilis and Bacteroides thetaiotaomicron by by human polymorphonuclear leukocytes.

    PubMed Central

    Bjornson, A B; Bjornson, H S; Kitko, B P

    1980-01-01

    Studies were performed to determine the specificity of immunoglobulin M (IgM) antibodies in normal human serum that participate in opsonophagocytosis and intracellular killing of Bacteroides fragilis 1365 and Bacteroides thetaiotaomicron 1343 by human polymorphonuclear leukocytes. Purified normal human IgM was adsorbed with washed heat-killed cells of the homologous strains and heterologous strains of B. fragilis, B. thetaiotaomicron, Bacteroides vulgatus, Bacteroides distasonis, and Bacteroides asaccharolyticus and with erythrocytes coated with outer membrane complex prepared from the homologous strains. Hypogammaglobulinemic serum was supplemented with the adsorbed IgM preparations, and the ability of the supplemented sera to support opsonophagocytosis and killing of B. fragilis 1365 and B. thetaiotaomicron 1343 by human polymorphonuclear leukocytes was measured in vitro under anaerobic conditions. Normal IgM adsorbed with heat-killed cells of B. fragilis 1365 and B. thetaiotaomicron 1343 or with erythrocytes coated with outer membrane complex prepared from these strains failed to restore the ability of hypogammaglobulinemic serum to support opsonophagocytosis and intracellular killing of the homologous strain. In contrast, adsorption of normal IgM with heat-killed cells of the heterologous strains did not alter its opsonophagocytosis-promoting activity for either test strain. These results indicated that the IgM antibodies in normal human serum that participate in opsonophagocytosis and intracellular killing of B. fragilis 1365 and B. thetaiotaomicron 1343 are directed against strain-specific antigenic determinants contained in the outer membrane complex. Images Fig. 5 Fig. 6 PMID:6160104

  18. Modulation of trigeminal reflex excitability in migraine: effects of attention and habituation on the blink reflex.

    PubMed

    de Tommaso, Marina; Murasecco, Donatella; Libro, Giuseppe; Guido, Marco; Sciruicchio, Vittorio; Specchio, Luigi Maria; Gallai, Virgilio; Puca, Francomichele

    2002-06-01

    The modulation of trigeminal reflex excitability in migraine patients was evaluated during the asymptomatic phase by studying the effects of attention, habituation and preconditioning stimulus on the R2 and R3 components of the blink reflex (BR). Fifty patients suffering from migraine without aura, 20 affected by migraine with aura and 35 sex- and age-matched controls were selected. In subgroups of migraine with-aura and without-aura patients, and normal controls, the blink reflex was elicited during different cognitive situations: (a) spontaneous mental activity; (b) stimulus anticipation; (c) recognition of target numbers. In the remaining subjects, R2 and R3 habituation was evaluated by repetitive stimulation at 1, 5, 10, 15, 20, 25 and 30 s intervals. The R2 and R3 recovery curves were also computed. A reduced R3 threshold with a normal pain threshold was found in migraine with-aura and without-aura patients; the R3 component was not significantly correlated with the pain thresholds in patients and controls. The R2 and R3 components were less influenced by the warning of the stimulus in migraine without-aura and migraine with-aura patients, in comparison with the control group. A slight increase of both R2 and R3 recovery after preconditioning stimulus was also observed in migraine patients, probably caused by a phenomenon of trigeminal hyperexcitability persisting after the last attack. The abnormal BR modulation by alerting expresses in migraine a dysfunction of adaptation capacity to environmental conditions, probably predisposing to migraine.

  19. Frequency analysis of multispectral photoacoustic images for differentiating malignant region from normal region in excised human prostate

    NASA Astrophysics Data System (ADS)

    Sinha, Saugata; Rao, Navalgund A.; Valluru, Keerthi S.; Chinni, Bhargava K.; Dogra, Vikram S.; Helguera, Maria

    2014-03-01

    Frequency domain analysis of the photoacoustic (PA) radio frequency signals can potentially be used as a tool for characterizing microstructure of absorbers in tissue. This study investigates the feasibility of analyzing the spectrum of multiwavelength PA signals generated by excised human prostate tissue samples to differentiate between malignant and normal prostate regions. Photoacoustic imaging at five different wavelengths, corresponding to peak absorption coefficients of deoxyhemoglobin, whole blood, oxyhemoglobin, water and lipid in the near infrared (NIR) (700 nm - 1000 nm) region, was performed on freshly excised prostate specimens taken from patients undergoing prostatectomy for biopsy confirmed prostate cancer. The PA images were co-registered with the histopathology images of the prostate specimens to determine the region of interest (ROI) corresponding to malignant and normal tissue. The calibrated power spectrum of each PA signal from a selected ROI was fit to a linear model to extract the corresponding slope, midband fit and intercept parameters. The mean value of each parameter corresponding to malignant and adjacent normal prostate ROI was calculated for each of the five wavelengths. The results obtained for 9 different human prostate specimens, show that the mean values of midband fit and intercept are significantly different between malignant and normal regions. In addition, the average midband fit and intercept values show a decreasing trend with increasing wavelength. These preliminary results suggest that frequency analysis of multispectral PA signals can be used to differentiate malignant region from the adjacent normal region in human prostate tissue.

  20. Influence of zinc deficiency on AKT-MDM2-P53 signaling axes in normal and malignant human prostate cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    With prostate being the highest zinc-accumulating tissue before the onset of cancer, the effects of physiologic levels of zinc on Akt-Mdm2-p53 and Akt-p21 signaling axes in human normal prostate epithelial cells (PrEC) and malignant prostate LNCaP cells were examined. Cells were cultured for 6 d in...

  1. Carbamazepine and folic acid in trigeminal neuralgia patients.

    PubMed Central

    al-Musaed, A A; Zakrzewska, J M; Bain, B J

    1992-01-01

    The effect of carbamazepine monotherapy on the red cell folate level of 133 patients with trigeminal neuralgia was evaluated. The patient group had a significantly lower mean value of red cell folate levels compared with 110 controls. No significant correlation was found between the red cell folate levels and the mean cell volume or haemoglobin values in either the carbamazepine or control group. In addition no significant correlation was found between the red cell folate levels and drug dosage. Administration of folic acid supplements raised the mean value of red cell folate significantly. Dietary folate intake was assessed in 43 trigeminal neuralgia patients and 33 matched control patients and there was no significant difference between the groups. Patients taking carbamazepine should be advised on a well-balanced diet rich in folate as opposed to being given a routine prescription of folic acid. PMID:1548649

  2. A Novel Pathophysiological Mechanism Contributing to Trigeminal Neuralgia

    PubMed Central

    Grasso, Giovanni; Landi, Alessandro; Alafaci, Concetta

    2016-01-01

    Trigeminal neuralgia (TN) is a form of neuropathic pain that affects the fifth cranial nerve, the most widely distributed nerve in the head. Although TN has been associated with a variety of pathological conditions, neurovascular compression on the trigeminal nerve as it exits the brainstem is the most frequent reported cause. This compression causes progressive demyelination of the nerve and subsequent aberrant neural transmission. Although several studies have clarified some pathophysiological mechanisms underlying TN, the molecular basis remains vague. Very recently the substitution of methionine 136 by valine (MET126Val) in sodium channel Nav1.6 in a case study of typical TN has suggested a new possible mechanism for TN. The findings of this new mutation provide novel information that warrants further conclusive investigation. PMID:27533070

  3. Trigeminal herpes zoster: early recognition and treatment are crucial

    PubMed Central

    Lovell, Ben

    2015-01-01

    Reactivation of varicella zoster virus (VZV) is not uncommon in older patients, particularly in cases of chronic autoimmune disorders and in patients taking immunosuppressant drugs. We present a case of a 57-year-old woman presenting with severe herpes zoster infection, involving the maxillary and ophthalmic branches of the trigeminal nerve. Despite an initial delay in instigating crucial antiviral treatment, the patient achieved an excellent recovery, with only some mild scarring at 2 months postinfection. Trigeminal herpes zoster is a potentially devastating clinical occurrence, and is associated with severe long-term neurological sequelae, including encephalitis, vision loss and postherpetic neuralgia. Physicians must be aware of risk factors and treatment modalities. PMID:25795749

  4. Cerebellopontine angle primitive neuroectodermal tumor mimicking trigeminal schwannoma

    PubMed Central

    Khan, Saad Akhtar; Ujjan, Badar Uddin; Salim, Adnan; Shamim, Shahzad

    2016-01-01

    Background: Primitive neuroectodermal tumors (PNETs) comprise a group of aggressive, poorly differentiated embryonal tumors occurring in central nervous system as well as in peripheral locations. Primary cerebellopontine angle (CPA) PNET is an extremely rare entity. It is important to have knowledge of this pathology and to be able to differentiate it from other commonly occurring CPA tumors, such as vestibular and trigeminal schwannomas. This distinction is essential because of the difference in the overall treatment plan and prognosis. Case Description: This report describes a case of a young male presenting with diplopia and numbness of face; magnetic resonance imaging showed a CPA mass. With a provisional diagnosis of trigeminal schwannoma, the patient underwent surgery. Histopathology provided a diagnosis of PNET. Conclusion: We discuss the importance of recognizing this rare condition and how this entity differs from the commonly occurring tumors. PMID:26862446

  5. Effect of beam channel plugging on the outcome of gamma knife radiosurgery for trigeminal neuralgia

    SciTech Connect

    Massager, Nicolas . E-mail: nmassage@ulb.ac.be; Nissim, Ouzi; Murata, Noriko; Devriendt, Daniel; Desmedt, Francoise; Vanderlinden, Bruno; Regis, Jean; Levivier, Marc

    2006-07-15

    Purpose: We studied the influence of using plugs for brainstem protection during gamma knife radiosurgery (GKR) of trigeminal neuralgia (TN), with special emphasis on irradiation doses delivered to the trigeminal nerve, pain outcomes, and incidence of trigeminal dysfunction. Methods and Materials: A GKR procedure for TN using an anterior cisternal target and a maximum dose of 90 Gy was performed in 109 patients. For 49 patients, customized beam channel blocking (plugs) were used to reduce the dose delivered to the brainstem. We measured the mean and integrated radiation doses delivered to the trigeminal nerve and the clinical course of patients treated with and without plugs. Results: We found that blocking increases the length of trigeminal nerve exposed to high-dose radiation, resulting in a significantly higher mean dose to the trigeminal nerve. Significantly more of the patients with blocking achieved excellent pain outcomes (84% vs. 62%), but with higher incidences of moderate and bothersome trigeminal nerve dysfunction (37% mild/10% bothersome with plugs vs. 30% mild/2% bothersome without). Conclusions: The use of plugs to protect the brainstem during GKR treatment for TN increases the dose of irradiation delivered to the intracisternal trigeminal nerve root and is associated with an important increase in the incidence of trigeminal nerve dysfunction. Therefore, beam channel blocking should be avoided for 90 Gy-GKR of TN.

  6. Trigeminal nerve morphology in Alligator mississippiensis and its significance for crocodyliform facial sensation and evolution.

    PubMed

    George, Ian D; Holliday, Casey M

    2013-04-01

    Modern crocodylians possess a derived sense of face touch, in which numerous trigeminal nerve-innervated dome pressure receptors speckle the face and mandible and sense mechanical stimuli. However, the morphological features of this system are not well known, and it remains unclear how the trigeminal system changes during ontogeny and how it scales with other cranial structures. Finally, when this system evolved within crocodyliforms remains a mystery. Thus, new morphological insights into the trigeminal system of extant crocodylians may offer new paleontological tools to investigate this evolutionary transformation. A cross-sectional study integrating histological, morphometric, and 3D imaging analyses was conducted to identify patterns in cranial nervous and bony structures of Alligator mississippiensis. Nine individuals from a broad size range were CT-scanned followed by histomorphometric sampling of mandibular and maxillary nerve divisions of the trigeminal nerve. Endocast volume, trigeminal fossa volume, and maxillomandibular foramen size were compared with axon counts from proximal and distal regions of the trigeminal nerves to identify scaling properties of the structures. The trigeminal fossa has a significant positive correlation with skull length and endocast volume. We also found that axon density is greater in smaller alligators and total axon count has a significant negative correlation with skull size. Six additional extant and fossil crocodyliforms were included in a supplementary scaling analysis, which found that size was not an accurate predictor of trigeminal anatomy. This suggests that phylogeny or somatosensory adaptations may be responsible for the variation in trigeminal ganglion and nerve size in crocodyliforms.

  7. Mitogen-stimulated phospholipid synthesis in normal and immune-deficient human B cells

    SciTech Connect

    Chien, M.M.; Yokoyama, W.M.; Ashman, R.F.

    1986-04-15

    Eight patients with common variable panhypogammaglobulinemia were shown in the in vitro Ig biosynthesis assay to have defective B cell responses to pokeweed mitogen (PWM). Phospholipid synthesis was assessed in the B cell plus monocyte fraction (MB) and irradiated T cells (T*) of patients and paired normal controls. Cell populations were studied separately and in the four possible combinations (1:1), with and without PWM, to reveal the effect of cell interactions. At 16 to 20 hr the mean stimulation index (SI) +/- standard error for MB cells alone was 1.01 +/- 0.02 for eight patients and 0.99 +/- 0.02 for the paired normals; the T* cell SI was 1.25 +/- 0.04 for patients and 1.28 +/- 0.05 for normals. Combinations of normal MB cells with normal T* cells showed significantly higher SI when compared with the combinations of normal MB cells with patient T* cells (p less than 0.005). However, the combination of patient MB cells with patient T* cells and the combination of patient MB cells with normal T* cells were not significantly different in SI (0.05 less than p less than 0.1). Isolation of patient and normal B cells, T* cells, and monocytes after the choline pulse showed that patient B cells gave a higher SI with normal T* help than with patient T* help. Of greatest interest is the finding that patient B cells that were defective in PWM-stimulated Ig production nevertheless showed a phospholipid synthesis response to PWM in the normal range, suggesting that the maturation defect in these B cells occurs later than the phospholipid synthesis acceleration step, or on a different pathway.

  8. Trigeminal autonomic cephalgia caused by recurrent posterior scleritis.

    PubMed

    Alim-Marvasti, Ali; Ho, Jason; Weatherall, Mark; Patel, Maneesh; George, Sheena; Viegas, Stuart

    2016-12-01

    A 40-year-old woman presented with a side-locked headache with autonomic features, which then switched sides before reverting to the original side. The atypical features of side swapping, partial response to indometacin and abnormal optic disc appearances ultimately led to a diagnosis of recurrent posterior scleritis. We discuss the differential diagnosis of trigeminal autonomic cephalgias and its secondary causes, and provide practical pointers for its investigation and management.

  9. Patterns and Variations in Microvascular Decompression for Trigeminal Neuralgia

    PubMed Central

    TODA, Hiroki; GOTO, Masanori; IWASAKI, Koichi

    2015-01-01

    Microvascular decompression (MVD) is a highly effective surgical treatment for trigeminal neuralgia (TN). Although there is little prospective clinical evidence, accumulated observational studies have demonstrated the benefits of MVD for refractory TN. In the current surgical practice of MVD for TN, there have been recognized patterns and variations in surgical anatomy and various decompression techniques. Here we provide a stepwise description of surgical procedures and relevant anatomical characteristics, as well as procedural options. PMID:25925756

  10. Quantifying glucose permeability and enhanced light penetration in ex vivo human normal and cancerous esophagus tissues with optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Zhao, Q. L.; Si, J. L.; Guo, Z. Y.; Wei, H. J.; Yang, H. Q.; Wu, G. Y.; Xie, S. S.; Li, X. Y.; Guo, X.; Zhong, H. Q.; Li, L. Q.

    2011-01-01

    We report our pilot results on quantification of glucose (G) diffusion permeability in human normal esophagus and ESCC tissues in vitro by using OCT technique. The permeability coefficient of 40% aqueous solution of G was found to be (1.74±0.04)×10-5 cm/s in normal esophagus and (2.45±0.06)×10-5 cm/s in ESCC tissues. The results from this study indicate that ESCC tissues had a higher permeability coefficient compared to normal esophageal tissues, and the light penetration depths gradually increase with the increase of applied topically with G time for the normal esophageal and ESCC tissues. The results indicate that the permeability coefficient of G in cancer tissues was 1.41-fold than that in normal tissues, and the light penetration depth for the ESCC tissues is significantly smaller than that of normal esophagus tissues in the same time range. These results demonstrate that the optical clearing of normal and cancer esophagus tissues are improved after application of G.

  11. Trigeminal neuralgia and chiropractic care: a case report

    PubMed Central

    Rodine, Robert J; Aker, Peter

    2010-01-01

    The following case describes a 68 year-old woman with a 7½ year history of worsening head and neck pain diagnosed as trigeminal neuralgia following surgical resection of a brain tumor. After years of unsuccessful management with medication and physical therapies, a therapeutic trial of chiropractic was carried out. Chiropractic care included ultrasound, manual therapies (manipulation and mobilization), soft tissue therapies, and home stretching exercises. After an initial treatment period followed by 18 months of supportive care the patient reported satisfactory improvement. It became evident that there were at least three sources of her symptoms: mechanical and/or degenerative neck pain, temporomandibular joint syndrome, and trigeminal neuralgia. While never completely pain-free, the patient continued to report that her pains reduced to minimal at times. At the most recent follow-up, the pain had not returned to pre-treatment intractable levels. This case study demonstrates the importance of diagnosing and treating multiple sources of pain and the positive role chiropractic care can have in the management of patients with these clinical conditions. The potential for convergence of sensory input from the upper three cervical segments and the trigeminal nerve via the trigeminocervical nucleus is discussed. PMID:20808617

  12. Human fibroblast strain with normal survival but abnormal postreplication repair after ultraviolet light irradiation

    SciTech Connect

    Doniger, J.; Barrett, S.F.; Robbins, J.H.

    1980-08-01

    Postreplication repair has been studied in ultraviolet light (UV-irradiated) fibroblast strains derived from eight apparently normal control donors and seven xeroderma pigmentosum patients. One control donor strain had an intermediate defect in postreplication repair similar to that in excision-deficient xeroderma pigmentosum fibroblasts. However, unlike the xeroderma pigmentosum strains, this control donor strain had normal UV-induced unscheduled DNA synthesis and normal survival after irradiation with UV. This unique fibroblast strain should be useful in studies designed to elucidate the possible role of postreplication repair in UV-induced carcinogenesis and mutagenesis.

  13. Cell bodies of the trigeminal proprioceptive neurons that transmit reflex contraction of the levator muscle are located in the mesencephalic trigeminal nucleus in rats.

    PubMed

    Fujita, Kenya; Matsuo, Kiyoshi; Yuzuriha, Shunsuke; Kawagishi, Kyutaro; Moriizumi, Tetsuji

    2012-12-01

    Since the levator and frontalis muscles lack interior muscle spindles despite being antigravity mixed muscles to involuntarily sustain eyelid opening and eyebrow lifting, this study has proposed a hypothetical mechanism to compensate for this anatomical defect. The voluntary contraction of fast-twitch fibres of the levator muscle stretches the mechanoreceptors in Müller's muscle to evoke proprioception, which continuously induces reflex contraction of slow-twitch fibres of the levator and frontalis muscles. This study confirmed the presence of cell bodies of the trigeminal proprioceptive neurons that transmit reflex contraction of the levator and frontalis muscles. After confirming that severing the trigeminal proprioceptive fibres that innervate the mechanoreceptors in Müller's muscle induced ipsilateral eyelid ptosis, Fluorogold was applied as a tracer to the proximal stump of the trigeminal proprioceptive nerve in rats. Fluorogold labelled the cell bodies of the trigeminal proprioceptive neurons, not in any regions of the rat brain including the trigeminal ganglion, but in the ipsilateral mesencephalic trigeminal nucleus neighbouring the locus ceruleus. Some Fluorogold particles accumulated in the area of the locus ceruleus. The trigeminal proprioceptive neurons could be considered centrally displaced ganglion cells to transmit afferent signal from the mechanoreceptors in Müller's muscle to the mesencephalon, where they may be able to make excitatory synaptic connections with both the oculomotor neurons and the frontalis muscle motoneurons for the involuntary coordination of the eyelid and eyebrow activities, and potentially to the locus ceruleus.

  14. A Computational Study of the Respiratory Airflow Characteristics in Normal and Obstructed Human Airways

    DTIC Science & Technology

    2014-01-01

    normal and three different obstructed airway geometries, consisting of symmetric, asym- metric, and random obstructions. Fig. 2 shows the geometric ...normal and obstructed airways Airway resistance is a measure of the opposition to the airflow caused by geometric properties, such as airway obstruction...pressure drops. Resistance values were dependent on the degree and geometric distribution of the obstruction sites. In the symmetric obstruction model

  15. Estimation of Human Foot Motion During Normal Walking Using Inertial and Magnetic Sensor Measurements

    DTIC Science & Technology

    2012-07-01

    OF: A foot motion filtering algorithm is presented for estimating foot kinematics relative to an earth -fixed reference frame during normal walking...Title ABSTRACT A foot motion filtering algorithm is presented for estimating foot kinematics relative to an earth -fixed reference frame during...filtering algorithm is presented for es- timating foot kinematics relative to an earth -fixed reference frame during normal walking motion. Algorithm

  16. Differential usage of the transport systems for folic acid and methotrexate in normal human T-lymphocytes and leukemic cells.

    PubMed

    Biswal, Bijesh Kumar; Verma, Rama Shanker

    2009-11-01

    Methotrexate (MTX) has been used as an effective anti-cancer drug for a long time. Conceptually, it is accepted that MTX and folic acid are transported by folate receptors (FRs) in cancerous cells, but the exact mechanism of MTX uptake in human leukemia is unknown. The objective of this study was to investigate different transport systems for FA and MTX, and to delineate their uptake mechanism in MOLT4, K562, Hut78 leukemia cells and normal human T cells. In MOLT4, uptake of MTX was higher than FA, similar to that of K562, Hut78 and normal T cells. In MOLT4 cells, MTX uptake was maximum at pH 7.4 whereas FA uptake was maximum at pH 4.5. Uptake of FA and MTX was significantly inhibited by anions, suggesting anion-dependent transport system. FA uptake was found to be energy dependent whereas MTX uptake was energy independent. RT-PCR and immunofluorescence results demonstrated the presence of reduced folate carrier as well as proton coupled folate transporter and absence of FR in MOLT4 and normal T cells. These data suggest the existence of two separate and independent carrier-mediated transport systems for the uptake of FA and MTX in normal and leukemic human T cells.

  17. Radiosensitivity of hepatoma cell lines and human normal liver cell lines exposed to 12C6+ ions

    NASA Astrophysics Data System (ADS)

    Jing, X.; Yang, J.; Li, W.; Guo, C.; Dang, B.; Wang, J.; Zhou, L.; Wei, W.; Gao, Q.

    AIM To investigate the radiosensitivity of hepatoma cell lines and human normal liver cell lines METHODS Accelerated carbon ions by heavy ion research facility in Lanzhou HIRFL have high LET We employed it to study the radiosensitivity of hepatoma cell lines SMMC-7721 and human normal liver cell lines L02 using premature chromosome condensation technique PCC Cell survive was documented by a colony assay Chromatid breaks were measured by counting the number of chromatid breaks and isochromatid breaks immediately after prematurely chromosome condensed by Calyculin-A RESULTS The survival curve of the two cell lines presented a good linear relationship and the survival fraction of L02 is higher than that of SMMC-7721 Additionally the two types of G 2 phase chromosome breaks chromatid breaks and isochromatid breaks of L02 are lower than that of SMMC-7721 CONCLUSION Human normal liver cell line have high radioresistance than that of hepatoma cell line It imply that it is less damage to normal organs when radiotherapy to hepatoma

  18. Expression of sodium channel SNS/PN3 and ankyrin(G) mRNAs in the trigeminal ganglion after inferior alveolar nerve injury in the rat.

    PubMed

    Bongenhielm, U; Nosrat, C A; Nosrat, I; Eriksson, J; Fjell, J; Fried, K

    2000-08-01

    The inferior alveolar nerve is a sensory branch of the trigeminal nerve that is frequently damaged, and such nerve injuries can give rise to persistent paraesthesia and dysaesthesia. The mechanisms behind neuropathic pain following nerve injury is poorly understood. However, remodeling of voltage-gated sodium channels in the neuronal membrane has been proposed as one possible mechanism behind injury-induced ectopic hyperexcitability. The TTX-resistant sodium channel SNS/PN3 has been implicated in the development of neuropathic pain after spinal nerve injury. We here study the effect of chronic axotomy of the inferior alveolar nerve on the expression of SNS/PN3 mRNA in trigeminal sensory neurons. The organization of sodium channels in the neuronal membrane is maintained by binding to ankyrin, which help link the sodium channel to the membrane skeleton. Ankyrin(G), which colocalizes with sodium channels in the initial segments and nodes of Ranvier, and is necessary for normal neuronal sodium channel function, could be essential in the reorganization of the axonal membrane after nerve injury. For this reason, we here study the expression of ankyrin(G) in the trigeminal ganglion and the localization of ankyrin(G) protein in the inferior alveolar nerve after injury. We show that SNS/PN3 mRNA is down-regulated in small-sized trigeminal ganglion neurons following inferior alveolar nerve injury but that, in contrast to the persistent loss of SNS/PN3 mRNA seen in dorsal root ganglion neurons following sciatic nerve injury, the levels of SNS/PN3 mRNA appear to normalize within a few weeks. We further show that the expression of ankyrin(G) mRNA also is downregulated after nerve lesion and that these changes persist for at least 13 weeks. This decrease in the ankyrin(G) mRNA expression could play a role in the reorganization of sodium channels within the damaged nerve. The changes in the levels of SNS/PN3 mRNA in the trigeminal ganglion, which follow the time course for

  19. In vivo reactivation of herpes simplex virus in rabbit trigeminal ganglia: electrode model.

    PubMed Central

    Green, M T; Rosborough, J P; Dunkel, E C

    1981-01-01

    The rabbit provides an excellent model for the study of ocular herpes because herpetic keratitis in the rabbit eye resembles human disease in its clinical features and in its propensity for spontaneous recurrence. This paper presents a method for the electrical induction of multiple episodes of in vivo reactivation of latent HSV-1 infection with peripheral shedding of virus. Physiological levels of current delivered via an electrode implanted over the trigeminal ganglion of latently infected animals has enabled us to modify and synchronize virus shedding in preocular tear film and to cause multiple episodes of reactivation in a single animal. For this reason, the model is well suited for antiviral efficacy testing and provides an excellent opportunity for investigation of virus-host cell interactions in latent and recurring herpetic disease. Images PMID:6271686

  20. Drug-Induced Hypersensitivity Syndrome Caused by Carbamazepine Used for the Treatment of Trigeminal Neuralgia

    PubMed Central

    Ono, Yuko; Shirafuji, Yoshinori; Hamada, Toshihisa; Masui, Masanori; Obata, Kyoichi; Yao, Mayumi; Kishimoto, Koji; Sasaki, Akira

    2016-01-01

    An 88-year-old man was diagnosed with trigeminal neuralgia, and treatment of carbamazepine 200 mg/day was initiated. About 6 weeks later, the patient developed a skin rash accompanied by fever. He was admitted to hospital and diagnosed with drug-induced hypersensitivity syndrome (DIHS) caused by carbamazepine. Oral carbamazepine treatment was stopped, but blood tests showed acute liver and acute renal failure. Drug-induced lymphocyte stimulation test (DLST) for carbamazepine, human herpes virus-6 (HHV-6) IgG, and CMV-HRP were negative. Oral prednisolone therapy was begun 18 days later. The titer of HHV-6 IgG antibodies was then detected (640 times). Following treatment, liver and renal function improved and the erythema disappeared. PMID:27885344

  1. Latent acyclovir-resistant herpes simplex virus type 1 in trigeminal ganglia of immunocompetent individuals.

    PubMed

    van Velzen, Monique; van Loenen, Freek B; Meesters, Roland J W; de Graaf, Miranda; Remeijer, Lies; Luider, Theo M; Osterhaus, Albert D M E; Verjans, Georges M G M

    2012-05-15

    Specific mutations within the hypervariable herpes simplex virus (HSV) gene thymidine kinase (TK) gene lead to acyclovir (ACV) resistance. To uncover the existence of latent ACV-resistant (ACV(R)) HSV-1, we determined the genetic and functional variability of the HSV-1 TK gene pool in paired trigeminal ganglia (TG) of 5 immunocompetent individuals. The latent virus pool consisted of a donor-specific HSV-1 quasispecies, including one major ACV-sensitive (ACV(S)) and multiple phylogenetic-related minor ACV(S) and ACV(R) TK variants. Contrary to minor variants, major TK variants were shared between paired TG. The data demonstrate the coexistence of phylogenetic-related ACV(S) and ACV(R) latent HSV-1 in human TG.

  2. Corticofugal projection patterns of whisker sensorimotor cortex to the sensory trigeminal nuclei.

    PubMed

    Smith, Jared B; Watson, Glenn D R; Alloway, Kevin D; Schwarz, Cornelius; Chakrabarti, Shubhodeep

    2015-01-01

    The primary (S1) and secondary (S2) somatosensory cortices project to several trigeminal sensory nuclei. One putative function of these corticofugal projections is the gating of sensory transmission through the trigeminal principal nucleus (Pr5), and some have proposed that S1 and S2 project differentially to the spinal trigeminal subnuclei, which have inhibitory circuits that could inhibit or disinhibit the output projections of Pr5. Very little, however, is known about the origin of sensorimotor corticofugal projections and their patterns of termination in the various trigeminal nuclei. We addressed this issue by injecting anterograde tracers in S1, S2 and primary motor (M1) cortices, and quantitatively characterizing the distribution of labeled terminals within the entire rostro-caudal chain of trigeminal sub-nuclei. We confirmed our anterograde tracing results by injecting retrograde tracers at various rostro-caudal levels within the trigeminal sensory nuclei to determine the position of retrogradely labeled cortical cells with respect to S1 barrel cortex. Our results demonstrate that S1 and S2 projections terminate in largely overlapping regions but show some significant differences. Whereas S1 projection terminals tend to cluster within the principal trigeminal (Pr5), caudal spinal trigeminal interpolaris (Sp5ic), and the dorsal spinal trigeminal caudalis (Sp5c), S2 projection terminals are distributed in a continuum across all trigeminal nuclei. Contrary to the view that sensory gating could be mediated by differential activation of inhibitory interconnections between the spinal trigeminal subnuclei, we observed that projections from S1 and S2 are largely overlapping in these subnuclei despite the differences noted earlier.

  3. Corticofugal projection patterns of whisker sensorimotor cortex to the sensory trigeminal nuclei

    PubMed Central

    Smith, Jared B.; Watson, Glenn D. R.; Alloway, Kevin D.; Schwarz, Cornelius; Chakrabarti, Shubhodeep

    2015-01-01

    The primary (S1) and secondary (S2) somatosensory cortices project to several trigeminal sensory nuclei. One putative function of these corticofugal projections is the gating of sensory transmission through the trigeminal principal nucleus (Pr5), and some have proposed that S1 and S2 project differentially to the spinal trigeminal subnuclei, which have inhibitory circuits that could inhibit or disinhibit the output projections of Pr5. Very little, however, is known about the origin of sensorimotor corticofugal projections and their patterns of termination in the various trigeminal nuclei. We addressed this issue by injecting anterograde tracers in S1, S2 and primary motor (M1) cortices, and quantitatively characterizing the distribution of labeled terminals within the entire rostro-caudal chain of trigeminal sub-nuclei. We confirmed our anterograde tracing results by injecting retrograde tracers at various rostro-caudal levels within the trigeminal sensory nuclei to determine the position of retrogradely labeled cortical cells with respect to S1 barrel cortex. Our results demonstrate that S1 and S2 projections terminate in largely overlapping regions but show some significant differences. Whereas S1 projection terminals tend to cluster within the principal trigeminal (Pr5), caudal spinal trigeminal interpolaris (Sp5ic), and the dorsal spinal trigeminal caudalis (Sp5c), S2 projection terminals are distributed in a continuum across all trigeminal nuclei. Contrary to the view that sensory gating could be mediated by differential activation of inhibitory interconnections between the spinal trigeminal subnuclei, we observed that projections from S1 and S2 are largely overlapping in these subnuclei despite the differences noted earlier. PMID:26483640

  4. Shogaols from Zingiber officinale protect IMR32 human neuroblastoma and normal human umbilical vein endothelial cells from beta-amyloid(25-35) insult.

    PubMed

    Kim, Darrick S H L; Kim, Dong-Seon; Oppel, Marissa N

    2002-04-01

    From the rhizome of Zingiber officinale L. (Zingiberaceae), four shogaols that protect IMR32 human neuroblastoma and normal human umbilical vein endothelial cells from beta-amyloid(25 - 35) insult at EC50 = 4.5 - 81 microM were isolated. The efficacy of cell protection from beta-amyloid(25 - 35) insult by these shogaols was shown to improve as the length of the side chain increases.

  5. Ion channel expression and function in normal and osteoarthritic human synovial fluid progenitor cells.

    PubMed

    Bertram, Karri L; Banderali, Umberto; Tailor, Pankaj; Krawetz, Roman J

    2016-01-01

    Osteoarthritis (OA) is a chronic disease affecting the cartilage of over 15% of Canadians. Synovial fluid mesenchymal progenitor cells (sfMPCs) are present in joints and are thought to contribute to healing. OA sfMPCs have a greater proliferative ability but decreased chondrogenic potential. However, little is known about the factors influencing/regulating the differences between normal and OA sfMPCs. Recently, our lab has shown that sfMPC chondrogenic differentiation in vitro is favorably biased toward a similar osmotic environment as they experience in vivo. The current study now examines the expression and functionality of a variety of ion channels in sfMPCs derived from normal individuals and early OA patients. Results indicated that there is differential ion channel regulation at the functional level and expression level in early OA sfMPCs. All ion channels were upregulated in early OA compared to normal sfMPCs with the exception of KCNMA1 at the mRNA level. At the protein level, TRPV4 was over expressed in early OA sfMPCs, while KCNJ12 and KCNMA1 were unchanged between normal and early OA sfMPCs. At the functional level, the inward rectifying potassium channel was under expressed in early OA sfMPCs, however the membrane potential was unchanged between normal and early OA sfMPCs. In the synovial environment itself, a number of differences in ion concentration between normal and early OA synovial fluid were observed. These findings suggest that normal and OA progenitor cells demonstrate functional differences in how they interact with the synovial ion environment.

  6. Classical dynamin DNM1 and DNM3 genes attain maximum expression in the normal human central nervous system.

    PubMed

    Romeu, Antoni; Arola, Lluís

    2014-03-28

    Dynamin is a super-family of large GTPase proteins that polymerise during their biological activity. Dynamin polymers form around lipid tubes and contribute to the membrane fission and scission of nascent vesicles from parent membranes. Here we used the NCBI Gene Expression Omnibus (GEO) database and the BioGPS gene expression portal to study differential dynamin gene expression in normal human organs or tissues. From the GDS1096 and GDS596 dataset, we downloaded the relative expression levels of dynamin-related genes (presented as percentages), with respect to all of the other genes on the array (platform Affymetrix GPL96), which includes the best characterised human genes. The expression profiles of dynamin in the central nervous system (CNS) are clearly distinct from the expression profiles in the other organs or tissues studied. We found that the classical dynamin DNM1 and DNM3 genes reach their maximum expression levels (100% of maximal expression) in all normal human CNS tissues studied. This is in contrast to the expression profile in the other normal human organs or tissues studied, in which both dynamin DNM1 and DNM3 genes showed approximately 50% maximal expression. This data mining analysis supports the concept that there is a relationship between the synapse and the molecular function of dynamin, suggesting a new field of work in the study of neurodegenerative diseases.

  7. Comparison of normalization methods for Illumina BeadChip HumanHT-12 v3

    PubMed Central

    2010-01-01

    Background Normalization of microarrays is a standard practice to account for and minimize effects which are not due to the controlled factors in an experiment. There is an overwhelming number of different methods that can be applied, none of which is ideally suited for all experimental designs. Thus, it is important to identify a normalization method appropriate for the experimental setup under consideration that is neither too negligent nor too stringent. Major aim is to derive optimal results from the underlying experiment. Comparisons of different normalization methods have already been conducted, none of which, to our knowledge, comparing more than a handful of methods. Results In the present study, 25 different ways of pre-processing Illumina Sentrix BeadChip array data are compared. Among others, methods provided by the BeadStudio software are taken into account. Looking at different statistical measures, we point out the ideal versus the actual observations. Additionally, we compare qRT-PCR measurements of transcripts from different ranges of expression intensities to the respective normalized values of the microarray data. Taking together all different kinds of measures, the ideal method for our dataset is identified. Conclusions Pre-processing of microarray gene expression experiments has been shown to influence further downstream analysis to a great extent and thus has to be carefully chosen based on the design of the experiment. This study provides a recommendation for deciding which normalization method is best suited for a particular experimental setup. PMID:20525181

  8. Tissue specific DNA methylation in normal human breast epithelium and in breast cancer.

    PubMed

    Avraham, Ayelet; Cho, Sean Soonweng; Uhlmann, Ronit; Polak, Mia Leonov; Sandbank, Judith; Karni, Tami; Pappo, Itzhak; Halperin, Ruvit; Vaknin, Zvi; Sella, Avishay; Sukumar, Saraswati; Evron, Ella

    2014-01-01

    Cancer is a heterogeneous and tissue-specific disease. Thus, the tissue of origin reflects on the natural history of the disease and dictates the therapeutic approach. It is suggested that tissue differentiation, mediated mostly by epigenetic modifications, could guide tissue-specific susceptibility and protective mechanisms against cancer. Here we studied breast specific methylation in purified normal epithelium and its reflection in breast cancers. We established genome wide methylation profiles of various normal epithelial tissues and identified 110 genes that were differentially methylated in normal breast epithelium. A number of these genes also showed methylation alterations in breast cancers. We elaborated on one of them, TRIM29 (ATDC), and showed that its promoter was hypo-methylated in normal breast epithelium and heavily methylated in other normal epithelial tissues. Moreover, in breast carcinomas methylation increased and expression decreased whereas the reverse was noted for multiple other carcinomas. Interestingly, TRIM29 regulation in breast tumors clustered according to the PAM50 classification. Thus, it was repressed in the estrogen receptor positive tumors, particularly in the more proliferative luminal B subtype. This goes in line with previous reports indicating tumor suppressive activity of TRIM29 in estrogen receptor positive luminal breast cells in contrast to oncogenic function in pancreatic and lung cancers. Overall, these findings emphasize the linkage between breast specific epigenetic regulation and tissue specificity of cancer.

  9. The blink reflex and the corneal reflex are followed by cortical activity resembling the nociceptive potentials induced by trigeminal laser stimulation in man.

    PubMed

    de Tommaso, M; Libro, G; Guido, M; Sciruicchio, V; Puca, F

    2001-09-07

    Laser stimulation of the supraorbital regions evokes brain potentials (LEPs) related to trigeminal nociception. The aim of this study was to record the R2 component of the blink reflex and the corneal reflex in 20 normal subjects, comparing the scalp activity following these reflexes with the nociceptive potentials evoked by CO2 laser stimulation of supraorbital regions. Cortical and muscular reflexes evoked by stimulation of the first trigeminal branch were recorded simultaneously. The R2 component of the blink reflex and the corneal reflex were followed by two cortical peaks, which resembled morphologically N-P waves of LEPs. The two peaks demonstrated a difference in latency of approximately 40 ms, which is consistent with activation time of nociception. This finding suggests that these reflexes are induced by activation of small pain-related fibers.

  10. Pleiotropic roles of Notch signaling in normal, malignant, and developmental hematopoiesis in the human

    PubMed Central

    Kushwah, Rahul; Guezguez, Borhane; Lee, Jung Bok; Hopkins, Claudia I; Bhatia, Mickie

    2014-01-01

    The Notch signaling pathway is evolutionarily conserved across species and plays an important role in regulating cell differentiation, proliferation, and survival. It has been implicated in several different hematopoietic processes including early hematopoietic development as well as adult hematological malignancies in humans. This review focuses on recent developments in understanding the role of Notch signaling in the human hematopoietic system with an emphasis on hematopoietic initiation from human pluripotent stem cells and regulation within the bone marrow. Based on recent insights, we summarize potential strategies for treatment of human hematological malignancies toward the concept of targeting Notch signaling for fate regulation. PMID:25252682

  11. Human uracil DNA N-glycosidase: studies in normal and repair defective cultured fibroblasts.

    PubMed Central

    Kuhnlein, U; Lee, B; Linn, S

    1978-01-01

    Uracil DNA N-glycosidase, an enzyme which participates in the excision of uracil from DNA, was measured in extracts from fibroblasts lines cultured from normal subjects, from several subjects with the genetic disease xeroderma pigmentosum, and from a subject with ataxia telangiectasia. The cell lines representative of complementation groups A and D of xeroderma pigmentosum and of ataxia telangiectasia had roughly the same level of activity as did the normal cells. On the other hand, cells from two xeroderma pigmentosum variants (XP4BE and XP13BE) had roughly half the normal level of activity, and cells from the heterozygous mother of XP4BE had an intermediate level of activity. In spite of these quantitative differences, no systematic alterations in reaction characteristics, apparent Km for substrate, or purification characteristics were noted for enzyme from any of the lines. Thus a causal relationship, if any, between levels of activity and the disease symptoms is equivocal. PMID:643602

  12. Effects of corticosteroids on the proliferation of normal and abnormal human connective tissue cells.

    PubMed

    Priestley, G C; Brown, J C

    1980-01-01

    Four corticosteroids were tested in vitro for effect on the proliferation of four strains of fibroblasts from scleroderma skin, four strains from normal adult skin and four strains of rheumatoid synovial cells. Significant effects on fibroblasts occurred only at the highest steroid concentration tested (10 microgram/ml) where the inhibitory ranking of the steriods was clobetasol propionate greater than clobetasone butyrate greater than betamethasone valerate greater than hydrocortisone. Hydrocortisone and betamethasone valerate stimulated proliferation of two normal strains, had no certain effect on the scleroderma group, and inhibited growth of synovial cells. Clobetasone butyrate and clobetasol propionate inhibited growth of all cells. All four steroids substantially reduced acid mucopolysaccharide secretion by scleroderma fibroblasts. These results suggest that fibroblasts from normal and abnormal skin show only small differences in their responses to corticosteroids in vitro, but contrast sharply with the mouse L-929 fibroblasts previously used in some assays of topical corticosteroid potency.

  13. The molecular and cellular response of normal and progressed human bronchial epithelial cells to HZE particles

    NASA Astrophysics Data System (ADS)

    Story, Michael; Ding, Liang-Hao; Minna, John; Park, Seong-mi; Larsen, Jill

    We have used a model of non-oncogenically immortalized normal human bronchial epithelial cells to determine the response of such cells to particles found outside the protection of the earth’s electromagnetic field. We have identified an enhanced frequency of cellular transformation, as measured by growth in soft agar, for both 56Fe and 28Si (1 GeV/n) that is maximal (4-6 fold) at 0.25 Gy and 0.40 Gy, respectively. At 4 months post-irradiation 38 individual soft agar clones were isolated. These clones were characterized extensively for cellular and molecular changes. Gene expression analysis suggested that these clones had down-regulated several genes associated with anti-oxidant pathways including GLS2, GPX1 and 4, SOD2, PIG3, and NQO1 amongst others. As a result, many of these transformed clones were exposed to high levels of intracellular radical oxygen species (ROS), although there appeared not to be any enhanced mitochondrial ROS. DNA repair pathways associated with ATM/ATR signaling were also upregulated. However, these transformants do not develop into tumors when injected into immune-compromised mice, suggesting that they have not progressed sufficiently to become oncogenic. Therefore we chose 6 soft agar clones for continuous culture for an additional 14 months. Amongst the 6 clones, only one clone showed any significant change in phenotype. Clone 3kt-ff.2a, propagated for 18 months, were 2-fold more radioresistant, had a shortened doubling time and the background rate of transformation more than doubled. Furthermore, the morphology of transformed clones changed. Clones from this culture are being compared to the original clone as well as the parental HBEC3KT and will be injected into immune-compromised mice for oncogenic potential. Oncogenically progressed HBECs, HBEC3KT cells that overexpress a mutant RAS gene and where p53 has been knocked down, designated HBEC3KTR53, responded quite differently to HZE particle exposure. First, these cells are more

  14. Dyshormonogenetic goiter: presence of an inhibitor of normal human thyroid peroxidase.

    PubMed

    Rosenthal, D; Carvalho-Guimarães, D P; Knobel, M; Medeiros-Neto, G A

    1990-12-01

    A dialyzable, thermostable inhibitor of normal thyroid peroxidase (TPO), with UV absorption maximum at 250-260 nm, was found in the digitonized, washed particulate fraction of two dyshormonogenetic goiters. No intrinsic TPO iodide-oxidation activity was detectable in either of these goiters, and their TPO iodination activity was below the method sensitivity threshold, even after dialysis. These findings could be explained by an absent or abnormal TPO associated with the synthesis of a TPO-inhibitor, or by the irreversible inhibition of a normal enzyme by the inhibitor.

  15. Conductivity of normal and pathological human erythrocytes (homozygous beta-thalassemia) at radiowave frequencies.

    PubMed

    Ballario, C; Bonincontro, A; Cametti, C; Rosi, A; Sportelli, L

    1984-01-01

    The conductivity of normal and homozygous beta-thalassemic erythrocyte suspensions has been measured over the frequency range from 5 KHz to 100 MHz in the temperature interval from 5 to 45 degrees C. The electrical parameters of the membrane, i.e., the capacitance CM and the conductance GM per unit surface have been calculated from an expression given by Hanai for the conductivity of a suspension of ellipsoidal particles covered with a shell. Some interesting differences between the normal and pathological state are evidentiated.

  16. Protein differences between normal and oligospermic human sperm demonstrated by two-dimensional gel electrophoresis.

    PubMed

    Morgentaler, A; Schopperle, W M; Crocker, R H; DeWolf, W C

    1990-11-01

    Protein expression by sperm obtained from men with normal semen analysis and men with oligospermia were evaluated by two-dimensional gel electrophoresis. Proteins were solubilized in a 9.5 M urea/2% Nonidet-P40 (LKB, Bromma, Sweden) lysis buffer and underwent second dimension separation on 10 to 16% polyacrylamide gradient gels. A set of 36 invariant proteins was identified in all normospermic samples, whereas 8 of 10 evaluable oligospermic samples lacked 1 or more of the invariant proteins. Proteins absent in oligospermic samples may be critical to normal sperm function and may serve as markers for infertility.

  17. Frequency-domain photon migration measurements of normal and malignant tissue optical properties in a human subject

    SciTech Connect

    Fishkin, J.B.; Coquoz, O.; Anderson, E.R.; Brenner, M.; Tromberg, B.J. |

    1997-01-01

    A 1-GHz multifrequency, multiwavelength frequency-domain photon migration instrument is used to measure quantitatively the optical absorption ({mu}{sub a}) and effective optical scattering ({mu}{sub s}{sup {prime}}) of normal and malignant tissues in a human subject. Large ellipsoidal ({approximately}10-cm major axis, {approximately}6-cm minor axes) subcutaneous malignant lesions were compared with adjacent normal sites in the abdomen and back. Absorption coefficients recorded at 674, 811, 849, and 956 nm were used to calculate tissue hemoglobin concentration (oxyhemoglobin, deoxyhemoglobin, and total), water concentration, hemoglobin oxygen saturation, and blood volume fraction {ital in vivo}. Our results show that the normal and the malignant tissues measured in the patient have clearly resolvable optical and physiological property differences that may be broadly useful in identifying and characterizing tumors.{copyright} 1997 Optical Society of America

  18. Polarization sensitive changes in the human macula associated with normal aging and age-related macular degeneration

    NASA Astrophysics Data System (ADS)

    VanNasdale, Dean Allan, Jr.

    2011-12-01

    The human macula occupies a relatively small, but crucial retinal area, as it is the location responsible for our most acute spatial vision and best color discrimination. Localizing important landmarks in the retina is difficult even in normal eyes where morphological inter-individual variability is high. This becomes even more challenging in the presence of sight-threatening pathology. With respect to the human macula, there remains a significant gap in the understanding of normal structure and function. Even less is known about the pathological mechanisms that occur in sight-threatening diseases including age-related macular degeneration. Because relatively little is known about normal aging changes, it is also difficult to differentiate those changes from changes associated with retinal disease. To better understand normal and pathological changes in the macula, imaging techniques using specific optical signatures are required. Structural features in the macula can be distinguished based on their intrinsic properties using specific light/tissue interactions. Because of the high degree of structural regularity in the macula, polarization sensitive imaging is potentially a useful tool for evaluating the morphology and integrity of the cellular architecture for both normal individuals and those affected by disease. In our investigations, we used polarization sensitive imaging to determining normal landmarks that are important clinically and for research investigations. We found that precision and accuracy in localizing the central macula was greatly improved through the use of polarization sensitive imaging. We also found that specific polarization alterations can be used to demonstrate systematic changes as a function of age, disproportionately affecting the central macular region. When evaluating patients with age-related macular degeneration, we found that precision and accuracy of localizing the central macula was also improved, even when significant pathology

  19. GENE EXPRESSION PROFILING OF NORMAL HUMAN BRONCHIAL EPITHELIAL CELLS EXPOSED TO TRIVALENT ARSENICALS AND DIMETHYLTHIOARSINIC ACID

    EPA Science Inventory

    Lung is a major target for arsenic carcinogenesis in humans. However, the carcinogenic mode of action of arsenicals is unknown. We investigated, in human bronchial epithelial (BEAS2B) cells, the effects of inorganic arsenic (iAsIII), monomethylarsonous acid (MMAIII), dimethylarsi...

  20. NIH Human Microbiome Project defines normal bacterial makeup of the body

    Cancer.gov

    Microbes inhabit just about every part of the human body, living on the skin, in the gut, and up the nose. Sometimes they cause sickness, but most of the time, microorganisms live in harmony with their human hosts, providing vital functions essential for

  1. MEETING AT SAN DIEGO, CA: GENE EXPRESSION IN NORMAL HUMAN KERATINOCYTES MODULATED BY TRIVALENT ARSENICALS

    EPA Science Inventory

    Arsenic exposure has been correlated with the development of several human cancers including those found in the skin, lung, liver, kidney and urinary bladder. Humans are generally exposed to inorganic forms of arsenic, which may be inhaled or ingested. Arsenic forms mono- and di-...

  2. MEETING AT CAMBRIDGE, MA: GENE EXPRESSION IN NORMAL HUMAN KERATINOCYTES MODULATED BY TRIVALENT ARSENICALS

    EPA Science Inventory

    Arsenic exposure has been correlated with the development of several human cancers including those found in the skin, lung, liver, kidney and urinary bladder. Humans are generally exposed to inorganic forms of arsenic, which may be inhaled or ingested. Arsenic forms mono- and d...

  3. Transcriptome-scale similarities between mouse and human skeletal muscles with normal and myopathic phenotypes

    PubMed Central

    Kho, Alvin T; Kang, Peter B; Kohane, Isaac S; Kunkel, Louis M

    2006-01-01

    Background Mouse and human skeletal muscle transcriptome profiles vary by muscle type, raising the question of which mouse muscle groups have the greatest molecular similarities to human skeletal muscle. Methods Orthologous (whole, sub-) transcriptome profiles were compared among four mouse-human transcriptome datasets: (M) six muscle groups obtained from three mouse strains (wildtype, mdx, mdx5cv); (H1) biopsied human quadriceps from controls and Duchenne muscular dystrophy patients; (H2) four different control human muscle types obtained at autopsy; and (H3) 12 different control human tissues (ten non-muscle). Results Of the six mouse muscles examined, mouse soleus bore the greatest molecular similarities to human skeletal muscles, independent of the latters' anatomic location/muscle type, disease state, age and sampling method (autopsy versus biopsy). Significant similarity to any one mouse muscle group was not observed for non-muscle human tissues (dataset H3), indicating this finding to be muscle specific. Conclusion This observation may be partly explained by the higher type I fiber content of soleus relative to the other mouse muscles sampled. PMID:16522209

  4. Case Report: Trigeminal Neuralgia Caused by a Minute Meningioma with Hyperostosed Suprameatal Tubercle.

    PubMed

    Ishi, Yukitomo; Asaoka, Katsuyuki; Sugiyama, Taku; Yokoyama, Yuka; Yamazaki, Kazuyoshi; Echizenya, Sumire; Itamoto, Koji; Echizenya, Kohei

    2015-01-01

    Cerebellopontine angle tumors might occasionally provoke trigeminal neuralgia but are usually large enough to be diagnosed radiographically. We present a case of trigeminal neuralgia caused by a very small meningioma covering the suprameatal tubercle that displayed hyperostosis at the entrance of Meckel's cave and was not obvious on routine magnetic resonance (MR) images. A 72-year-old woman with intractable trigeminal neuralgia in the left V3 territory was referred to our institution. Preoperative imaging studies revealed that the left trigeminal nerve was medially distorted at the entrance of Meckel's cave by a laterally seated bone bulge covered by a minute enhanced lesion. Trigeminal nerve decompression surgery was performed via a retrosigmoid intradural suprameatal approach. We found a small meningioma that had compressed and flattened the trigeminal nerve root at the entrance of Meckel's cave, which was grossly and totally removed by suprameatal tubercle resection. There was no vascular compression of the trigeminal nerve root. The trigeminal neuralgia ceased completely after the operation. Accurate preoperative determination of the causative pathologies is essential to achieve adequate surgical results after microvascular decompression for neurovascular compression syndrome. Because conventional MR sequences are inadequate for the precise interpretation of complex neurovascular anatomy in the cerebellopontine angle and such small tumors can be overlooked on routine MR studies, high-resolution thin-slice MR examinations and careful radiological interpretations are required for correct diagnosis and treatment.

  5. Case Report: Trigeminal Neuralgia Caused by a Minute Meningioma with Hyperostosed Suprameatal Tubercle

    PubMed Central

    Ishi, Yukitomo; Asaoka, Katsuyuki; Sugiyama, Taku; Yokoyama, Yuka; Yamazaki, Kazuyoshi; Echizenya, Sumire; Itamoto, Koji; Echizenya, Kohei

    2015-01-01

    Cerebellopontine angle tumors might occasionally provoke trigeminal neuralgia but are usually large enough to be diagnosed radiographically. We present a case of trigeminal neuralgia caused by a very small meningioma covering the suprameatal tubercle that displayed hyperostosis at the entrance of Meckel's cave and was not obvious on routine magnetic resonance (MR) images. A 72-year-old woman with intractable trigeminal neuralgia in the left V3 territory was referred to our institution. Preoperative imaging studies revealed that the left trigeminal nerve was medially distorted at the entrance of Meckel's cave by a laterally seated bone bulge covered by a minute enhanced lesion. Trigeminal nerve decompression surgery was performed via a retrosigmoid intradural suprameatal approach. We found a small meningioma that had compressed and flattened the trigeminal nerve root at the entrance of Meckel's cave, which was grossly and totally removed by suprameatal tubercle resection. There was no vascular compression of the trigeminal nerve root. The trigeminal neuralgia ceased completely after the operation. Accurate preoperative determination of the causative pathologies is essential to achieve adequate surgical results after microvascular decompression for neurovascular compression syndrome. Because conventional MR sequences are inadequate for the precise interpretation of complex neurovascular anatomy in the cerebellopontine angle and such small tumors can be overlooked on routine MR studies, high-resolution thin-slice MR examinations and careful radiological interpretations are required for correct diagnosis and treatment. PMID:26351448

  6. Temporal variations in sirtuin expression under normal and ultraviolet B-induced conditions and their correlation to energy levels in normal human epidermal keratinocytes.

    PubMed

    Pelle, Edward; Dong, Kelly; Pernodet, Nadine

    2015-01-01

    Sirtuins are post-translational modifiers that affect transcriptional signaling, metabolism, and DNA repair. Although originally identified as gene silencers capable of extending cell lifespan, the involvement of sirtuins in many different areas of cell biology has now become widespread. Our approach has been to study the temporal variation and also the effect of environmental stressors, such as ultraviolet B (UVB) and ozone, on sirtuin expression in human epidermal keratinocytes. In this report, we measured the variation in expression of several sirtuins over time and also show how a low dose of UVB can affect this pattern of expression. Moreover, we correlated these changes to variations in hydrogen peroxide (H2O2) and ATP levels. Our data show significant variations in normal sirtuin expression, which may indicate a generalized response by sirtuins to cell cycle kinetics. These results also demonstrate that sirtuins as a family of molecules are sensitive to UVB-induced disruption and may suggest a new paradigm for determining environmental stress on aging and provide direction for the development of new cosmetic products.

  7. Distribution of lymphatic vessels in normal and arthritic human synovial tissues

    PubMed Central

    Xu, H; Edwards, J; Banerji, S; Prevo, R; Jackson, D; Athanasou, N

    2003-01-01

    Methods: Synovial tissues from 5 normal controls, 14 patients with RA, and 16 patients with OA were studied. Lymphatic vessels were identified by immunohistochemistry using antibodies directed against the lymphatic endothelial hyaluronan receptor (LYVE-1) and recognised blood vessel endothelial markers (factor VIII, CD34, CD31). Results: Lymphatic vessels were found in all zones of the normal, OA, and RA synovial membrane. Few lymphatic vessels were seen in the sublining zone in normal and OA synovium which did not show villous hypertrophy. However, in both RA synovium and OA synovium showing villous hypertrophy and a chronic inflammatory cell infiltrate, numerous lymphatic vessels were seen in all zones of the synovial membrane, including the sublining zone of the superficial subintima. Conclusions: Lymphatic vessels are present in normal and arthritic synovial tissues and are more numerous and prominent where there is oedema and an increase in inflammatory cells in the subintima, particularly in RA. This may reflect increased transport of hyaluronan and leucocyte trafficking in inflamed synovial tissues. PMID:14644866

  8. High burden and pervasive positive selection of somatic mutations in normal human skin

    PubMed Central

    Martincorena, Iñigo; Roshan, Amit; Gerstung, Moritz; Ellis, Peter; Van Loo, Peter; McLaren, Stuart; Wedge, David C.; Fullam, Anthony; Alexandrov, Ludmil B.; Tubio, Jose M.; Stebbings, Lucy; Menzies, Andrew; Widaa, Sara; Stratton, Michael R.; Jones, Philip H.; Campbell, Peter J.

    2015-01-01

    How somatic mutations accumulate in normal cells is central to understanding cancer development, but is poorly understood. We performed ultra-deep sequencing of 74 cancer genes in small (0.8-4.7mm2) biopsies of normal skin. Across 234 biopsies of sun-exposed eyelid epidermis from four individuals, the burden of somatic mutations averaged 2-6 mutations/megabase/cell, similar to many cancers, and exhibited characteristic signatures of ultraviolet light exposure. Remarkably, multiple cancer genes are under strong positive selection even in physiologically normal skin, including most of the key drivers of cutaneous squamous cell carcinomas. Positively selected ‘driver’ mutations were found in 18-32% of normal skin cells at a density of ~140/cm2. We observed variability in the driver landscape among individuals and variability in sizes of clonal expansions across genes. Thus, aged, sun-exposed skin is a patchwork of thousands of evolving clones, with over a quarter of cells carrying cancer-causing mutations while maintaining the physiological functions of epidermis. PMID:25999502

  9. Reciprocal Paracrine Interactions Between Normal Human Epithelial and Mesenchymal Cells Protect Cellular DNA from Radiation-Induced Damage

    SciTech Connect

    Nakazawa, Yuka; Saenko, Vladimir Rogounovitch, Tatiana; Suzuki, Keiji; Mitsutake, Norisato; Matsuse, Michiko; Yamashita, Shunichi

    2008-06-01

    Purpose: To explore whether interactions between normal epithelial and mesenchymal cells can modulate the extent of radiation-induced DNA damage in one or both types of cells. Methods and Materials: Human primary thyrocytes (PT), diploid fibroblasts BJ, MRC-5, and WI-38, normal human mammary epithelial cells (HMEC), and endothelial human umbilical cord vein endothelial cells (HUV-EC-C), cultured either individually or in co-cultures or after conditioned medium transfer, were irradiated with 0.25 to 5 Gy of {gamma}-rays and assayed for the extent of DNA damage. Results: The number of {gamma}-H2AX foci in co-cultures of PT and BJ fibroblasts was approximately 25% lower than in individual cultures at 1 Gy in both types of cells. Reciprocal conditioned medium transfer to individual cultures before irradiation resulted in approximately a 35% reduction of the number {gamma}-H2AX foci at 1 Gy in both types of cells, demonstrating the role of paracrine soluble factors. The DNA-protected state of cells was achieved within 15 min after conditioned medium transfer; it was reproducible and reciprocal in several lines of epithelial cells and fibroblasts, fibroblasts, and endothelial cells but not in epithelial and endothelial cells. Unlike normal cells, human epithelial cancer cells failed to establish DNA-protected states in fibroblasts and vice versa. Conclusions: The results imply the existence of a network of reciprocal interactions between normal epithelial and some types of mesenchymal cells mediated by soluble factors that act in a paracrine manner to protect DNA from genotoxic stress.

  10. Influence of acid and bile acid on ERK activity, PPARγ expression and cell proliferation in normal human esophageal epithelial cells

    PubMed Central

    Jiang, Zhi-Ru; Gong, Jun; Zhang, Zhen-Ni; Qiao, Zhe

    2006-01-01

    AIM: To observe the effects of acid and bile acid exposure on cell proliferation and the expression of extracellular signal-regulated protein kinase (ERK) and peroxisome proliferator-activated receptor γ (PPARγ) in normal human esophageal epithelial cells in vitro. METHODS: In vitro cultured normal human esophageal epithelial cells were exposed to acidic media (pH 4.0 - 6.5), media containing different bile acid (250 μmol/L), media containing acid and bile acid, respectively. Cell proliferation was assessed using MTT and flow cytometry. The expressions of phosphorylated ERK1/2 and PPARγ protein were determined by the immunoblotting technique. RESULTS: Acid-exposed (3 min) esophageal cells exhibited a significant increase in proliferation ratio, S phase of the cell cycle (P < 0.05) and the level of phosphorylated ERK1/2 protein. When the acid-exposure period exceeded 6 min, we observed a decrease in proliferation ratio and S phase of the cell cycle, with an increased apoptosis ratio (P < 0.05). Bile acid exposure (3-12 min) also produced an increase in proliferation ratio, S phase of the cell cycle (P < 0.05) and phosphorylated ERK1/2 expression. On the contrary, deoxycholic acid (DCA) exposure (> 20 min) decreased proliferation ratio. Compared with bile acid exposure (pH 7.4), bile acid exposure (pH 6.5, 4) significantly decreased proliferation ratio (P < 0.05). There was no expression of PPARγ in normal human esophageal epithelial cells. CONCLUSION: The rapid stimuli of acid or bile acid increase proliferation in normal human esophageal epithelial cells by activating the ERK pathway. PMID:16688842

  11. Ex vivo 2D and 3D HSV-2 infection model using human normal vaginal epithelial cells.

    PubMed

    Zhu, Yaqi; Yang, Yan; Guo, Juanjuan; Dai, Ying; Ye, Lina; Qiu, Jianbin; Zeng, Zhihong; Wu, Xiaoting; Xing, Yanmei; Long, Xiang; Wu, Xufeng; Ye, Lin; Wang, Shubin; Li, Hui

    2017-01-27

    Herpes simplex virus type 2 (HSV-2) infects human genital mucosa and establishes life-long latent infection. It is unmet need to establish a human cell-based microphysiological system for virus biology and anti-viral drug discovery. One of barriers is lacking of culture system of normal epithelial cells in vitro over decades. In this study, we established human normal vaginal epithelial cell (HNVEC) culture using co-culture system. HNVEC cells were then propagated rapidly and stably in a defined culture condition. HNVEC cells exhibited a normal diploid karyotype and formed the well-defined and polarized spheres in matrigel three-dimension (3D) culture, while malignant cells (HeLa) formed disorganized and nonpolar solid spheres. HNVEC cells had a normal cellular response to DNA damage and had no transforming property using soft agar assays. HNVEC expressed epithelial marker cytokeratin 14 (CK14) and p63, but not cytokeratin 18 (CK18). Next, we reconstructed HNVEC-derived 3D vaginal epithelium using air-liquid interface (ALI) culture. This 3D vaginal epithelium has the basal and apical layers with expression of epithelial markers as its originated human vaginal tissue. Finally, we established an HSV-2 infection model based on the reconstructed 3D vaginal epithelium. After inoculation of HSV-2 (G strain) at apical layer of the reconstructed 3D vaginal epithelium, we observed obvious pathological effects gradually spreading from the apical layer to basal layer with expression of a viral protein. Thus, we established an ex vivo 2D and 3D HSV-2 infection model that can be used for HSV-2 virology and anti-viral drug discovery.

  12. Normal human mitral valve proteome: A preliminary investigation by gel-based and gel-free proteomic approaches.

    PubMed

    Brioschi, Maura; Baetta, Roberta; Ghilardi, Stefania; Gianazza, Erica; Guarino, Anna; Parolari, Alessandro; Polvani, Gianluca; Tremoli, Elena; Banfi, Cristina

    2016-10-01

    The mitral valve is a highly complex structure which regulates blood flow from the left atrium to the left ventricle (LV) avoiding a significant forward gradient during diastole or regurgitation during systole. The integrity of the mitral valve is also essential for the maintenance of normal LV size, geometry, and function. Significant advances in the comprehension of the biological, functional, and mechanical behavior of the mitral valve have recently been made. However, current knowledge of protein components in the normal human mitral valve is still limited and complicated by the low cellularity of this tissue and the presence of high abundant proteins from the extracellular matrix. We employed here an integrated proteomic approach to analyse the protein composition of the normal human mitral valve and reported confident identification of 422 proteins, some of which have not been previously described in this tissue. In particular, we described the ability of pre-MS separation technique based on liquid-phase IEF and SDS-PAGE to identify the largest number of proteins. We also demonstrated that some of these proteins, e.g. αB-Crystallin, septin-11, four-and-a-half LIM domains protein 1, and dermatopontin, are synthesised by interstitial cells isolated from human mitral valves. These initial results provide a valuable basis for future studies aimed at analysing in depth the mitral valve protein composition and at investigating potential pathogenetic molecular mechanisms. Data are available via ProteomeXchange with identifier PXD004397.

  13. Orofacial inflammatory pain affects the expression of MT1 and NADPH-d in rat caudal spinal trigeminal nucleus and trigeminal ganglion

    PubMed Central

    Huang, Fang; He, Hongwen; Fan, Wenguo; Liu, Yongliang; Zhou, Hongyu; Cheng, Bin

    2013-01-01

    Very little is known about the role of melatonin in the trigeminal system, including the function of melatonin receptor 1. In the present study, adult rats were injected with formaldehyde into the right vibrissae pad to establish a model of orofacial inflammatory pain. The distribution of melatonin receptor 1 and nicotinamide adenine dinucleotide phosphate diaphorase in the caudal spinal trigeminal nucleus and trigeminal ganglion was determined with immunohistochemistry and histochemistry. The results show that there are significant differences in melatonin receptor 1 expression and nicotinamide adenine dinucleotide phosphate diaphorase expression in the trigeminal ganglia and caudal spinal nucleus during the early stage of orofacial inflammatory pain. Our findings suggest that when melatonin receptor 1 expression in the caudal spinal nucleus is significantly reduced, melatonin's regulatory effect on pain is attenuated. PMID:25206619

  14. Denervation of the Eustachian Tube and Hearing Loss Following Trigeminal Schwannoma Resection

    PubMed Central

    Ito, Christopher J.; Malone, Alexander K.; Wong, Ricky H.; van Loveren, Harry R.; Boyev, K. Paul

    2016-01-01

    Objectives To discuss eustachian tube dysfunction (ETD) as a cause of hearing loss and to discuss its pathogenesis following resection of trigeminal schwannomas. Methods Presented herein are two cases of trigeminal schwannoma that were resected surgically with sacrifice of the motor branch of the trigeminal nerve. Neither of the cases had evidence of extracranial extension nor preoperative ETD. Both patients developed ETD and have been followed without evidence of schwannoma recurrence. Conclusions Trigeminal schwannomas are rare tumors that typically require surgical resection. Hearing loss is a potential postsurgical deficit and warrants evaluation by an otolaryngologist with consideration given to a preoperative audiogram. ETD as a result of trigeminal motor branch sacrifice should be included in the differential diagnosis of postoperative hearing loss in this patient subset as it may be reversed with placement of a tympanostomy tube. PMID:26937336

  15. Perineural tumour spread from colon cancer, an unusual cause of trigeminal neuropathy - a case report

    PubMed Central

    Nair, Kavitha; George, Thomas; El Beltagi, Ahmed

    2015-01-01

    Malignant trigeminal neuralgia due to perineural spread along the branches of the trigeminal nerve, is known to commonly occur secondary to squamous cell carcinomas, lymphomas and adenoid cystic carcinomas in the head and neck region. Rarely metastases to the trigeminal nerve have been reported in breast cancer, prostate cancer and colon cancer. To the best of our knowledge trigeminal neuropathy due to skull base metastases and perineural spread along the maxillary (V2) and mandibular (V3) branches of the trigeminal nerve, secondary to colon cancer, has not been previously reported. The diagnosis in our index case was made on magnetic resonance imaging, and patient was treated accordingly by fractionated stereotactic radiotherapy, with subsequent relief of her pain. PMID:26629299

  16. Monitoring of permeability of different analytes in human normal and cancerous bladder tissues in vitro using optical coherence tomography

    SciTech Connect

    Bingsong Lei; Xiaoyuan Deng; Huajiang Wei; Zhouyi Guo; Guoyong Wu; Hongqin Yang; Shusen Xie; Yonghong He

    2014-12-31

    We report our preliminary results on quantification of glucose and dimethyl sulfoxide (DMSO) diffusion in normal and cancerous human bladder tissues in vitro by using a spectral domain optical coherence tomography (SD-OCT). The permeability coefficients (PCs) of a 30% aqueous solution of glucose are found to be (7.92 ± 0.81) × 10{sup -6} cm s{sup -1} and (1.19 ± 0.13) × 10{sup -5} cm s{sup -1} in normal and cancerous bladder tissues, respectively. The PCs of 50% DMSO are calculated to be (8.99 ± 0.93) × 10{sup -6} cm s{sup -1} and (1.43 ± 0.17) × 10{sup -5} cm s{sup -1} in normal and cancerous bladder tissues, respectively. The obtained results show a statistically significant difference in permeability of normal and cancerous tissue and indicate that the PC of 50% DMSO is about 1.13-and 1.21-fold higher than that of 30% glucose in normal bladder and cancerous bladder tissues, respectively. Thus, the quantitative measurements with the help of PCs from OCT images can be a potentially powerful method for bladder cancer detection. (optical coherence tomography)

  17. Three-Dimensionally Engineered Normal Human Broncho-epithelial Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    NASA Technical Reports Server (NTRS)

    Goodwin, T. J.; McCarthy, M.; Lin, Y-H

    2006-01-01

    In vitro three-dimensional (3D) human broncho-epithelial (HBE) tissue-like assemblies (3D HBE TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and parainfluenza virus type 3 (wtPIV3 JS) and the detection of membrane bound glycoproteins over time confirm productive infections with both viruses. Therefore, TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host's immune system.

  18. Three-Dimensionally Engineered Normal Human Lung Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas J.; McCarthy, M.; Lin, Y-H.; Deatly, A. M.

    2008-01-01

    In vitro three-dimensional (3D) human lung epithelio-mesenchymal tissue-like assemblies (3D hLEM TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and the detection of membrane bound glycoproteins over time confirm productive infection with the virus. Therefore, we assert TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host s immune system.

  19. Normal and shear strains of the left ventricle in healthy human subjects measured by two-dimensional speckle tracking echocardiography

    PubMed Central

    2014-01-01

    Background Animal studies have shown that shear deformation of myocardial sheets in transmural planes of left ventricular (LV) wall is an important mechanism for systolic wall thickening, and normal and shear strains of the LV free wall differ from those of the interventricular septum (IVS). We sought to test whether these also hold for human hearts. Methods Thirty healthy volunteers (male 23 and female 7, aged 34 ± 6 years) from Outpatient Department of the University of Tokyo Hospital were included. Echocardiographic images were obtained in the left decubitus position using a commercially available system (Aloka SSD-6500, Japan) equipped with a 3.5-MHz transducer. The ECG was recorded simultaneously. The peak systolic radial normal strain (length change), shear strain (angle change) and time to peak systolic radial normal strain were obtained non-invasively by two-dimensional speckle tracking echocardiography. Results The peak systolic radial normal strain in both IVS and LV posterior wall (LVPW) showed a trend to increase progressively from the apical level to the basal level, especially at short axis views, and the peak systolic radial normal strain of LVPW was significantly greater than that of IVS at all three levels. The time to peak systolic radial normal strain was the shortest at the basal IVS, and increased progressively from the base to the apical IVS. It gradually increased from the apical to the basal LVPW in sequence, especially at short axis views. The peak of radial normal strain of LVPW occurred much later than the peak of IVS at all three levels. For IVS, the shear deformation was clockwise at basal level, and counterclockwise at mid and apical levels in LV long-axis view. For LVPW, the shear deformations were all counterclockwise in LV long-axis view and increased slightly from base to the apex. LVPW showed larger shear strains than IVS at all three levels. Bland-Altman analysis shows very good agreement between measurements taken by the

  20. Diversity in specificity, abundance, and composition of anti-Neu5Gc antibodies in normal humans: Potential implications for disease

    PubMed Central

    Padler-Karavani, Vered; Yu, Hai; Cao, Hongzhi; Chokhawala, Harshal; Karp, Felix; Varki, Nissi; Chen, Xi; Varki, Ajit

    2008-01-01

    Human heterophile antibodies that agglutinate animal erythrocytes are known to detect the nonhuman sialic acid N-glycolylneuraminic acid (Neu5Gc). This monosaccharide cannot by itself fill the binding site (paratope) of an antibody and can also be modified and presented in various linkages, on diverse underlying glycans. Thus, we hypothesized that the human anti-Neu5Gc antibody response is diverse and polyclonal. Here, we use a novel set of natural and chemoenzymatically synthesized glycans to show that normal humans have an abundant and diverse spectrum of such anti-Neu5Gc antibodies, directed against a variety of Neu5Gc-containing epitopes. High sensitivity and specificity assays were achieved by using N-acetylneuraminic acid (Neu5Ac)-containing probes (differing from Neu5Gc by one less oxygen atom) as optimal background controls. The commonest anti-Neu5Gc antibodies are of the IgG class. Moreover, the range of reactivity and Ig classes of antibodies vary greatly amongst normal humans, with some individuals having remarkably large amounts, even surpassing levels of some well-known natural blood group and xenoreactive antibodies. We purified these anti-Neu5Gc antibodies from individual human sera using a newly developed affinity method and showed that they bind to wild-type but not Neu5Gc-deficient mouse tissues. Moreover, they bind back to human carcinomas that have accumulated Neu5Gc in vivo. As dietary Neu5Gc is primarily found in red meat and milk products, we suggest that this ongoing antigen-antibody reaction may generate chronic inflammation, possibly contributing to the high frequency of diet-related carcinomas and other diseases in humans. PMID:18669916

  1. Distinct development of the trigeminal sensory nuclei in platypus and echidna.

    PubMed

    Ashwell, Ken W S; Hardman, Craig D

    2012-01-01

    Both lineages of the modern monotremes have been reported to be capable of electroreception using the trigeminal pathways and it has been argued that electroreception arose in an aquatic platypus-like ancestor of both modern monotreme groups. On the other hand, the trigeminal sensory nuclear complex of the platypus is highly modified for processing tactile and electrosensory information from the bill, whereas the trigeminal sensory nuclear complex of the short-beaked echidna (Tachyglossus aculeatus) is not particularly specialized. If the common ancestor for both platypus and echidna were an electroreceptively and trigeminally specialized aquatic feeder, one would expect the early stages of development of the trigeminal sensory nuclei in both species to show evidence of structural specialization from the outset. To determine whether this is the case, we examined the development of the trigeminal sensory nuclei in the platypus and short-beaked echidna using the Hill and Hubrecht embryological collections. We found that the highly specialized features of the platypus trigeminal sensory nuclei (i.e. the large size of the principal nucleus and oral part of the spinal trigeminal nuclear complex, and the presence of a dorsolateral parvicellular segment in the principal nucleus) appear around the time of hatching in the platypus, but are never seen at any stage in the echidna. Our findings support the proposition that the modern echidna and platypus are derived from a common ancestor with only minimal trigeminal specialization and that the peculiar anatomy of the trigeminal sensory nuclei in the modern platypus emerged in the ornithorhynchids after divergence from the tachyglossids.

  2. Portrayal of pheochromocytoma and normal human adrenal medulla by m-(123I)iodobenzylguanidine: concise communication

    SciTech Connect

    Lynn, M.D.; Shapiro, B.; Sisson, J.C.; Swanson, D.P.; Mangner, T.J.; Wieland, D.M.; Meyers, L.J.; Glowniak, J.V.; Beierwaltes, W.H.

    1984-04-01

    The radiopharmaceutical m-(131I)iodobenzylguanidine (I-131 MIBG), which is readily taken up by adrenergic vesicles, produces scintigraphic images of pheochromocytomas in man but rarely visualizes normal adrenal glands. Iodine-123 has many potential advantages over I-131 as a radiolabel for MIBG, including shorter half-life, freedom from beta emissions, and increased gamma-camera efficiency. In this study, diagnostic doses of MIBG labeled with I-131 and I-123, with nearly equivalent radiation dosimetry, were compared as imaging agents in eight patients with known or suspected pheochromocytoma. Images of superior quality were obtained with I-123 MIBG, and lesions not visualized using I-131 MIBG were portrayed. In addition, the normal adrenal medullae were visualized on the I-123 MIBG scintigrams in six out of eight patients.

  3. Human placental insulin binding in normal and well-controlled diabetic patients.

    PubMed

    Nelson, D M; Ortman-Nabi, J; Curran, E M

    1990-01-01

    Previous studies of insulin binding to placentas of both insulin-dependent and untreated gestational diabetic patients have described placentas from diabetics to contain fewer insulin receptors than placentas from nondiabetic gravidas. However, these studies were done using membrane fractions prepared from the placentas and at a time when adequacy of antepartum glycemic control in the diabetic patients was not routinely evaluated by self blood sugar measurement or hemoglobin A1 assay. The current study compares specific 125I-insulin binding in vitro to intact placental villi from 15 normal patients with insulin binding to intact villi obtained from 15 insulin-dependent diabetic mothers whose fasting and postprandial blood sugars and hemoglobin A1 levels were maintained in a range normal for term pregnancy. We demonstrate that insulin binding to intact placental villi is the same in this group of diabetic patients as in the nondiabetic patients.

  4. Improved technique for measuring fecal energy loss in normal and malabsorbing humans.

    PubMed

    Zarling, E J; Ruchim, M A; Makino, D

    1986-01-01

    Fecal energy concentration is measured by bomb calorimetry on freeze-dried stool samples. Some of the energy-containing fecal compounds are volatile in the pH ranges of normal stool and hence may be lost during sample preparation. We found that significant amounts of volatile fatty acids and lactic acid are lost during lyophilization. Fecal alkalization caused an increase of 9.8% of measurable energy in stools from normal individuals and 25% in stools from patients with untreated exocrine pancreatic insufficiency. We conclude that previous reports of fecal energy concentr