Activated Transcription of the Human Neuropeptide Y Gene in Differentiating SH-SY5Y Neuroblastoma Cells Is Dependent on Transcription Factors AP-1, AP-2Α, and NGFI

Activated transcription of the human neuropeptide Y gene ( NPY ) was investigated in SH-SY5Y neuroblastoma cells at the onset of sympathetic neuronal differentiation induced by 12- O -tetradecanoylphorbol 13-acetate (TPA) and serum or by nerve growth factor (NGF). As determined by transient expression, two NGF response elements (REs) were required for transcription induced by NGF in SH-SY5Y cells with stable expression of an exogenous NGF receptor TRK-A gene (SH-SY5Y/trk). TPA treatment in the presence of serum induced NPY transcription in both wild-type SH-SY5Y (SH-SY5Y/wt) and SH-SY5Y/trk cells. A TPA RE (TRE), overlapping the proximal NGF RE, was identified by expression of the v-Jun oncoprotein that enhanced NPY transcription. Suppression of TPA-induced NPY transcription was obtained by expression of a dominant negative Jun protein, selective protein kinase C inhibition, or introduction of a mutated TRE, whereas NGF-induced NPY transcription was inhibited to a lesser degree. The transcription factor AP-2Α was shown to bind cooperatively to the NPY promoter with either AP-1 or NGFI-A to the shared TRE and NGF RE and to the distal NGF RE, respectively. These results show that transcription factors AP-1, AP-2Α, and NGFI-A are involved in activated NPY transcription during the onset of neuronal differentiation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65864/1/j.1471-4159.1998.70051887.x.pd

Systemic and targeted delivery of semaphorin 3A inhibits tumor angiogenesis and progression in mouse tumor models

The role of semaphorins in tumor progression is still poorly understood. In this study, we aimed at elucidating the regulatory role of semaphorin 3A (SEMA3A) in primary tumor growth and metastatic dissemination

Toimenpidepotilaiden kokemuksia leikkaussalissa tapahtuvan hoitotyön turvallisuudesta

Länsi-Pohjan keskussairaalan leikkaus- ja anestesiaosastolla otettiin vuonna 2010 käyttöön leikkaustoiminnan tarkistuslista potilasturvallisuutta varmistamaan. Opinnäytetyön tarkoituksena oli kartoittaa toimenpidepotilaiden kokemuksia hoitotyön turvallisuudesta intraoperatiivisessa vaiheessa. Tutkimuksen tavoitteena oli potilaiden näkökulmasta tuotetun tiedon avulla kehittää perioperatiivisen hoitotyön laatua ja lisätä tietoisuutta potilasturvallisuutta vaarantavista sekä edistävistä tekijöistä. Tutkimuskohteena olivat aikuiset toimenpidepotilaat. Tutkimuksessa keskityttiin leikkauksen aikaiseen vaiheeseen ja tutkimuskohde rajattiin puudutettuihin aikuispotilaisiin, koska he pystyvät seuraamaan turvallisuuden toteutumista toimenpiteen aikana. Tutkimuksessa käytettiin mittarina kyselylomaketta, jolla kartoitettiin aikuispotilaiden kokemuksia toimenpiteen aikana. Kvantitatiivinen surveytutkimus tehtiin ryväsotannalla toukokuussa 2011. Toimenpidepotilaat, joilla oli aikaisempia leikkauskokemuksia pelkäsivät enemmän toimenpidettä kuin potilaat joilla ei ollut aikaisempia leikkauskokemuksia. Kaikki potilaat tiesivät ennakolta, millainen toimenpide heille oli suunniteltu tehtäväksi. Potilaat olivat saaneet ohjausta ennen toimenpidettä selkeällä ja ymmärrettävällä kielellä ja heitä pidettiin ajan tasalla toimenpiteen kulusta. Henkilökunnan työskentely oli ystävällistä ja rauhallista. Henkilökunta esittäytyi potilaalle ja kysyi potilaan vointia toimenpiteen aikana. Potilaat tunsivat olonsa turvalliseksi toimenpiteen aikana ja he saivat kipulääkettä. Kipulääkityksestä huolimatta lähes puolet vastaajista olivat olleet kipeitä leikkauksen jälkeen. Potilaiden mielestä joitakin anestesia- ja leikkausturvallisuuteen liittyviä kohtia ei tarkistettu riittävästi. Käytännön hoitotyössä lyhentyneet hoitoajat ja tehokkusvaatimus luovat haasteita potilaan ohjaukselle. Luottamuksellisen suhteen luominen potilaaseen edellyttää hyviä vuorovaikutustaitoja, joita opitaan käytännön hoitotyössä ja itsensä kehittämisellä.In 2010 the operating room at Central Hospital of Kemi had started to use the Surgical Safety Checklist for benefit patient safety. The purpose of this thesis was to investigate patient’s experiences of safety during the intraoperative care. The objective of this thesis was to identify from the patients’ perspective areas for quality improvement during intraoperative care. Research subjects were adult patients. The study concentrated on the surgical stage and limited to numbed patients because they are awake and able to follow the implementation of safety during the operation. Questionnaire surveyed the patients experience during the procedure. The quantitative survey study was carried as a cluster sample in May 2011. Patients with previous surgical experience feared more the procedure than the patients who had no previous surgical experiences. All patients knew their elective surgery. Patients had received counseling before the procedure in a clear and understandable language, and they were kept informed throughout the operation. The staff worked friendly, calmly, and they introduced themselves to the patient and asked the patient's condition during the operation. Patients felt safe and comfortable, and they get pain medication, but in spite of the analgesic nearly half of the patients were painful after the surgery. Patents considered that some of anesthesia and surgical safety items were not checked enough. Shorter treatment times and efficiency in the health care challenges the patient’s guiding. Confidential relationship with the patients requires good communication skills, which are learned in practice and self education

Human achaete-scute homologue 1 (HASH-1) is downregulated in differentiating neuroblastoma cells

The mammalian achaete-scute homologue, MASH-1, is crucial for early development of the sympathetic nervous system and is transiently expressed in sympathetic neuroblasts during embryogenesis. Here we report that the human homologue (HASH-1) was expressed in all analyzed cell lines (6/6) derived from the sympathetic nervous system tumor neuroblastoma. The majority of small-cell lung carcinoma (4/5) cell lines tested expressed HASH-1, while other nonneuronal/non-neuroendocrine cell lines were negative. Induced differentiation of neuroblastoma cells resulted in HASH-1 downregulation. This occurred concomitant with induction of neurite outgrowth and expression of the neuronal marker genes GAP-43 and neuropeptide Y. Constitutive expression of exogenous HASH-1 did not alter the capacity of the neuroblastoma cells to differentiate in response to differentiation-inducing agents. It is concluded that moderate HASH-1 expression does not compromise the capacity of these cells to differentiate

HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF

Polarization of tumor-associated macrophages (TAMs) to a proangiogenic/immune-suppressive (M2-like) phenotype and abnormal, hypoperfused vessels are hallmarks of malignancy, but their molecular basis and interrelationship remains enigmatic. We report that the host-produced histidine-rich glycoprotein (HRG) inhibits tumor growth and metastasis, while improving chemotherapy. By skewing TAM polarization away from the M2- to a tumor-inhibiting M1-like phenotype, HRG promotes antitumor immune responses and vessel normalization, effects known to decrease tumor growth and metastasis and to enhance chemotherapy. Skewing of TAM polarization by HRG relies substantially on downregulation of placental growth factor (PlGF). Besides unveiling an important role for TAM polarization in tumor vessel abnormalization, and its regulation by HRG/PlGF, these findings offer therapeutic opportunities for anticancer and antiangiogenic treatment