bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional expression of the serotonin 5‐HT7 receptor in human glioblastoma cell lines
Authors: Mahé Cécile , Bernhard Michel , Bobirnac Ionel , Keser Corinna , Loetscher Erika , Feuerbach Dominik , Dev Kumlesh K , Schoeffter Philippe 
Published: October 2004

Serotonin 5‐HT7 receptors are present in astrocytes. Understanding their role in this type of cell would greatly benefit from the identification of astroglial cell lines expressing this receptor type.
The aim of the present study was to assess the expression of native 5‐HT7 receptors and 5‐HT7 receptor mRNA in a number of human glioblastoma cell lines, by means of cAMP measurements, Western blot analysis and reverse transcriptase–polymerase chain reaction (RT–PCR) analysis.
5‐Hydroxytryptamine (5‐HT), 5‐carboxamidotryptamine (5‐CT), 5‐methoxytryptamine (5‐MeOT) and 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT) induced concentration‐dependent stimulations of cAMP accumulation in the human glioblastoma cell lines, U‐373 MG, U‐138 MG, U‐87 MG, DBTRG‐05MG, T98G, H4, CCF‐STTG1 and Hs 683. The rank order of potency was 5‐CT>5‐HT=5‐MeOT≫8‐OH‐DPAT.
The effect of 5‐CT was inhibited in a concentration‐dependent manner by the selective 5‐HT7 receptor antagonist SB‐269970 in all human glioblastoma cells. Schild analyses yielded slope factors close to unity (0.89–1.13) and pA2 values of 8.69–9.05.
Western blot analysis revealed the presence of immunoreactive bands corresponding to the human 5‐HT7 receptor in extracts of all human glioblastoma cell lines.
The presence of the three splice variants of the 5‐HT7 receptor (5‐HT7(a/b/d)) was visualized by RT–PCR analysis with specific primers in all human glioblastoma cell lines.
In conclusion, human glioblastoma cell lines express functional 5‐HT7 receptors and the three splice variants of the corresponding mRNA. These cell lines could serve as model systems of native 5‐HT7 receptors in glial cells to investigate their putative role in processes like release of neurotrophic factors or inflammatory cytokines.

British Journal of Pharmacology (2004) 143, 404–410. doi:10.1038/sj.bjp.0705936
Alterations in glucose metabolism by cyclosporine in rat brain slices link to oxidative stress: interactions with mTOR inhibitors
Authors: Christians Uwe , Gottschalk Sven , Miljus Jelena , Hainz Carsten , Benet Leslie Z , Leibfritz Dieter , Serkova Natalie 
Published: October 2004

Co‐administration of the calcineurin inhibitor cyclosporine and the mTOR inhibitors sirolimus or everolimus increases the efficacy of immunosuppression after organ transplantation. However, clinical studies showed enhancement of cyclosporine toxicity. To characterize the biochemical mechanisms involved, we assessed the time‐dependent effects of cyclosporine in combination with mTOR inhibitors on energy production (ex vivo 31P‐MRS), glucose metabolism (ex vivo 13C‐MRS), and reactive oxygen species (ROS) formation (using the fluorescent agent 2′,7′‐dichlorofluorescein diacetate) in perfused rat brain slices.
Cyclosporine alone inhibited energy production (ATP: 75±9%), the Krebs cycle (4‐13C‐glutamate from 1‐13C‐glucose: 61±27%), and oxidative phosphorylation (NAD+: 62±25%) after 4 h of perfusion. After 10 h, activation of anaerobic glycolysis (3‐13C‐lactate: 140±17%) compensated for inhibition of mitochondrial energy production and lowered the intracellular pH. ROS formation was increased after 4 h (285±55% of untreated control), but not after 10 h. mTOR inhibitors alone inhibited lactate production. When combined with cyclosporine, sirolimus enhanced cyclosporine‐induced inhibition of energy metabolism (ATP: 64±9%) and ROS formation (367±46%). Most importantly, sirolimus inhibited cytosolic glycolysis and therefore compensation for cyclosporine‐induced ATP reduction after 10 h. In contrast to sirolimus, everolimus antagonized cyclosporine‐induced inhibition of mitochondrial energy metabolism (ATP: 91±7%) and ROS formation (170±49%). The antioxidant tocopherol antagonized all cyclosporine effects on cell metabolism.
Cyclosporine time‐dependently inhibited mitochondrial metabolism and increased ROS, followed by compensation involving anaerobic glycolysis. Everolimus antagonized cyclosporine‐induced mitochondrial dysfunction, whereas sirolimus inhibited compensatory anaerobic glycolysis, thus enhancing cyclosporine's negative effects. ROS play the key role in mediating the negative effects of cyclosporine on cell energy metabolism.

British Journal of Pharmacology (2004) 143, 388–396. doi:10.1038/sj.bjp.0705939
Bolus injection of human UII in conscious rats evokes a biphasic haemodynamic response
Authors: Gardiner Sheila M , March Julie E , Kemp Philip A , Bennett Terence 
Published: October 2004

A biphasic cardiovascular response to bolus i.v. injection of human urotensin II (hUII, 3 nmol kg−1) in conscious, male, Sprague–Dawley (SD) rats was identified and underlying mechanisms were explored. Initially (0–5 min) there was tachycardia, hypotension and mesenteric and hindquarters vasodilatation; later (30–120 min), tachycardia, hindquarters vasodilatation and a modest rise in blood pressure occurred.
Pretreatment with indomethacin or NG nitro‐L‐arginine methylester (L‐NAME) reduced the mesenteric vasodilator response to hUII, and abolished the late tachycardia and hindquarters vasodilatation. Indomethacin also abolished the hypotension and early hindquarters vasodilatation, and substantially reduced the initial tachycardia. Indomethacin and L‐NAME together prevented all haemodynamic responses to hUII.
Inhibition of inducible NOS had no effect on responses to hUII, whereas inhibition of neuronal NOS reduced the delayed tachycardic response to hUII but did not significantly affect the vasodilatation. Only the initial tachycardic response to hUII was antagonised by propranolol.
In spontaneously hypertensive rats (SHR), the initial haemodynamic responses to hUII were qualitatively similar to those in SD rats, although there was also a modest renal vasodilatation. The secondary response comprised a smaller tachycardia and a small rise in blood pressure, with no significant hindquarters vasodilatation.
Haemodynamic responses to hUII were not enhanced by endothelin and angiotensin receptor antagonism in either SD rats or in SHRs.
One interpretation of these results is that the primary response to bolus injection of hUII is prostanoid‐ or prostanoid‐ and NO‐mediated (mesenteric vasodilatation) and that this triggers secondary events, which are dependent on eNOS (hindquarters vasodilatation) and neuronal NOS (tachycardia).

British Journal of Pharmacology (2004) 143, 422–430. doi:10.1038/sj.bjp.0705954
High resolution CO2 interferometry on the TJ-II stellarator by using an ADC-based phase meter
Authors: Sánchez M. , Sánchez J. , Estrada T. , Sánchez E. , Acedo P. , Lamela H. 
Published: October 2004

A 10 MSample/s analog-to-digital converter has been used to analyze the signals from the double wavelength heterodyne interferometer (CO2 10.6 μm, HeNe   0.63   μm) in the TJ-II stellarator. The phase difference between the two interferometers has been calculated using a new algorithm in Labview environment. A systematic study of the 1 MHz intermediate frequency has been done using our software and Labview tools. Different sources of noise and nonlinear effects have been analyzed. Crosstalk (from the reference path) has been detected and corrected by software.
The complete system (single channel double pass) has been routinely working during the complete TJ-II autumn experimental campaign, providing the plasma line integral density in scenarious with average densities ranging from few 1018 m−3 to more than 5×1019 m−3. The results have been compared with those from a 2 mm interferometer, obtaining an excellent agreement. Working with a final bandwidth of 4 kHz, a one pass line integral error level about ±−2×1017 m−2 has been achieved.
Bank Loan Availability and Trade Credit Demand
Authors: Danielson Morris G. , Scott Jonathan A. 
Published: October 2004

AbstractThis paper investigates the effects of bank loan availability on the trade credit and credit card demand of small firms, using firm‐level data from the 1995 Credit, Banks, and Small Business Survey, conducted by the National Federation of Independent Business. We find that firms increase their demand for trade credit and credit card debt when facing credit constraints imposed by banks. These results provide evidence of a pecking order of debt financing, where firms increase their reliance on potentially expensive sources of funds when bank loans are not available.
Cyclic Adenosine Monophosphate Inhibits Quinolone Alkaloid Evocarpine‐Induced Apoptosis via Activation of Protein Kinase A in Human Leukaemic HL‐60 Cells
Authors: Kim Na‐Young , Pae Hyun‐Ock , Kang Tai‐Hyun , Kim Youn‐Chul , Lee Ho‐Sub , Chung Hun‐Taeg 
Published: October 2004

Abstract:Evocarpine, an isoquinolone alkaloid isolated from the fruit of Evodia rutaecarpa, was found to induce apoptotic cell death in promyelocytic leukaemia HL‐60 cells in dose‐ and time‐dependent manners. We investigated the involvement of protein kinase A during the evocarpine‐induced apoptotic cell death. Evocarpine‐induced apoptosis was markedly inhibited by treatment of the cells with dibutyryl‐cyclic adenosine monophosphate. Similar results were obtained with other commonly used cyclic adenosine monophosphate analogues, chlorophenylthio‐cyclic adenosine monophosphate and the intracellular cyclic adenosine monophosphate‐elevating agent, forskolin. In contrast, pretreatment of HL‐60 cells with KT5720, an inhibitor of cyclic adenosine monophosphate‐dependent protein kinase A, abrogated the protective effects of cyclic adenosine monophosphate analogues and forskolin on evocrpine‐induced apoptosis. These findings suggest that cyclic adenosine monophosphate‐dependent activation of protein kinase A plays a crucial role in protecting HL‐60 cells from the evocarpine‐induced apoptotic cell death.
Chlorpyrifos‐Induced Hypothermia and Vasodilation in the Tail of the Rat: Blockade by Scopolamine
Authors: Gordon Christopher J. , Yang Yong‐Lu 
Published: October 2004

Abstract:Organophosphate pesticides such as chlorpyrifos reduce core temperature (Tc) in laboratory rodents. The mechanism(s) responsible for the chlorpyrifos‐induced hypothermia are not well known. This study assessed the role of a key effector for thermoregulation in the rat, vasomotor control of heat loss from the tail, and its possible cholinergic control during chlorpyrifos‐induced hypothermia. Tc and motor activity were monitored by telemetry in female Long‐Evans rats maintained at an ambient temperature (Ta) of 25°. Tail skin temperature (Tsk(t)) was measured hourly. Rats were dosed with chlorpyrifos (0 or 25 mg/kg orally). Two hr later the rats were dosed with saline or scopolamine (1.0 mg/kg intraperitoneally). Two hr after chlorpyrifos treatment there was a marked elevation in Tsk(t) concomitant with a 0.5° reduction in Tc. Scopolamine administered to control rats led to a marked elevation in Tc with little change in Tsk(t). Rats treated with chlorpyrifos and administered scopolamine underwent a marked vasoconstriction and elevation in Tc. Vasodilation of the tail is an important thermoeffector to reduce Tc during the acute stages of chlorpyrifos exposure. The blockade of the response by scopolamine suggests that the hypothermic and vasodilatory response to chlorpyrifos is mediated via a cholinergic muscarinic pathway in the CNS.
Four Weeks' Inhalation Exposure of Long Evans Rats to 4‐tert‐Butyltoluene: Effect on Evoked Potentials, Behaviour, and Brain Neurochemistry
Authors: Lam Henrik Rye , Ladefoged Ole , Østergaard Grete , Hass Ulla , Lund Søren Peter , Simonsen Leif 
Published: October 2004

Abstract:Long‐lasting central nervous system (CNS) neurotoxicity of 4‐tert‐butyltoluene (TBT) has been investigated using electrophysiology, behaviour, and neurochemistry in Long Evans rats exposed by inhalation to 0, 20, or 40 p.p.m. TBT 6 hr/day, 7 days/week for 4 weeks. Flash evoked potentials and somatosensory evoked potentials were not affected by TBT. In Auditory Brain Stem Response there was no shift in hearing threshold, but the amplitude of the first wave was increased in both exposed groups at high stimulus levels. Three to four months after the end of exposure, behavioural studies in Morris water maze and eight‐arm maze failed to demonstrate any TBT induced effects. Exposure was followed by a 5 months exposure‐free period prior to gross regional and subcellular (synaptosomal) neurochemical investigations of the brain. TBT reduced the NA concentration in whole brain minus cerebellum. Synaptosomal choline acetyltransferase activity increased and acetylcholinesterase activity was unchanged suggesting increased synaptosomal ability for acetylcholine synthesis. The relative and total yield of synaptosomal protein was reduced suggesting reduced density and total number of synapses in situ, respectively. We hypothesise that a reduced yield of synaptosomal protein reflects a more general effect of organic solvent exposure on the software of the brain. The synaptosomal concentration per mg synaptosomal protein and the total amount of 5‐hydroxytryptamine were not affected whereas the total amount of synaptosomal noradrenaline decreased. The concentration and the total amount of synaptosomal dopamine decreased. The noradrenergic and dopaminergic parts of CNS may be more vulnerable to TBT than the serotonergic, and these long‐lasting effects may cause or reflect TBT‐compromised CNS function.
Effects of Apocynin and Natural Antioxidant from Spinach on Inducible Nitric Oxide Synthase and Cyclooxygenase‐2 Induction in Lipopolysaccharide‐Induced Hepatic Injury in Rat
Authors: Lomnitski Liat , Foley Julie F. , Grossman Shlomo , Shaul Varda Ben , Maronpot Robert R. , Moomaw Cindy R. , Carbonatto Michela , Nyska Abraham 
Published: October 2004

Abstract:The immunoreactivity of inducible nitric oxide synthase, and cyclooxygenase‐2 was compared among groups of male Wistar rats comprising those injected with lipopolysaccharide following pretreatment with either natural antioxidant from spinach or the antioxidant apocynin, with lipopolysaccharide without pretreatment with antioxidants, with each of the two antioxidants alone, and untreated controls. The grade of staining of both inducible nitric oxide synthase and cyclooxygenase‐2 increased with the severity of the inflammatory reaction in the lipopolysaccharide‐treated animals, compared to the antioxidant‐treated groups. Interpretation of the results of the immunostained tissues indicated that pretreatment with either antioxidant significantly (P<0.05) attenuated the lipopolysaccharide‐stimulated inducible nitric oxide synthase induction. Analysis of the cycloxygenase‐2‐stained liver samples indicated that the pretreatment with the natural antioxidant NAO significantly (P<0.05) attenuated lipopolysaccharide‐stimulated cycloxygenase‐2 induction; whereas, in animals pretreated with apocynin, there was a trend of reduction in the cyclooxygenase‐2 expression, but not statistically significant (P>0.05). The negative nitrotyrosine immunoreactivity of the lipopolysaccharide‐related hepatic lesions may indicate that there was relatively low interaction between superoxide anions and nitric oxide to form peroxynitrite or that the expression levels of the nitrotyrosine were below the limit of detection. In all treatment groups a positive correlation (P<0.05, r=0.86) found between the inducible nitric oxide synthase and cyclooxygenase‐2 scores suggests a strong relationship between these two parameters. The results indicate the possible therapeutic efficacy of NAO and apocynin in the prevention of liver damage related to clinical endotoxemia known to be associated with oxidative stress.
Day case management of sickle pain: 3 years experience in a UK sickle cell unit
Authors: Wright J. , Bareford D. , Wright C. , Augustine G. , Olley K. , Musamadi L , Dhanda C. , Knight C. 
Published: October 2004

SummaryA day centre was established to determine whether an alternative approach to the management of uncomplicated sickle pain would improve the quality of care and reduce hospital admissions in patients with sickle cell disease. Since the centre opened there has been a 43% decrease in hospital admissions and 49% decrease in occupied bed days. In the third year, 84% of patients treated for severe sickle pain were managed without the need for hospital admission. A centre offering day case management of painful crisis reduced unnecessary hospital admissions for uncomplicated pain. This approach is safe and cost‐effective.
Induction of acute graft‐versus‐host disease by T cells that do not respond to in vitro alloantigen stimulation
Authors: New Jen Yan , Chan Soh Ha , Yap Eu Hian , Hu Huaizhong 
Published: October 2004

SummaryThe mixed lymphocyte reaction (MLR) has been used extensively to measure alloreactive T cells. In clinical practice, a negative MLR of recipient T cells responding to donor cells does not necessarily mean that a donor‐specific tolerance has been established. This discrepancy indicates that the presently used methods fail to demonstrate the full repertoire of alloreactive T cells. This could be the result of the fact that some alloreactive T cells do not respond in vitro but will mount a response towards alloantigens in vivo, or that some alloreactive T cells do not respond during the MLR but will respond later if the alloantigen stimulation remains. We therefore examined the non‐proliferating T‐cell population in a mouse primary alloreactive response. Spleen and lymph node cells derived from C57BL/6J (H‐2b) mice were stained with carboxy‐fluorescein diacetate succinimidyl ester and injected intravenously into C.B‐17 severe combined immunodeficient (SCID) mice (H‐2d). The donor cells were recovered 5 d after the injection. The non‐proliferating T cells were sorted and were non‐reactive to alloantigen stimulation in vitro. Nevertheless, these non‐proliferating T cells could proliferate and cause acute graft‐versus‐host disease after being adoptively transferred to secondary recipients of SCID mice. These results suggest that there exists an alloreactive T‐cell population that does not respond to in vitro alloantigen stimulation but can mount a delayed alloresponse in vivo.
Targeted pretransplant host lymphocyte depletion prior to T‐cell depleted reduced‐intensity allogeneic stem cell transplantation
Authors: Bishop Michael R. , Steinberg Seth M. , Gress Ronald E. , Hardy Nancy M. , Marchigiani Donna , Kasten‐Sportes Claude , Dean Robert , Pavletic Steven Z. , Gea‐Banacloche Juan , Castro Kathleen , Hakim Fran , Krumlauf Michael , Read Elizabeth J. , Carter Charles , Leitman Susan F. , Fowler Daniel H. 
Published: October 2004

SummaryMixed chimaerism and graft rejection are higher after reduced‐intensity allogeneic stem cell transplantation (RIST) with T‐cell depleted (TCD) allografts. As host immune status before RIST affects engraftment, we hypothesized that targeted depletion of host lymphocytes prior to RIST would abrogate graft rejection and promote donor chimaerism. Lymphocyte‐depleting chemotherapy was administered at conventional doses to subjects prior to RIST with the intent of decreasing CD4+ counts to <0·05 × 109cells/l. Subjects (n = 18) then received reduced‐intensity conditioning followed by ex vivo TCD human leucocyte antigen‐matched sibling allografts. All evaluable patients (n = 17) were engrafted; there were no late graft failures. At day +28 post‐RIST, 12 patients showed complete donor chimaerism. Mixed chimaerism in the remaining five patients was associated with higher numbers of circulating host CD3+ cells (P = 0·0032) after lymphocyte‐depleting chemotherapy and was preferentially observed in T lymphoid rather than myeloid cells. Full donor chimaerism was achieved in all patients after planned donor lymphocyte infusions. These data reflect the importance of host immune status prior to RIST and suggest that targeted host lymphocyte depletion facilitates the engraftment of TCD allografts. Targeted lymphocyte depletion may permit an individualized approach to conditioning based on host immune status prior to RIST.
IL‐7 effect on immunological reconstitution after HSCT depends on MHC incompatibility
Authors: André‐Schmutz Isabelle , Bonhomme Delphine , Yates Frank , Malassis Michèle , Selz Françoise , Fischer Alain , Cavazzana‐Calvo Marina 
Published: October 2004

SummaryConsiderable progress has been recently accomplished in the management of patients who have undergone haplo‐incompatible haematopoietic stem cell transplantation (HSCT) in terms of intake and prevention of graft‐versus‐host disease. Nevertheless haplo‐incompatible HSCT is a procedure limited to a small number of patients because of the long‐lasting immunodeficiency that is responsible for more than 50% of deaths within the first 3 months. Interleukin (IL)‐7, which plays a unique and key role in T‐cell development both in the mouse and in the human, is particularly attractive for attempting to speed up T‐cell reconstitution. However, controversial results have been obtained after bone marrow graft in murine and primate models. To elucidate the impact of IL‐7 treatment, we have performed HSCT in irradiated murine recombination activating gene (RAG) immunodeficient recipients, using donors that exhibited increased major histocompatibilty complex (MHC) incompatibility. Although irradiation performed prior to HSCT lead to a profound defect in the thymic stromal cells responsible for IL‐7 production, IL‐7 treatment had no significant effect on immune reconstitution in the MHC compatible and partially compatible settings. Interestingly, in the MHC fully incompatible setting in which only one‐third of the recipients demonstrated active thymopoiesis, probably because of the rejection of donor cells by host natural killer cells, IL‐7 treatment had a beneficial effect on T‐cell development.
Prospective clinical evaluation of lower cut‐offs for galactomannan detection in adult neutropenic cancer patients and haematological stem cell transplant recipients
Authors: Maertens Johan , Theunissen Koen , Verbeken Eric , Lagrou Katrien , Verhaegen Jan , Boogaerts Marc , Eldere Johan Van 
Published: October 2004

SummaryThe recent advent of an improved commercial serum enzyme‐linked immunosorbent assay (ELISA) for the detection of circulating galactomannan (GM), a major constituent of Aspergillus cell walls, has contributed to the diagnosis of invasive aspergillosis (IA) in many haematology and transplant centres. However, the optimal threshold for positivity remains a matter of debate. We prospectively evaluated the impact of lowering the cut‐off in 124 neutropenic episodes with a high pretest probability for IA. Two new cut‐off points, lower than previously accepted, are proposed: (a) a ‘static’ cut‐off at 0·8 and (b) a ‘dynamic’ cut‐off at 0·5. A single assay with an optical density (OD) index ≥0·8 warrants the initiation of anti‐Aspergillus therapy. A further lowering of the ‘static’ threshold seems not clinically feasible given the drop in positive predictive value (PPV). However, the demonstration of at least two sequential sera with an OD ≥0·5 (‘dynamic’ threshold) increased the specificity and the PPV to 98·6% and the efficiency to 98%. Applying both cut‐offs to a subgroup of 21 ‘possible’ fungal infections further identified and upgraded six cases of IA. However, the clinical benefit of lower cut‐offs (particularly for earlier diagnosis) depends upon the kinetics of antigenaemia and the intensity of serum sampling.