bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous Blockade of Two Glutamate Receptor Subtypes (NMDA and AMPA) Results in Stressor-Specific Inhibition of Prolactin and Corticotropin Release
Authors: Zelena Dóra , Makara Gábor B. , Jezova Daniela 
Published: April 2003

Many neurons express simultaneously two or more isotypes of glutamate receptors, so that pharmacological modulation of more than one receptor may be necessary to reveal the role of glutamate in mediating physiological processes. The present studies were aimed at evaluating involvement of endogenous glutamate in triggering plasma prolactin (PRL) and adrenocorticotropic hormone (ACTH) levels in response to three different stress stimuli (footshock, immobilization and ether stress). Blockade of glutamate receptor subtypes was achieved by the administration of the NMDA antagonist dizocilpine (MK-801, 0.2 mg/kg) and the selective AMPA antagonist GYKI 52466 (10 mg/kg). Rats were pretreated for 4–5 days and then exposed to stressful stimulation. Basal hormone levels were not affected by the antagonists. In male rats, combined, but not separate blockade of NMDA and AMPA/kainate subtypes of glutamate receptors prevented the rise in plasma PRL in response to footshock stress. In female rats, footshock-induced PRL release was inhibited even by separate blockade of NMDA receptors by dizocilpine, suggesting that the PRL system of females is more sensitive to the effect of NMDA antagonists than that of males. None of the treatments affected PRL release during immobilization or ether stress. Simultaneous blockade of NMDA and AMPA receptor subtypes resulted in a mild inhibition of immobilization-induced ACTH release without any effect on ACTH response to footshock or ether stress. The data suggest that involvement of glutamatergic pathways in neuroendocrine response during stress is selective for discrete stress stimuli and stress hormones. In addition a concerted action of glutamate on both NMDA and non-NMDA receptor subtypes is involved in the control of PRL release during footshock stress.
Animal Study on the Effects of Catalin on Aftercataract and Posterior Capsule Opacification
Authors: Biswas Nihar R. , Mongre Praveen K. , Das Gopal K. , Sen Seema , Angra Surinder K. , Vajpayee Rasik B. 
Published: April 2003

<i>Purpose:</i> To find out the role of Catalin in the prevention of posterior capsular opacification (PCO), we undertook this experimental study in rabbits. <i>Methods:</i> Twenty rabbits (10 for the Catalin group and 10 for the placebo group) were operated on for extracapsular clear lens extraction in an aseptic environment. In all cases, capsulorrhexis of 8 mm diameter was carried out. Both the test drug and placebo were given at a dose of 4 times/day from the first postoperative day for 8 weeks. Common drugs in both groups were topical corticosteroid, antibiotic and cycloplegic drops. Periodic slitlamp examinations and photographic documentations were carried out to find any evidence of aftercataract. At the end ot 8 weeks, histopathological examination was carried out to document any evidence of aftercataract. <i>Result:</i> Overall, evidence of aftercataract was seen in 6 rabbits in the control group and 3 in the Catalin group; the degree of PCO was higher in the placebo group. <i>Conclusion:</i> We found that Catalin played some role in preventing PCO.
Cystine Transport Activity of Heterozygous rBAT Mutants Expressed in <i>Xenopus</i> Oocytes
Authors: Ishihara Masanari , Ogura Takehiko , Akakura Koichiro , Egoshi Ken-ichi , Mikami Kazuo , Nakaya Haruaki , Ito Haruo 
Published: April 2003

The rBAT gene encodes a transport protein for cystine and dibasic amino acids. It is a candidate gene for type I cystinuria, a genetic disorder inherited as an autosomal-recessive trait. Recently, several mutations in rBAT from Japanese patients with cystinuria have been reported from our laboratory. Some of these patients were heterozygous, which appears to be inconsistent with the previous concept that mutations in rBAT are recessive. To investigate the function of heterozygous mutants, we introduced these mutations into rBAT gene and analyzed the transport activity of cystine associated with the mutants in <i>Xenopus</i> oocytes. Co-injection of the mutant T1037C (L346P) and the polymorphism G1854A (M6181) into <i>Xenopus</i> oocytes produced a transport activity of 67.9% of the wild type. Oocytes co-injected with T2017C (C673R) and wild type had a transport activity of 70.3% of the wild type. These findings indicate that the heterozygous mutants show decreased transport activity compared to wild-type rBAT. Further, some mutants in rBAT may show decreased cystine transport activity even in heterozygous condition, which may contribute to stone-forming cystinuria.
Modified Technique of Gasless Laparoscopic Cholecystectomy in a Developing Country: A 5-Year Experience
Authors: Nande Anand G. , Shrikhande Shailesh V. , Rathod Vipulroy , Adyanthaya Kishor , Shrikhande Vinayak N. 
Published: April 2003

<i>Background:</i> Concerns and disadvantages associated with pneumoperitoneum have led surgeons to search for alternative techniques of exposure in laparoscopic surgery. We devised a modified technique of gasless laparoscopic cholecystectomy based on the concept of mechanical retraction of the abdominal wall. <i>Patients and Methods:</i> 337 males and 663 females, mean age 52 (7–87) years and mean weight 68 (28–126) kg, with gallstone disease and subjected to this technique were evaluated retrospectively (1992–1997). Towel clips were applied at 3 points on the abdominal wall and it was lifted without creating a pneumoperitoneum. A single surgical team specialized and experienced in biliary surgery performed all the surgeries. <i>Results:</i> Of 1,000, 46 patients weighing more than 85 kg required a combination of mechanical abdominal wall retraction and minimal pressure pneumoperitoneum (5 mm Hg). The conversion rate was 6% but none were related to limitations of the technique. Technique-related morbidity was minimal. No common bile duct or visceral injury was recorded and mortality was 0%. <i>Conclusion:</i> Gasless laparoscopic cholecystectomy is a feasible, safe and effective alternative to the pneumoperitoneum technique. It probably costs less and is therefore more useful in developing countries. However, it has limitation in overweight patients who are infrequently encountered in our population.
Temporal Constraints on Visually Directed C-Start Responses: Behavioral and Physiological Correlates
Authors: Canfield James G. 
Published: April 2003

To study the modulatory influences of visual information on Mauthner (M-) initiated C-start responses, short interval visual stimuli were presented to individual cichlid fish prior to being startled with a sound pulse. Because the axon of each Mauthner neuron activates trunk musculature contralateral to the soma, the initial direction of an ensuing startle response provides a behavioral measure of which cell has been driven closer to threshold by visual cues at the time the sound pulse causes one cell to fire. When an LED was illuminated on one side of the fish for 10 ms prior to a startling sound pulse, cichlids reliably turned toward the visual cue. At durations of 15 and 20 ms, fish turned away from the same stimulus. Thus, behavioral evidence suggests that the M-cell contralateral to a visual stimulus appears to be excited first but visual excitation of the M-cell ipsilateral to the visual stimulus follows and predominates. Consistent with the behavioral results, visually evoked excitatory potentials recorded intracellularly in the cichlid M-cells were complex, with initial PSPs showing latencies of about 11.6 ms from contralateral eye stimulation and 15.5 ms from stimulating the ipsilateral eye. PSP latencies in goldfish were longer and more similar for stimuli to the two eyes (about 22 ms). For contrast, sound-evoked PSPs begin within 2 ms. The relative long latencies for visually regulating M-cell function suggest that vision is most adaptive for biasing response direction prior to rather than during a predator’s attack.
Olive Oil and Red Wine Antioxidant Polyphenols Inhibit Endothelial Activation
Authors: Carluccio Maria Annunziata , Siculella Luisa , Ancora Maria Assunta , Massaro Marika , Scoditti Egeria , Storelli Carlo , Visioli Francesco , Distante Alessandro , De Caterina Raffaele 
Published: April 2003

Objective—Epidemiology suggests that Mediterranean diets are associated with reduced risk of cardiovascular disease. Because monocyte adhesion to the endothelium is crucial in early atherogenesis, we evaluated whether typical olive oil and red wine polyphenols affect endothelial–leukocyte adhesion molecule expression and monocyte adhesion.Methods and Results—Phytochemicals in olive oil and red wine, including oleuropein, hydroxytyrosol, tyrosol, elenolic acid, and resveratrol, with or without antioxidant activity, were incubated with human umbilical vein endothelial cells for 30 minutes, followed by co-incubation with bacterial lipopolysaccharide or cytokines to trigger adhesion molecule expression. At nutritionally relevant concentrations, only oleuropein, hydroxytyrosol, and resveratrol, possessing a marked antioxidant activity, reduced monocytoid cell adhesion to stimulated endothelium, as well as vascular cell adhesion molecule-1 (VCAM-1) mRNA and protein by Northern analysis and cell surface enzyme immunoassay. Reporter gene assays with deletional VCAM-1 promoter constructs indicated the relevance of nuclear factor-κB, activator protein-1, and possibly GATA binding sites in mediating VCAM-1 transcriptional inhibition. The involvement of nuclear factor-κB and activator protein-1 was finally demonstrated at electrophoretic mobility shift assays.Conclusions—Olive oil and red wine antioxidant polyphenols at nutritionally relevant concentrations transcriptionally inhibit endothelial adhesion molecule expression, thus partially explaining atheroprotection from Mediterranean diets.
Changes in Perlecan Expression During Vascular Injury
Authors: Kinsella Michael G. , Tran Phan-Kiet , Weiser-Evans Mary C.M. , Reidy Michael , Majack Richard A. , Wight Thomas N. 
Published: April 2003

Objective—Vascular smooth muscle cells (SMCs), activated by growth factors after arterial injury, migrate and proliferate to expand the intima of the blood vessel. During intimal expansion, proliferation is suppressed and an increasingly large proportion of the neointimal mass is composed of newly synthesized extracellular matrix (ECM). We sough to determine whether the ECM heparan sulfate proteoglycan (HSPG) perlecan, which inhibits SMC proliferation in vitro, also accumulates and limits SMC proliferation during neointimal expansion.Methods and Results—Perlecan expression and accumulation were analyzed by immunohistochemistry and in situ hybridization during neointima formation after balloon catheter injury to the rat carotid artery. Perlecan expression was low in uninjured vessels and up to 7 days after injury, during maximal SMC proliferation. By 14 days after injury, perlecan was dramatically increased, and immunostaining remained heavy throughout the advanced lesion, 35 to 42 days after injury. Finally, explants of intimal tissue from 35- to 42-day neointimal lesions were digested with glycosaminoglycanases to determine whether endogenous HSPGs inhibit intimal SMC proliferation. SMCs within HS-depleted, but not chondroitinase ABC–treated or mock-incubated, explants were found to proliferate in response to platelet-derived growth factor BB.Conclusions—HSPGs, such as perlecan, may inhibit the proliferative response of SMCs after vascular injury.
Intra-Arterial Tumor Necrosis Factor-α Impairs Endothelium-Dependent Vasodilatation and Stimulates Local Tissue Plasminogen Activator Release in Humans
Authors: Chia Stanley , Qadan Motaz , Newton Richard , Ludlam Christopher A. , Fox Keith A.A. , Newby David E. 
Published: April 2003

Objective—Inflammation contributes to the pathogenesis of cardiovascular disease, potentially through the actions of proinflammatory cytokines. We assessed the direct effects of local intra-arterial tumor necrosis factor-α (TNF-α), interleukin-6, and endotoxin on blood flow and endogenous tissue plasminogen activator (t-PA) release in vivo in humans.Methods and Results—In a double-blind, randomized, placebo-controlled trial, blood flow, plasma cytokine, and fibrinolytic parameters were measured using venous occlusion plethysmography and blood sampling. Ten subjects received intrabrachial TNF-α, interleukin-6, and endotoxin infusions, and 8 additional subjects received intrabrachial infusions of bradykinin, acetylcholine, and sodium nitroprusside after pretreatment with TNF-α. TNF-α but not interleukin-6, endotoxin, or placebo caused a gradual and sustained ≈20-fold increase in plasma t-PA concentrations (P<0.001) that was associated with elevated plasma interleukin-6 concentrations (P<0.05) but without an effect on blood flow or plasminogen activator inhibitor type 1 antigen. Compared with placebo, TNF-α pretreatment impaired bradykinin- and acetylcholine-induced vasodilatation (P<0.03) and resulted in a doubling of bradykinin-induced t-PA release (P<0.05).Conclusions—Intra-arterial TNF-α causes an acute local vascular inflammation that is associated with impaired endothelium-dependent vasomotion as well as a sustained and substantial increase in endothelial t-PA release. TNF-α has potentially both adverse vasomotor and beneficial profibrinolytic effects on endothelial function.
Inhibition of NF-κB essentially contributes to arsenic-induced apoptosis
Authors: Mathas Stephan , Lietz Andreas , Janz Martin , Hinz Michael , Jundt Franziska , Scheidereit Claus , Bommert Kurt , Dörken Bernd 
Published: April 2003

Abstract
Arsenic can induce apoptosis and is an efficient drug for the treatment of acute promyelocytic leukemia. Currently, clinical studies are investigating arsenic as a therapeutic agent for a variety of malignancies. In this study, Hodgkin/Reed-Sternberg (HRS) cell lines served as model systems to characterize the role of nuclear factor–κB (NF-κB) in arsenic-induced apoptosis. Arsenic rapidly down-regulated constitutive IκB kinase (IKK) as well as NF-κB activity and induced apoptosis in HRS cell lines containing functional IκB proteins. In these cell lines, apoptosis was blocked by inhibition of caspase-8 and caspase-3–like activity. Furthermore, arsenic treatment down-regulated NF-κB target genes, including tumor necrosis factor-αreceptor–associated factor 1 (TRAF1), c-IAP2, interleukin-13 (IL-13), and CCR7. In contrast, cell lines with mutated, functionally inactive IκB proteins or with a weak constitutive IKK/NF-κB activity showed no alteration of the NF-κB activity and were resistant to arsenic-induced apoptosis. A direct role of the NF-κB pathway in arsenic-induced apoptosis is shown by transient overexpression of NF-κB–p65 in L540Cy HRS cells, which protected the cells from arsenic-induced apoptosis. In addition, treatment of NOD/SCID mice with arsenic trioxide induced a dramatic reduction of xenotransplanted L540Cy Hodgkin tumors concomitant with NF-κB inhibition. We conclude that inhibition of NF-κB contributes to arsenic-induced apoptosis. Furthermore, pharmacologic inhibition of the IKK/NF-κB activity might be a powerful treatment option for Hodgkin lymphoma.
G-CSF as immune regulator in T cells expressing the G-CSF receptor: implications for transplantation and autoimmune diseases
Authors: Franzke Anke , Piao Wenji , Lauber Jörg , Gatzlaff Patricia , Könecke Christian , Hansen Wiebke , Schmitt-Thomsen Angela , Hertenstein Bernd , Buer Jan , Ganser Arnold 
Published: April 2003

AbstractResults from experimental models, in vitro studies, and clinical data indicate that granulocyte colony-stimulating factor (G-CSF) stimulation alters T-cell function and induces Th2 immune responses. The immune modulatory effect of G-CSF on T cells results in an unexpected low incidence of acute graft-versus-host disease in peripheral stem cell transplantation. However, the underlying mechanism for the reduced reactivity and/or alloreactivity of T cells upon G-CSF treatment is still unknown. In contrast to the general belief that G-CSF acts exclusively on T cells via monocytes and dendritic cells, our results clearly show the expression of the G-CSF receptor in class I– and II– restricted T cells at the single-cell level both in vivo and in vitro. Kinetic studies demonstrate the induction and functional activity of the G-CSF receptor in T cells upon G-CSF exposure. Expression profiling of T cells from G-CSF–treated stem cell donors allowed identification of several immune modulatory genes, which are regulated upon G-CSF administration in vivo (eg, LFA1-α, ISGF3-γ) and that are likely responsible for the reduced reactivity and/or alloreactivity. Most importantly, the induction of GATA-3, the master transcription factor for a Th2 immune response, could be demonstrated in T cells upon G-CSF treatment in vivo accompanied by an increase of spontaneous interleukin-4 secretion. Hence, G-CSF is a strong immune regulator of T cells and a promising therapeutic tool in acute graft-versus-host disease as well as in conditions associated with Th1/Th2 imbalance, such as bone marrow failure syndromes and autoimmune diseases.
Immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies inhibit megakaryocytopoiesis in vitro
Authors: Chang Mei , Nakagawa Peggy A. , Williams Shirley A. , Schwartz Michael R. , Imfeld Karen L. , Buzby Jeffrey S. , Nugent Diane J. 
Published: April 2003

Abstract
To determine if megakaryocytes are targeted by immune thrombocytopenic purpura (ITP) autoantibodies, as are platelets, we have studied the effects of ITP plasma on in vitro megakaryocytopoiesis. Umbilical cord blood mononuclear cells were incubated in the presence of thrombopoietin and 10% plasma from either ITP patients (n = 53) or healthy donors. The yield of megakaryocytic cells, as determined by flow cytometry, was significantly reduced in the presence of ITP plasma containing antiplatelet glycoprotein Ib (GPIb) autoantibodies (P &lt; .001) as compared with both the control and patient plasma with no detectable anti-GPIIb/IIIa or anti-GPIb autoantibodies. Platelet absorption of anti-GPIb autoantibodies in ITP plasmas resulted in double the megakaryocyte production of the same plasmas without absorption, whereas platelet absorption of control plasma had no effect on megakaryocyte yield. Furthermore, 2 human monoclonal autoantibodies isolated from ITP patients, 2E7, specific for human platelet glycoprotein IIb heavy chain, and 5E5, specific for a neoantigen on glycoprotein IIIa expressed on activated platelets, had significant inhibitory effects on in vitro megakaryocytopoiesis (P &lt; .001). Taken together, these data indicate that autoantibodies against either platelet GPIb or platelet GPIIb/IIIa in ITP plasma not only are involved in platelet destruction, but may also contribute to the inhibition of platelet production.
Human CD34+ hematopoietic stem cells capable of multilineage engrafting NOD/SCID mice express flt3: distinct flt3 and c-kit expression and response patterns on mouse and candidate human hematopoietic stem cells
Authors: Sitnicka Ewa , Buza-Vidas Natalija , Larsson Staffan , Nygren Jens M. , Liuba Karina , Jacobsen Sten Erik W. 
Published: April 2003

AbstractThe cytokine tyrosine kinase receptors c-kit and flt3 are expressed and function in early mouse and human hematopoiesis. Through its ability to promote ex vivo expansion and oncoretroviral transduction of primitive human hematopoietic progenitors, the flt3 ligand (FL) has emerged as a key stimulator of candidate human hematopoietic stem cells (HSCs). However, recent studies in the mouse suggest that though it is present on short-term repopulating cells, flt3 is not expressed on bone marrow long-term reconstituting HSCs, the ultimate target for the development of cell replacement and gene therapy. Herein we demonstrate that though only a fraction of human adult bone marrow and cord blood CD34+long-term culture-initiating cells (LTC-ICs) express flt3, most cord blood lymphomyeloid HSCs capable of in vivo reconstituting nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice are flt3+. The striking difference in flt3 and c-kit expression on mouse and candidate human HSCs translated into a corresponding difference in flt3 and c-kit function because FL was more efficient than SCF at supporting the survival of candidate human HSCs. In contrast, SCF is far superior to FL as a viability factor for mouse HSCs. Thus, the present data provide compelling evidence for a contrasting expression and response pattern of flt3 and c-kit on mouse and human HSCs.
Transient expansion of Mac1+Ly6-G+Ly6-C+ early myeloid cells with suppressor activity in spleens of murine radiation marrow chimeras: possible implications for the graft-versus-host and graft-versus-leukemia reactivity of donor lymphocyte infusions
Authors: Billiau An D. , Fevery Sabine , Rutgeerts Omer , Landuyt Willy , Waer Mark 
Published: April 2003

AbstractA murine model of minor histocompatibility antigen (miHCag)–mismatched bone marrow transplantation (BMT) was used to study the development of immunoregulatory cells in the posttransplantation period and their possible involvement in the dissociated graft-versus-host (GVH) and graft-versus-leukemia (GVL) reactivity of posttransplantation donor lymphocyte infusions (DLIs). DLI, applied immediately after BMT, induced GVH disease (GVHD), but when DLI was delayed for 3 weeks, GVHD was avoided while a distinct GVL response was allowed to develop. A population of Mac1+Ly6-G+Ly6-C+ immature myeloid cells, found in small numbers in normal mice, strongly expanded in spleens of chimeras, reaching a maximum level at week 3 and returning to base level by week 12. Upon isolation, these cells exhibited interferon-γ (IFN-γ)–dependent, nitric oxide (NO)–mediated suppressor activity toward in vitro alloresponses, suggesting that, after in vivo DLI, they are activated by IFN-γ to produce NO and suppress GVH reactivity. Because not only alloactivated T-cell proliferation but also leukemia cell growth was found susceptible to inhibition by exogenous NO, in vivo activation of these cells after DLI may explain the occurrence of a GVL effect despite suppression of GVHD. This suggested sequence of events was supported by the finding that the ex vivo antihost proliferative response of spleen cells, recovered shortly after in vivo DLI, was characterized by strong mRNA production of the monokines interleukin-1 (IL-1), IL-6, and tumor necrosis factor-α (TNF-α) and of inducible nitric oxide synthase (iNOS). Our data suggest that transiently expanding Mac1+Ly6-G+Ly6-C+ immature myeloid cells (probably as a result of extramedullary myelopoiesis) may play a role in controlling GVH while promoting GVL reactivity of DLI after allogeneic BMT.