bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving Influence of Insulin on Cognitive Functions in Humans
Authors: Kern Werner , Peters Achim , Fruehwald-Schultes Bernd , Deininger Eva , Born Jan , Fehm Horst L. 
Published: April 2003

Insulin receptors have been identified in limbic brain structures, but their functional relevance is still unclear. In order to characterize some of their effects, we evaluated auditory evoked brain potentials (AEP) in a vigilance task, behavioral measures of memory (recall of words) and selective attention (Stroop test) during infusion of insulin. The hormone was infused at two different rates (1.5 mU/kg × min, ‘low insulin’, and 15 mU/kg × min, ‘high insulin’), inducing respectively serum levels of 543 ± 34 and 24,029 ± 1,595 pmol/l. This experimental design allowed to compare cognitive parameters under two conditions presenting markedly different insulin levels, but with minimal incidence on blood glucose concentrations since these were kept constant by glucose infusion. A ‘no insulin treatment’ group was not included in order to avoid leaving patients infused with glucose without insulin treatment. Measures were taken during a baseline phase preceding insulin infusion and every 90 min during the 360 min of insulin infusion. Compared with ‘low insulin’, ‘high insulin’ induced a slow negative potential shift in the AEP over the frontal cortex (average amplitude, high insulin: 0.27 ± 0.48 µV; low insulin: 1.87 ± 0.48 µV, p < 0.005), which was paralleled by enhanced memory performance (words recalled, high insulin: 22.04 ± 0.93; low insulin: 19.29 ± 0.92, p < 0.05). Also, during ‘high insulin’ subjects displayed enhanced performance on the Stroop test (p < 0.05) and expressed less difficulty in thinking than during ‘low insulin’ (p < 0.03). Results indicate an improving effect of insulin on cognitive function, and may provide a frame for further investigations of neurobehavioral effects of insulin in patients with lowered or enhanced brain insulin, i.e., patients with Alzheimer’s disease or diabetes mellitus.
Association between GABA-A Receptor Alpha 5 Subunit Gene Locus and Schizophrenia of a Later Age of Onset
Authors: Papadimitriou George , Dikeos Dimitris , Daskalopoulou Eugenia , Karadima Georgia , Avramopoulos Dimitrios , Contis Costas , Stefanis Costas 
Published: April 2003

Heritability is considered to be a major etiologic factor for schizophrenia. Among the genes considered as candidates for the disease, are those related to GABAergic neurotransmission. Our aim was to test for a genetic association between GABA-A receptor alpha 5 subunit gene locus (GABRA<sub>5</sub>) and schizophrenia. Genotyping of the GABRA<sub>5</sub> locus was performed by the use of a dinucleotide (CA) repeat marker in 46 schizophrenic patients and 50 healthy individuals, all unrelated Greeks. Eight alleles were identified, 276–290 bp long. A nonsignificant excess of the 282-bp allele, which was found in a previous study in a Greek population to be associated with bipolar affective disorder, was observed in schizophrenic patients (33.8 vs. 23.9% in the controls). The frequency of this allele was 43.3% among patients with a later age of onset (over 25 years), differing at a statistically significant level from the controls (p < 0.05). These results suggest that common pathophysiological mechanisms may possibly underlie affective disorders and schizophrenia, at least in a subgroup of patients.
Treatment of Advanced Stage Hodgkin’s Disease
Authors: Tesch H. , Sieber M. , Diehl V. 
Published: April 2003

Hodgkin’s disease remains one of the few malignant diseases which can be cured by modern chemotherapy in most cases even in advanced stages. Adriamycin-containing chemotherapy regimens are considered as the standard therapy which induce long-term remission in about 60–70% of patients. The ABVD scheme, developed by Bonadonna and colleagues in Milan, has a favorable toxicity profile and causes less myelotoxicity, acute leukemia or sterility relative to many previous treatment programs containing alkylating agents. However, 20– 30 % of patients eventually relapse and are then frequently treated with high-dose programs including stem cell transplantation. There are two major goals in advanced Hodgkin’s disease: (1) to improve the cure rate and (2) to reduce acute and long-term toxicities. The recent definition of prognostic factors identified patients who are at a high risk of treatment failure as well as those in whom less toxic approaches can be applied. The optimal approach or program has not yet been defined, although new chemotherapy regimens such as BEACOPP and Stanford V with increased tumor response rates have been identified. These new drug combinations are currently analyzed and compared with ABVD in several international trials. While the addition of radiotherapy improved disease control in some trials a survival benefit was not identified and the role of radiotherapy remains controversial. High dose programs remain experimental in advanced stage Hodgkin’s disease and should be restricted to prospective clinical trials.
Overexpression of Vascular Endothelial Growth Factor C Is Related to Lymphogenous Metastasis in Early Gastric Carcinoma
Authors: Kabashima Akira , Maehara Yoshihiko , Kakeji Yoshihiro , Sugimachi Keizo 
Published: April 2003

Vascular endothelial growth factor C (VEGF-C) is considered to be potentially lymphangiogenic and can selectively induce hyperplasia of the lymphatic vasculature. In this study, we clarified the clinicopathological features of early gastric carcinoma (EGC) that has metastasized to the lymph nodes, as well as the correlation between lymphogenous metastases in EGC and the expression of VEGF-C and VEGF. We selected 35 cases of lymph node metastasis-positive [n(+)] EGC and 70 cases of lymph node metastasis-negative [n(–)] EGC for the present study. The expression of VEGF and VEGF-C was investigated with immunohistochemical staining using monoclonal antibodies against VEGF and VEGF-C. Clinicopathologically, there were significant differences in median size (4.1 ± 2.4 vs. 2.4 ± 1.7 cm), lymphatic invasion (54 vs. 4%) and venous invasion (23 vs. 3%) between n(+) EGC and n(–) EGC. Immunohistochemically, the incidence of positive expression of VEGF-C in lymphatic invasion-positive EGC (36%) was significantly higher than that in lymphatic invasion-negative EGC (14%). The incidence of positive expression of VEGF-C in n(+) or venous invasion-positive EGC tended to be higher than that in n(–) or venous invasion-negative EGC. In conclusion, lymphatic invasion was significantly increased in VEGF-C-positive EGC.
Investigation of the ‘Fines’ Hypothesis of Primary Open-Angle Glaucoma: The Possible Role of Alpha-Crystallin
Authors: Doss Ellen W. , Ward K.A. , Koretz J.F. 
Published: April 2003

Primary open-angle glaucoma is a disease caused by an increase in intraocular pressure due to a decreased facility of outflow of aqueous humor through the trabecular meshwork. The etiology of primary open-angle glaucoma is currently unknown, but it has been suggested that one possible mechanism may be the obstruction of flow through the trabecular meshwork by small macromolecules, analogous to the effect of ‘fines’ in column chromatography. One such candidate is α-crystallin, a lens protein which may be released into the aqueous humor from lens fiber cells at concentrations below that necessary for the formation of the native aggregate. Results of in vitro binding experiments indicate that α-crystallin and serum albumin, which is secreted at the anterior root of the iris and is believed to act as a protein escort through the trabecular meshwork in mammalian eyes, will interact at concentrations of α-crystallin up to the critical micelle concentration for α-crystallin (3.5–5 mg/ml, or 0.18–0.25 m<i>M</i>). There is little interaction at or above this concentration. This binding could serve the necessary function of preventing interactions between α-crystallin monomers or small aggregates and hydrophobic surfaces within the trabecular meshwork. Since, however, the interaction between the two proteins is not extremely strong, the accumulation of unbound α-crystallin monomers and/or dimers could contribute to the development of primary open-angle glaucoma.
TGF Beta Secretion Modulates the Density-Dependent Growth of Pig Retinal Pigment Epithelium in vitro
Authors: Tezel Tongalp H. , Del Priore Lucian V. 
Published: April 2003

<i>Background:</i> We aimed to identify the cytokine(s) responsible for the density-dependent growth regulation of pig retinal pigment epithelium (RPE) in vitro. <i>Methods:</i> Confluent monolayers of primary pig RPE were established on bovine corneal endothelial extracellular matrix-coated tissue culture well inserts wrapped with dialysis membranes with different molecular weight cutoffs (0.5–50 kDa). These confluent RPE monolayers were then cocultured with first passage porcine RPE plated at a density of 1 cell/mm<sup>2</sup>, so that the newly plated RPE was bathed with different molecular weight fractions of the confluent cell media. Growth rates of the newly plated RPE were determined 72 h after plating and the molecular weight fraction of the confluent cell medium that inhibits the RPE proliferation was determined. First passage pig RPE (1 cell/mm<sup>2</sup>) were cocultured with confluent monolayers of primary pig RPE on inserts in the presence of different amounts of TGF-β neutralizing antibody (0.1–100 µg/ml). Growth rates of the newly plated RPE were calculated 72 h after plating to determine the antibody concentration that would maximize the growth rate of the newly plated RPE in the presence of an adjacent confluent RPE monolayer. <i>Results:</i> The growth rate of the newly plated RPE decreased when RPE were bathed with the 10- to 25-kDa fractions of medium from an adjacent confluent RPE monolayer. This growth inhibition reached statistical significance with the 25- to 50-kDa fractions (p < 0.05), and was abolished by adding pan-specific neutralizing antibody against TGF-β (0.1–5 µg/ml). Blocking greater amounts of TGF-β in the medium with higher doses of antibody (>10 µg/ml) also inhibited the growth of the newly plated RPE, in the presence or absence of a neighboring confluent cell layer. <i>Conclusion:</i> The TGF-β family of cytokines mediates the density-dependent growth suppression of RPE in vitro. Neutralizing the effect of these cytokines by adding anti-TGF-β antibodies can result in more rapid growth of the RPE in vivo.
Epidemiological Study of Nontraumatic Phakic Rhegmatogenous Retinal Detachment
Authors: Ivanišević Milan , Bojić Lovro , Eterović Davor 
Published: April 2003

We studied the epidemiological characteristics of nontraumatic phakic rhegmatogenous retinal detachment (RRD) in a defined population of Split-Dalmatia County, Croatia. A total of 278 eyes of 272 patients developed RRD during an 11-year period, 1988–1998, with a population of 465,947. The annual incidence was 5.4 per 100,000 population. The mean age of patients was 58.3 years, and the sex distribution corresponded with that in the general population. There was insignificant preponderance of right eye involvement. Bilaterality was observed in 2.2%. The presence of myopia was diagnosed in 46.9% eyes.
Retinal Cells Produce TIMP-1 and TIMP-2 in Response to Cyclic Mechanical Stretching
Authors: Namba Masako , Matsuo Toshihiko , Shiraga Fumio , Ohtsuki Hiroshi 
Published: April 2003

<i>Purpose:</i> Tissue inhibitors of metalloproteinases (TIMPs) are crucial for the maintenance of retinal extracellular matrix such as interphotoreceptor matrix and internal limiting membrane. This study is to examine whether retinal cells respond to mechanical stretching and produce TIMPs. <i>Methods: </i>Chick retinal adherent cells in near confluency were exposed to mechanical stretching of the bottom of a 6-cm Petri dish at the maximum magnitude of 4,500 microstrain and at a cycle of 30 s for 72 h. TIMP-1 and TIMP-2 levels in the medium at 24, 48 and 72 h after the beginning of stretching were measured by enzyme immunoassay, and their expression was examined by immunohistochemistry. <i>Results:</i> The number of retinal cells during the 72-hour period of stretching did not change significantly both in the stretched group and in the nonstretched control group. Retinal cells in the stretched group produced significantly larger amounts of TIMP-1 and TIMP-2 at 48 h after stretching, compared with nonstretched controls (p = 0.0163 and p = 0.047, respectively, Mann-Whitney U test). Immunohistochemically, a large part of retinal cells in nonstretched Petri dishes was positive for glial fibrillary acidic protein, indicative of glial cells, while some small foci of cells were positive for neuron-specific enolase, indicative of neurons. Fluorescent double labeling demonstrated that both glial cells and neurons were positive for TIMP-1 and TIMP-2. <i>Conclusion:</i> Chick retinal cells, most of which were glial cells mixed with a small number of neurons, produced TIMP-1 and TIMP-2. Their production was enhanced by cyclic mechanical stretching.
Allopurinol Attenuates Endolymphatic Hydrops in the Guinea Pig Cochlea
Authors: Shinomori Yusuke , Kimura Robert S. 
Published: April 2003

Based on the hypothesis that Ca<sup>2+</sup> overload in the scala media may produce endolymphatic hydrops and generate free oxygen radicals (FOR), allopurinol, a xanthine oxidase inhibitor and free radical scavenger, was administered to guinea pigs after the surgical obliteration of the endolymphatic duct. Allopurinol was given intraperitoneally (50 mg/kg/day) for 15 days starting 1 day prior to the surgical blockage procedure. Measurements from histological serial sections of these temporal bones showed that the total volume of the scala media was significantly reduced (p = 0.007) compared with control hydropic ears. There was an indication of reduced incidence of atrophy in sensorineural structures and stria vascularis. These findings suggest that allopurinol may attenuate the development of endolymphatic hydrops and cell damage by preventing the formation of FOR or scavenging FOR. This study may lead to a new aspect of treatment for Menière’s disease.
Interleukin-1β Induces Different Gene Expression of Stromelysin, Aggrecan and Tumor-Necrosis-Factor-Stimulated Gene 6 in Human Osteoarthritic Chondrocytes in vitro
Authors: Stöve Johannes , Huch Klaus , Günther Klaus-Peter , Scharf Hanns-Peter 
Published: April 2003

<i>Objective:</i> To analyze the gene expression of osteoarthritic chondrocytes cultured in alginate after stimulation with interleukin (IL)-1β. <i>Methods:</i> Chondrocytes were isolated from osteoarthritic cartilage obtained during total knee replacement by sequential enzymatic digestion. After suspension in alginate, cells were cultured with and without 100 pg/ml IL-1β. Quantitative RT-PCR reaction was used to estimate the messenger RNA (mRNA) of three different metabolites [tumor-necrosis-factor-stimulated gene 6 (TSG-6), stromelysin-1 (MMP-3) and aggrecan (AGG)]. <i>Results: </i> After having shown the precision of quantitative PCR, this method allowed us to detect IL-1β-induced changes in mRNA of TSG-6, MMP-3 and AGG. MMP-3 was found to be the most abundant transcript, IL-1β induced a 12-fold upregulation of MMP-3 levels compared to control, and 7-fold of TSG-6. The AGG transcript level, indicating anabolic events, was found to be downregulated by between 2- and 3-fold. <i>Conclusions:</i> In our culture system, the response of osteoarthritic chondrocytes to IL-1β is preserved. Therefore, this system might be helpful for further investigation of the influences of drugs, cytokines and growth factors, for example, on the metabolism of chondrocytes at the level of gene transcription as the most basic level of regulation.
Ontogeny of Pig Discrete Peyer’s Patches: Distribution and Morphometric Analysis
Authors: Makala L.H.C. , Kamada T. , Nishikawa Y. , Nagasawa H. , Igarashi I. , Fujisaki K. , Suzuki N. , Mikami T. , Haverson K. , Bailey M. , Stokes C.R. , Bland P.W. 
Published: April 2003

We investigated the development of lymphoid and non-lymphoid cells in discrete Peyer’s patches (PP) of the pig using immuno-histology and image analysis. In newborn piglets discrete PP were mainly populated by CD2+, CD3+ T cells, and major histocompatibility complex class II+ cells, many of which were of macrophage and dendritic cell lineage. Four days after birth, cells were localized in defined regions: the follicle; the inter-follicular area and the dome region. Compartmentalization within the follicle started about 6 days after birth. The first signs of secondary follicles were seen from about 14 days. The pig discrete PP attained their mature structure at about 3 weeks after birth. Here we show that despite the demonstration at birth of the cell types that support antigen processing and presentation, PP did not fully differentiate morphologically until at least this time when antigen can be handled in an efficient manner.
Intraventricular Pressure Dynamics in Ventriculocholecystic Shunting: A Telemetric Study
Authors: Frim David M. , Lathrop Dawn , Chwals Walter J. 
Published: April 2003

Extracranial cerebrospinal fluid shunting is the current mainstay of therapy for hydrocephalus. The generally preferred extracranial site for cerebrospinal fluid absorption is the peritoneal space; however, the cardiac atrium and the pleura are also commonly used. On occasion other CSF recipient sites, such as the gallbladder, are used secondarily when the more common absorptive spaces are unavailable or unsuitable. The gallbladder, though, exhibits its own pressure dynamics in response to physiological stimuli. The effects of gallbladder contraction on intraventricular pressure (IVP) in the presence of a ventriculocholecystic (VGB) shunt are unknown. We had the opportunity to place a VGB shunt in a 4-year-old child who was coupled to a noninvasive telemonitor. After a period of acclimation, we examined the IVP dynamics of that shunting system both pre- and postprandially. We found that before ingestion of food, the gallbladder provides a CSF recipient site similar to that of the peritoneal space. However, after ingestion of a meal containing fat, we found that IVP rose more than 10 cm water in a stereotypic fashion consistent with postprandial gallbladder contraction. The increase in IVP lasted for several hours reaching a peak at approximately 75 min postprandially. We conclude that the VGB shunt is a viable alternative for extracranial cerebrospinal fluid shunting; however, one must be aware of the peculiar dynamics of this shunt in relation to food ingestion and the potential for unusually high IVPs.
Reinforcing Effects of MDMA (‘Ecstasy’) in Drug-Naive and Cocaine-Trained Rats
Authors: Ratzenboeck Elisabeth , Saria Alois , Kriechbaum Norbert , Zernig Gerald 
Published: April 2003

3,4-Methylenedioxymethamphetamine (MDMA; ‘ecstasy’) is one of the most prevalent illegal drugs of abuse among European adolescents, a population not generally experienced with respect to ‘hard’ drugs such as cocaine. We, therefore, determined the reinforcing effect of intravenously self-administered MDMA in a fixed ratio 1 time-out 150 s schedule of reinforcement in rats that were truly drug naive and compared it to cocaine-trained rats. The reinforcing effect of MDMA [0.032–10 mg/(kg·injection)] did not differ between drug-naive rats and cocaine-trained ones. MDMA sensitized the animals to its own rate-increasing effect but not to that of cocaine. When MDMA was tested after cocaine, there was no carryover of cocaine’s reinforcing effect to that of MDMA, suggesting that MDMA and cocaine produce distinct interoceptive stimuli in rats.
Acute Antidepressant-Like and Antianxiety-Like Effects of Tryptophan in Mice
Authors: Wong P.T.-H. , Ong Y.P. 
Published: April 2003

The antidepressant-like, antianxiety-like and sedative effects of tryptophan (TRP), in the absence and presence of <i>p</i>-chlorophenylalanine (<i>p</i>-CPA), and melatonin were studied in mice using the forced-swimming test, open-field test and activity cage, respectively. Single-dose TRP caused an antidepressant-like effect dose dependently up to 125 mg/kg. No significant effect was observed, however, when the TRP dose was increased to 250 mg/kg, i.e. a reversal of effect occurred at high dose. With <i>p</i>-CPA pretreatment, the effects observed at 125 and 250 mg/kg TRP were similar to those obtained at 50 and 125 mg/kg without <i>p</i>-CPA pretreatment, respectively. Melatonin also caused an antidepressant-like effect in a similar manner, but appeared to be less potent than TRP. These results strongly indicate that the antidepressant-like effect of TRP was due to its conversion to 5-hydroxytryptamine (5-HT). An antianxiety-like effect was observed for TRP only at 250 mg/kg dose together with <i>p</i>-CPA pretreatment, while no sedative effect was observed at all. In contrast, melatonin did not produce any antianxiety-like effect, but produced sedation at 200 mg/kg dose. It may be concluded that the antianxiety-like effect of TRP is unrelated to 5-HT and melatonin formation, but associated with TRP itself or, perhaps, with other anxiolytic metabolites.
Dual Effect of the Antianginal Drug Fendiline on Bladder Female Transitional Carcinoma Cells: Mobilization of Intracellular Ca<sup>2+</sup> and Induction of Cell Death
Authors: Jan Chung-Ren , Yu Chia-Cheng , Huang Jong-Khing 
Published: April 2003

The effect of fendiline, an antianginal drug, on cytosolic free Ca<sup>2+</sup> levels ([Ca<sup>2+</sup>]<sub>i</sub>) in populations of bladder female transitional carcinoma (BFTC) cells was explored using fura-2 as a Ca<sup>2+</sup> indicator. Fendiline at concentrations between 3 and 200 µmol/l increased [Ca<sup>2+</sup>]<sub>i</sub> in a concentration-dependent manner and the signal saturated at 100 µmol/l. The [Ca<sup>2+</sup>]<sub>i</sub> signal was biphasic, with an initial rise and a slow decay. Ca<sup>2+</sup> removal inhibited the Ca<sup>2+</sup> signal by about half in peak amplitude. Adding 3 mmol/l Ca<sup>2+</sup> increased [Ca<sup>2+</sup>]<sub>i</sub> in cells pretreated with 100 µmol/l fendiline in Ca<sup>2+</sup>-free medium, suggesting that fendiline induced Ca<sup>2+</sup> influx via capacitative Ca<sup>2+</sup> entry. In Ca<sup>2+</sup>-free medium, pretreatment with 1 µmol/l thapsigargin (an endoplasmic reticulum Ca<sup>2+</sup> pump inhibitor) to deplete the endoplasmic reticulum Ca<sup>2+</sup> store inhibited most of the 100 µmol/l fendiline-induced internal Ca<sup>2+</sup> release; and conversely, pretreatment with 100 µmol/l fendiline partly inhibited 1 µmol/l thapsigargin-induced Ca<sup>2+</sup> release. This indicates that the major internal Ca<sup>2+</sup> store of fendiline-induced [Ca<sup>2+</sup>]<sub>i</sub> increases is located in the endoplasmic reticulum. The Ca<sup>2+</sup> release induced by 100 µmol/l fendiline may be partly mediated by inositol 1,4,5-trisphosphate, because the [Ca<sup>2+</sup>]<sub>i</sub> increase was inhibited by 50% by inhibiting phospholipase C with 2 µmol/l U73122. Fendiline (100 µmol/l) decreased cell viability by 12–44% after being added to cells for 2– 30 min. Together, the findings indicate that in BFTC cells, fendiline exerts a dual effect: mobilization of intracellular Ca<sup>2+</sup> and induction of cell death.