bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Psoriatic Skin in Organ Culture: Comparison with Normal Skin Exposed to Exogenous Growth Factors and Effects of an Antibody to the EGF Receptor
Authors: Varani James , Kang Sewon , Stoll Stefan , Elder James T. 
Published: April 2003

Organ cultures were established from psoriatic lesional skin of 24 different individuals and maintained for 8 days under serum-free, growth-factor-free conditions. Nonlesional skin from 14 of the same individuals and normal skin from another 12 individuals were also maintained in organ culture. At the end of the incubation period, the tissues were fixed in formalin and examined histologically. Lesional skin continued to express features of psoriatic plaque, which included irregularly shaped epithelial cells arranged in a disorganized fashion, and elongation of the rete ridges with a thickening in their lower portion. Abnormal epidermal differentiation and separation of the upper epidermal layers from the lower layers was also a consistent feature. In contrast, nonlesional skin from psoriatic patients exhibited a histological appearance which resembled that of site-matched normal skin. When normal skin was exposed to a growth-factor-enriched culture medium during the 8-day incubation period, it exhibited a histological appearance similar to that of psoriatic skin. In addition to abnormal histological features, the psoriatic skin in organ culture released higher amounts of matrix metalloproteinase-9 (MMP-9; 92-kD gelatinase B/type IV collagenase) into the culture fluid than either nonlesional skin or normal skin. Organ cultures of psoriatic lesional skin from 6 individuals were maintained for 8 days in the presence of an antibody to the human epidermal growth-factor (EGF) receptor. The abnormal histological features of the psoriatic tissue were partially ameliorated in the presence of the antibody. These data suggest that growth factors which act through the EGF receptor help to maintain the psoriatic phenotype in organ culture. They also suggest that organ culture may provide a useful tool with which to elucidate the pathophysiological mechanisms of altered keratinocyte proliferation and differentiation in psoriasis.
Loss of Heterozygosity on the Short Arm of Chromosome 3 in Cervical Intra-Epithelial Neoplasia without Concomitant Cervical Carcinoma
Authors: Fouret Pierre J. , Dabit Dominique , Mergui Jean-Luc , Uzan Serge 
Published: April 2003

Losses of heterozygosity on the short arm of chromosome 3p are common in cervical carcinomas in the 3p13-3p21 region, and can be observed in intra-epipthelial lesions accompanying cervical cancers. As a preliminary attempt to determine whether these losses can be observed in intra-epithelial cervical lesions without concomitant invasive carcinoma, we have used two microsatellite markers located at the two most frequently deleted segments of the 3p13-3p21 region. We have studied 36 cases of grade II and grade III cervical intra-epithelial neoplasias obtained by conisation biopsies and 30 cases of cervical carcinoma including 3 micro-invasive squamous cell carcinomas. We found loss of heterozygosity or microsatellite instability in 6 of 16 (38%) and 9 of 23 (39%) informative cases of cervical carcinoma at 3p13 and 3p21, respectively. Four of 27 (15%) cases of cervical intra-epithelial neoplasia showed loss of heterozygosity at 3p13, whereas loss of heterozygosity or microsatellite instability at 3p21 was found in 5 of 19 cases (26%). No relationship was found between 3p loss of heterozygosity and human papillomavirus infection. In conclusion, losses of heterozygosity at 3p13 and 3p21 occur in premalignant lesions without concomitant invasive lesions. The prevalence and precise extent of these losses should be established by a more extensive analysis.
T Cells Mediate Treatment of Six-Day-Old Cytokine-Gene-Transfected Mouse Mammary Tumor
Authors: Matory Yvedt L. , Dorfman David M. , Chen Man , Wu Lei , Spanjaard Remco A. , Goedegebuure Peter S. , Eberlein Timothy J. 
Published: April 2003

We have previously shown that immunologically different mouse mammary cancer cell lines induce antitumor responses after IL2 or IL4 gene transfection. We now report the ability of cytokine-transfected tumors to induce eradication of established wild-type tumor. Animals with 6-day-old tumor treated with IL2-transfected cells also had significantly smaller tumors 2.8 and 1.7 cm<sup>2</sup> (EMT6 and 410.4). Findings were similar for IL4-transfected cells. Tumor infiltrating lymphocytes or cells from draining lymph nodes demonstrated tumor-specific in vitro cytotoxicity. Immunohistochemical studies revealed T cell infiltrates in transfected tumors.
Role of Laminin Isoforms in Glomerular Structure
Authors: Hansen Kim , Abrass ChristineK. 
Published: April 2003

Laminin along with collagen type IV, proteoglycans, and entactin are major components of basement membranes. Basement membrane components are synthesized at high levels during development. The formation of specialized basement membranes may play important roles in cell and tissue function by influencing cell proliferation, phenotype, migration and gene expression as well as tissue architecture. The growing diversity of laminin isoforms influences the formation of distinct basement membranes. Many of the laminin chains sequenced to date are expressed during glomerular development under strict temporal control. Also, some studies suggest that additional laminin chains exist and contribute to unique isoforms expressed within the renal glomerulus. This article will review the status of characterization of laminin isoforms expressed by glomerular cells, point out possible differences in isoforms expressed by different species, and discuss the implications of the complexity of glomerular laminins. In order to fully understand the nature of the glomerular laminins and their importance, information from studies of cells in culture, whole tissue, and those that use molecular and protein analysis must be integrated.
Differential Effects of Necrotic or Apoptotic Cell Uptake on Antigen Presentation by Macrophages
Authors: Barker Robert N. , Erwig Lars-Peter , Pearce Wayne P. , Devine Anne , Rees Andrew J. 
Published: April 2003

The induction of pathogenic immune responses may be dependent on the immune system receiving ‘danger’ signals resulting from tissue damage, rather than tolerogenic stimuli associated with normal cell turnover. The aim was to test this hypothesis by comparing the effects of the uptake of necrotic and apoptotic cells on the ability of antigen-presenting cells (APC) to stimulate immune responses in vitro. The experiments focused on presentation by the macrophage, which is the main cell type adapted for clearing cellular debris in vivo. Murine bone marrow-derived macrophages were pulsed with neutrophils that had been rendered apoptotic or necrotic, and tested for the ability to induce T cell responses. The macrophages that had taken up necrotic, but not apoptotic, cells were able to stimulate recall proliferation by ovalbumin-specific T cells. Furthermore, the response to the mitogen concanavalin A (Con A) was more than 6 times higher when macrophages had been pulsed with necrotic, in comparison with apoptotic, cells. In control experiments, macrophages that had not been exposed to dying neutrophils stimulated weak responses to ovalbumin and Con A. To determine why the uptake of apoptotic and necrotic cells exert opposing effects on the ability of macrophages to stimulate T cells, the expression of costimulatory molecules by treated macrophages, and their production of potentially immunomodulatory cytokines were measured. Flow cytometry revealed that macrophages that had taken up necrotic, but not apoptotic, neutrophils expressed increased levels of CD40 compared to untreated controls within 4 h. Macrophages pulsed with apoptotic cells secreted higher levels of transforming growth factor-β1 than those ingesting necrotic cells or untreated controls. Our interpretation of these results is that macrophages that have taken up necrotic cell debris present antigens to T lymphocytes with greater efficiency due to transient CD40 upregulation, whereas those that have ingested apoptotic cells are ineffective APC since they secrete inhibitory cytokine.
Effects of a High-Cholesterol Diet on Vascular and Endothelial Function in Rat Aorta
Authors: O’Rourke Mary , Docherty J.R. 
Published: April 2003

We have examined the effects of high cholesterol (1%) or normal diet for 8 weeks on vascular and endothelial responsiveness of rat aorta. The cholesterol diet produced a small but significant elevation of plasma cholesterol levels (vehicle: 0.95±0.13 mmol/l, n = 11; cholesterol fed: 1.40 ± 0.12 mmol/l, n = 14; p < 0.05). There were significant differences between control and high cholesterol groups in the contractile response to noradrenaline in rat aortic rings, both in terms of maximum response and potency. Both the potency of noradrenaline (NA) (pD<sub>2</sub> values; vehicle diet: 7.84 ± 0.08; cholesterol diet: 8.27 ± 0.09; p < 0.01) and the maximum response (vehicle diet: 0.78 ± 0.05 g; cholesterol diet: 0.95 ± 0.06 g; p < 0.05) were significantly greater in the high-cholesterol group. There were no significant differences between control and high cholesterol groups in endothelium-independent relaxations to sodium nitroprusside (SNP). When responses were correlated with plasma cholesterol levels, there was a significant negative correlation with maximum endothelium-dependent relaxation to ACh (r = 0.53, n = 16, p < 0.05), so that the maximum relaxation decreased with increasing plasma levels of cholesterol. There were no significant correlations between cholesterol levels and endothelium-independent relaxation to SNP or between cholesterol levels and vascular contractions to NA. In conclusion, cholesterol-fed normal Wistar rats show functional changes in vascular responsiveness even with a relatively small elevation of plasma cholesterol levels.
Effects of Chronic Central Infusion of Oxytocin on the Response of the Magnocellular Neuroendocrine System to Osmotic Stimulation
Authors: Koehler-Stec Ellen M. , Byers Amy , Summy-Long Joan Y. 
Published: April 2003

The effect of continuous intracerebroventricular (i.c.v.) infusion of oxytocin (OT) on the release of OT and vasopressin (VP) following osmotic stimulation was studied in ovariectomized rats treated peripherally with gonadal steroids to simulate late gestation/lactation. Artificial cerebrospinal fluid (CSF) with or without OT (2 ng/µg) was infused (0.5 µl/h) i.c.v. continuously for 7 days along with sequential peripheral administration of progesterone (2 mg/kg i.m.) for 4 days, then 17-β-estradiol (200 µg/kg i.m.) for 2 days. Following 7 days of OT infusion, isotonic (0.15 mol/l NaCl) or hypertonic (1.5 mol/l NaCl) saline was injected (15 ml/kg s.c.); the animals were decapitated 1 h later. Animals infused centrally with OT had higher basal levels of OT in plasma (p < 0.01 vs. CSF). While osmotic stimulation increased plasma levels of both OT and VP (0.15 mol/l NaCl < 1.5 mol/l NaCl; p < 0.01), only circulating VP was enhanced further (p < 0.01) in animals infused with OT compared with those receiving CSF. These changes in hormone levels could not be explained by differences in neural lobe stores of OT or VP or by alterations in daily water intake during the infusion period. Thus, chronic i.c.v. infusion of OT stimulates basal release of OT and increases the response of the VP system to osmotic stimulation.
Angiotensin-Converting Enzyme Inhibition Attenuates Proteinuria and Renal TGF-β1 mRNA Expression in Rats with Chronic Renal Disease
Authors: Ali Shujath M. , Laping Nicholas J. , Fredrickson Todd A. , Contino Lisa C. , Olson Barbara A. , Anderson Karen , Brooks David P. 
Published: April 2003

Evidence suggests that transforming growth factor beta 1 (TGF-β1), a multifunctional cytokine, induces renal extracellular matrix production and glomerular hypertrophy. The aim of the present study was to investigate the effect of captopril on the expression of TGF-β1 mRNA in a rat model of chronic renal failure: five-sixths nephrectomy. Chronic renal disease was induced by removal of the right kidney and ligation of three blood vessels supplying the left kidney. Sham-operated animals were used as controls. RNA was extracted from the viable remnant kidney of rats 1 day and 1 and 2 weeks following five-sixths nephrectomy and from the kidneys of rats who underwent sham sugery. TGF-β1 mRNA was induced within 24 h of partial nephrectomy, similar to that reported for early-onset genes. Subsequently, TGF-β1 mRNA expression continued to increase over the next 2–4 weeks. The upregulation of TGF-β1 correlated with the degree of proteinuria. Both the increase in TGF-β1 mRNA and proteinuria were abrogated by captopril treatment. In addition, no change in expression of ALK-5 or type II TGF-β receptors following five-sixths nephrectomy was observed. These data suggest that captopril may protect against development of glomerulosclerosis and proteinuria by reducing TGF-β1 expression and hence matrix production.
Formation and Retention of Cotinine during Placental Transfer of Nicotine in Human Placental Cotyledon
Authors: Sastry B.V. Rama , Chance M.B. , Hemontolor M.E. , Goddijn-Wessel T.A.W. 
Published: April 2003

Maternal smoking during pregnancy causes reduction of fetal breathing movements, an effect attributed to nicotine in fetal blood. Nicotine is metabolized to cotinine which has a long plasma half-life and exhibits slow clearance across membrane barriers. It is also known to activate placental phospholipase-A<sub>2</sub>-like enzymes, resulting in formation of prostaglandins. Therefore, we studied transport of nicotine in isolated perfused cotyledon of normal human term placenta. The placental cotyledon was perfused with aerated (21% O<sub>2</sub>, 5% CO<sub>2</sub>) Krebs-Ringer bicarbonate buffer (pH 7.4, 37°C) containing 2% albumin on both maternal (230 ml, 15 ml/min, 35 mm Hg) and fetal (93 ml, 1.75 ml/min, 70 mm Hg) sides in a closed recirculating system. Nicotine (2 mg) was added to the maternal perfusate; perfusate samples (1 ml) were collected from both sides at regular intervals and analyzed for nicotine and cotinine by high-pressure liquid chromatography. This study gave the following results: (1) In about 60–80 min, 18.6% of the nicotine added to the maternal perfusate was transferred to the fetal perfusate, and the maternal/fetal concentration ratio reached 1.0. These results show rapid placental transfer of nicotine, consistent with its high lipid solubility. (2) Less than 1% is metabolized to cotinine in placenta. The ratio of cotinine concentrations in maternal and fetal perfusates reached 1.0 in about 40 min. These studies were also verified using <sup>14</sup>C-nicotine. (3) Maximal reduction in fetal breathing movements occurs at about 30 min, and recovery occurs at 90 min after tobacco smoking by the mother. These observations agree with the rate of placental transfer of nicotine. (4) When nicotine was added on the fetal side, part of it was metabolized to cotinine. However, the maximal concentration of cotinine was twice higher on fetal than on maternal side. These observations suggest that accumulation of cotinine on fetal side may activate prostaglandin formation and trigger spontaneous abortions in pregnant smokers.
Effects of Ketorolac on Bone Repair: A Radiographic Study in Modeled Demineralized Bone Matrix Grafted Rabbits
Authors: Ho Mei-Ling , Chang Je-Ken , Wang Gwo-Jaw 
Published: April 2003

The effects of ketorolac on bone repair were studied radiographically. The effects of methylprednisolone were also compared. Demineralized bone matrix was grafted into the fractured gap of rabbit’s ulna as an experimental bone repair model. The rabbits received ketorolac 2 or 4 mg/kg body weight daily for 6 weeks after transplantation. Serial radiographic studies were performed 2, 4, and 6 weeks after transplantation. Mineralization of grafts and bone union were evaluated as the parameters of bone repair. Comparing the bone repair among groups at individual time points, ketorolac-treated groups showed no statistical differences as compared with the control group in either mineralization or bone union, whereas methylprednisolone significantly suppressed both parameters. However, comparing the mineralization during the healing process in each group, the control group and the group treated with ketorolac 2 mg/kg showed a significant increase during the period from the 2nd to the 4th week of medication, whereas both the group treated with ketorolac 4 mg/kg and the methylprednisolone-treated group showed no significant increase during this period. This poor mineralization of grafted bone in repair process affected by ketorolac suggests that 4 mg/kg of ketorolac might delay the endochondral ossification process during the period from the 2nd to the 4th week of fracture healing.
Effect of Desmethyl Tirilazad, Dizocilpine Maleate and Nimodipine on Brain Nitric Oxide Synthase Activity and Cyclic Guanosine Monophosphate during Cerebral Ischemia in Rats
Authors: del Pilar Fernandez Maria , Meizoso Maria Jose , Lodeiro Maria Jose , Belmonte Angel 
Published: April 2003

The present study was designed to evaluate the effects of pretreatment with a combination of desmethyl tirilazad (21-aminosteroid) plus dizocilpine maleate (N-methyl-<i>D</i>-aspartate receptor antagonist) and nimodipine (calcium channel antagonist) on constitutive nitric oxide synthase (cNOS) activity and cyclic guanosine monophosphate (cGMP) levels in brain homogenates of rats subjected to global cerebral transient ischemia induced by bilateral clamping of the carotids for 30 min and reduction of arterial pressure (to 50–60 mm Hg) by intravenous infusion of trimethaphan (30 mg/kg). Our results show that cerebral ischemia produced an increase in cNOS activity and cGMP levels in brain homogenates. Pretreatment with desmethyl tirilazad or dizocilpine maleate or nimodipine individually significantly suppressed (p < 0.01) the increase in cNOS activity and cGMP levels induced by cerebral ischemia, which may be related to their neuroprotective effect. Similar results were obtained with pretreatment by a combination of desmethyl tirilazad plus dizocilpine maleate plus nimodipine.
Antiallergic Action of Betotastine Besilate (TAU-284) in Animal Models: A Comparison with Ketotifen
Authors: Ueno Makoto , Inagaki Naoki , Nagai Hiroich , Koda Akihide 
Published: April 2003

The effects of betotastine besilate (betotastine: TAU-284), a novel antiallergic drug, on homologous passive cutaneous anaphylaxis (PCA), mediator-induced cutaneous reaction, antigen-induced asthmatic responses and platelet-activating factor (PAF)-induced airway eosinophilia in several animal models, were compared to ketotifen. Betotastine (0.1 mg/kg, p.o.) and ketotifen (1 mg/kg, p.o.) inhibited both rat PCA and histamine-induced cutaneous reaction, whereas they showed little effect on serotonin-induced cutaneous reaction. Betotastine (0.3 mg/kg, p.o.) and ketotifen (1 mg/kg, p.o.) significantly inhibited antigen-induced bronchoconstriction in guinea pigs which had been passively sensitized with guinea pig IgE antibody. In actively sensitized guinea pigs, the immediate and late phase increase in airway resistance (R<sub>rs</sub>) were observed within 5 min and between 4 and 7 h after the aeroantigen challenge. Betotastine (1 mg/kg, p.o.) inhibited both responses. Ketotifen (1 mg/kg, p.o.) inhibited the immediate phase response, but did not affect the late phase response. Exposure of guinea pigs to aerosolized PAF increased the number of eosinophils in bronchoalveolar lavage fluid 24 h after the stimulation. Betotastine (3–10 mg/kg, p.o.) dose-dependently inhibited PAF-induced accumulation of eosinophils in the bronchoalveolar cavity. In contrast, cetirizine (10 mg/kg, p.o.) showed a tendency to inhibit eosinophil accumulation, and ketotifen (10 mg/kg, p.o.) and terfenadine (10 mg/kg, p.o.) did not have any affect. These results indicate that betotastine could be useful in the treatment of allergic disease such as bronchial asthma.
Enhancement of Morphine Antinociception by Ibogaine and Noribogaine in Morphine-Tolerant Mice
Authors: Sunder Sharma Shyam , Bhargava Hemendra N. 
Published: April 2003

The effects of ibogaine, an alkaloid isolated form the bark of the African shrub, <i>Tabernathe iboga</i>, and noribogaine, a metabolite of ibogaine, on morphine antinociception were determined in male Swiss-Webster mice. Mice were rendered tolerant to morphine by implanting them with a pellet containing 25 mg of morphine base for 3 days. Placebo pellet-implanted mice served as controls. The antinociception of morphine (10 mg/kg, s.c.) was determined alone or in combination with an appropriate dose of ibogaine or noribogaine. Tolerance to morphine developed as a result of morphine pellet implantation as evidenced by decreased antinociceptive response to morphine. Both ibogaine and noribogaine dose-dependently enhanced morphine antinociception in morphine-tolerant but not in morphine-naive mice. It is concluded that ibogaine and noribogaine enhance morphine antinociception in morphine-tolerant mice.
Effects of Morin on an Experimental Model of Acute Colitis in Rats
Authors: Ocete M. Angeles , Gálvez Julio , Crespo M. Esperanza , Cruz Torcuata , González Mercedes , Torres M. Isabel , Zarzuelo Antonio 
Published: April 2003

The flavonoid morin was tested for anti-inflammatory activity in trinitrobenzenesulfonic acid (TNBS)-induced rat colitis. Rats were pretreated orally with several doses of the flavonoid (5, 10, 25, 100 and 200 mg/kg) 48, 24 and 1 h before and 24 h after colitis induction and examined for colonic damage 48 h after colitis induction. Colonic inflammation was characterized by diffuse hemorrhagic necrosis of the mucosa, bowel wall thickening, impairment of fluid absorption, increase in myeloperoxidase (MPO) activity, enhanced leukotriene B<sub>4</sub> (LTB<sub>4</sub>) synthesis, glutathione depletion and increased levels of malonyldialdehyde (MDA). Morin treatment, at doses ranging from 10 to 200 mg/kg, significantly reduced colonic macroscopic damage. This beneficial effect was also confirmed by inhibition of colonic MPO activity. Several mechanisms may contribute to the protective effect exerted by morin. First, inhibition of colonic LTB<sub>4</sub> synthesis is a common feature for all the active doses of the flavonoid. Second, the antioxidant properties of morin, which partially prevented colonic glutathione depletion (at doses of 10 and 25 mg/kg) or inhibited colonic MDA production (at doses of 100 and 200 mg/kg), can collaborate in preventing TNBS-induced inflammation.