bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transoesophageal Echocardiography in Patients without Arterial and Major Cardiac Sources of Embolism: Difference between Stroke Subtypes
Authors: Cerrato P. , Imperiale D. , Priano L. , Mangiardi L. , Morello M. , Marson A.M. , Carrà F. , Barberis G. , Bergamasco B. 
Published: April 2003

We studied the records of 175 consecutive patients referred to our neurologic ward between January 1994 and February 2000 with a diagnosis of ischaemic cerebrovascular disease (ICVD) (stroke or transient ischaemic attack – TIA) who underwent transoesophageal echocardiography (TEE). We excluded patients with large vessel disease, high-risk embolic cardiopathies and other rare causes of stroke. According to clinical and neuroimaging findings, patients were divided into two groups. The lacunar (LAC) group (69/175 (39.4%)) and the nonlacunar (N-LAC) one (106/175 (60.6%)). The control population consisted of 78 consecutive patients, referred to the echocardiography laboratory for TEE without history of ICVD and known heart disorders. Patent foramen ovale (PFO) frequency was significantly higher in case patients than in control subjects (55/175 (31.4%) vs. 13/78 (16.6%); p = 0.02). Among case patients, PFO was more prevalent in the N-LAC group than in the LAC one (43/106 (40.6%) vs. 12/69 (17.4%); p = 0.0005). A large degree of shunt occurred in 53.5% of N-LAC patients and in 16.7% of LAC ones (p = 0.04). Atrial septal aneurysm (ASA) was detected in 12% of case patients and 1.3% of control subjects (p = 0.003) and was more frequent in the N-LAC group than in the LAC one (16 vs. 5.8%; p = 0.05). Mitral prolapse (MP) was present in 6/175 (3.4%) ICVD patients (vs. 1/78 among controls) in most cases associated with myxomatous valve redundancy. Aortic arch atheromas (AA) were detected in 12% of ICVD patients and in 10.2% of controls. The frequency was 9.4% in N-LAC and 15.9 in LAC. No complicated AA (plaque thickness >4 mm, ulcerated atheroma, superimposed thrombus) were detected. After multivariate analysis, PFO (OR = 3.8; 95% CI = 2.7–7.9) and ASA (OR = 8.01; 95% CI = 3.0–16.1) appeared to be independent predictors of ICVD. PFO (OR = 2.24; 95% CI = 1.24–4.92) was also independently associated with N-LAC stroke subtype and its importance was even higher in younger patients. Our study provides further evidence that TEE is a helpful diagnostic tool in stroke patients without arterial and major cardiac sources of embolism. However, its utility differs according to type and localization of the ischaemic lesion being more relevant in patient with N-LAC infarctions.
High Density Culturing of Porcine Hepatocytes Immobilized on Nonwoven Polyurethane-Based Biomatrices
Authors: Pahernik S.A. , Thasler W.E. , Doser M. , Gomez-Lechon M.J. , Castell M.J. , Planck H. , Koebe H.G. 
Published: April 2003

<i>Objective:</i> Hepatocytes are increasingly used as functional units in bioartificial liver devices. The objective of the present study was to investigate the feasibility of culturing porcine hepatocytes in high density on a novel polyurethane-based nonwoven three-dimensional matrix. We investigated (1) the optimal cell density within this culture configuration, (2) the maintenance of liver-specific morphology and cell functions over long-term periods and (3) the necessity to apply an additional extracellular matrix component (collagen gel). <i>Methods:</i> Nonwoven polyurethane matrices were manufactured by a specially developed fiber extrusion technology. Pig hepatocytes were cultured at various cell densities of 0.1, 0.25, 0.5, 0.75, 1 and 2 × 10<sup>6</sup> cells/cm<sup>2</sup> on three-dimensional networks of nonwoven polyurethane matrices and cell adhesion as well as functional parameters (DNA of nonattached/attached cells, lactate dehydrogenase release and cytochrome P450 activity) were determined. To assess the performance of cells within this configuration albumin and urea excretion was measured over 8 days. The potentially beneficial effect of an additional extracellular matrix configuration was evaluated by comparing the average albumin synthesis in groups of identical cell numbers. <i>Results:</i> The optimal cell density in this three-dimensional culture configuration was 1 × 10<sup>6</sup> cells/cm<sup>2</sup>. The functional capacity of hepatocytes was stable for 8 days at an average level of 53.7 ± 5.6 ng/h/µg DNA and of 1.8 ± 0.14 µg/h/µg DNA for albumin and urea excretion, respectively. The supplementation of an extracellular matrix configuration did not improve functional activity of cells. Average albumin synthesis was 35.6 ng/h/µg DNA (28.7, 42.8) and 32.7 ng/h/µg DNA (23.4, 49.2) for collagen-immobilized and control cultures, respectively. <i>Conclusion:</i> The results of the study indicate that nonwoven polyurethane sheets supply a biocompatible support structure for functionally active high density cultures. Thus, nonwoven polyurethane matrices should be further investigated on with respect to their role in the development, optimization and design of bioartificial liver systems.
Apoptosis in Cultured Rat Islets of Langerhans and Occurrence of Bcl-2, Bak, Bax, Fas and Fas Ligand
Authors: Hanke J. 
Published: April 2003

Isolated Langerhans islets are widely used for diabetic transplantation experiments and investigations of the mechanisms leading to the death or survival of insulin-producing cells in cultured islets. The present study was aimed at investigating programmed cell death and the role of apoptosis-associated peptides in insulin and glucagon cells of islets isolated from untreated rats and held in cultured suspension. Islets were removed from medium on days 0, 7, 14, 21 and 29, embedded in Epon, and semi-thin serial sections were prepared. At designated intervals, histologic sections were treated with the direct fluorescein-labelled TUNEL method and immunostained for pancreatic hormones (glucagon, insulin) and apoptotic peptides [Bak, Bax, Fas, Fas ligand (FasL)], as well as for the anti-apoptotic peptide Bcl-2. All tissue sections were investigated using confocal laser scanning microscopy under identical setting for semiquantitative estimation of staining intensity. The percentage of apoptotic cells was between 1.6 and 2.1% and most apoptotic cells were beta-cells. Corresponding cells often contained Bak and Bax. Fas and FasL were mostly detected in islet cells within the first week after preparing the cultured suspension. The insulin content was low (1.1 ± 0.22 ng per islet) directly after isolation. It then increased progressively up to day 14, after which it began to decrease. Glucagon expression, on the other hand, remained high for the entire duration of the investigation. In conclusion, the islet beta-cells may recover after the isolation procedure, but after 4 weeks in culture, both the insulin content and Bcl-2 staining decrease. Moreover, apoptosis is mediated by different mechanisms after the isolation procedure and after culturing the islets for 1 month. The present data may be important for further studies on isolated, cultivated or transplanted islets.
Ultrastructural Study of Anterograde Transport of Glial Cell Line-Derived Neurotrophic Factor from Dorsal Root Ganglion Neurons of Rats towards the Nerve Terminal
Authors: Ohta Keisuke , Inokuchi Tetsuo , Gen Eizo , Chang Jaekwang 
Published: April 2003

The glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic substance in the central and peripheral nervous systems. The present immunohistochemical study clarified the ultrastructural localization of GDNF-immunoreactive substance (GDNF-IR) accumulated at transfected sciatic nerve stumps and also at normal spinal dorsal horn, and has demonstrated that GDNF-IR products appear to be located in dense-cored vesicles within the axons. Furthermore, to determine the source of proximally accumulated GDNF in the transected sciatic nerve, we attempted a transection and a double ligation maneuver involving the sciatic nerve. In the early period after the ligation (20 h), GDNF-IR fibers were observed in the proximal and distal segment of the ligations, but no immunoreactivities were detected in the middle segment. On the other hand, at a late period (8 days) after the transection, GDNF-IR fibers had almost disappeared, but weak GDNF-IR was observed in Schwann cells in the proximal and distal stumps of transected nerve. These findings suggest that most of GDNF-IR was transported from the proximal or distal side in the early period, but was locally synthesized by Schwann cells around the ligations in the late period. Spinal rhizotomy caused prominent accumulation of GDNF-IR products at the cut end of the ganglion side of the dorsal root, but not at the ventral root. These results suggested that dorsal root ganglionic (DRG) sensory neurons are one of the origins of GDNF. The fact that small- to medium-sized DRG neurons show enhanced GDNR-IR after the colchicine treatment may support the above suggestion. In conclusion, the present results strongly suggest that a subgroup of DRG sensory neurons synthesized GDNF-containing dense-cored vesicles in the neuronal somata and anterogradely transports the vesicles to peripheral or central axon terminals.
Uterine Artery Doppler Velocimetry in Patients with Idiopathic Hydramnios
Authors: Hershkovitz R. , Sheiner E. , Furman B. , Smolin A. , Hallak M. , Mazor M. 
Published: April 2003

<i>Objective:</i> To evaluate the role of overdistended uterus on the uterine artery (UA) blood flow velocimetry by comparing UA Doppler in patients with idiopathic hydramnios to patients with normal amniotic fluid (AF) volume. <i>Methods: </i>Pulsatility index (PI) of both UAs was determined prospectively between 26 and 41 weeks of gestation in 72 consecutive pregnant women with singleton pregnancies and idiopathic hydramnios and in 72 pregnant women with normal AF volume. Hydramnios was defined as an AF index (AFI) above 24 cm. A normal amount of AF was defined as an AFI of 6–24 cm. Patients with known fetal structural or chromosomal anomalies and those with diabetes mellitus were excluded. <i>Results: </i>No significant differences were observed between the groups with regard to maternal age, gravidity, and gestational age at examination. Gestational age at delivery and accordingly birth weight were significantly lower in patients with hydramnios compared to those with a normal AFI (34.9 ± 2.1 vs. 39.1 ± 1.2, p < 0.001; 2,508 ± 399 vs. 2,995 ± 420, p < 0.001, respectively). No significant differences were noted between right UA PI (0.73 ± 0.3 in the hydramnios group vs. 0.71 ± 0.2 in the control group; p = 0.091) and left UA PI (0.91 ± 0.3 in the hydramnios group vs. 0.84 ± 0.3 in the control group; p = 0.131) of both groups. <i>Conclusion: </i>UA velocimetry in patients with idiopathic hydramnios was not significantly different from those with a normal AF volume.
Effects of Urinary Trypsin Inhibitor in Patients at Risk for Premature Labor with a Bulging Fetal Membrane
Authors: Matsuda Yoshio , Yunohara Naoki 
Published: April 2003

<i>Objective: </i>To investigate the effect of urinary trypsin inhibitor (UTI) in patients at risk for premature labor with bulging membrane. <i>Methods: </i>Patients who had developed a bulging membrane from 22 to 27 weeks and 6 days of gestation were studied. These cases were divided into two types based on the severity: those with a moderately developed bulging membrane like a ‘dome’ (dome type), and those with a membrane prolapsed into the vagina, resulting in an ‘hourglass’ shape (hourglass type). We compared the outcomes of treatment with or without UTI (UTI group versus non-UTI group) in each type. Gestational age at delivery, birth weight, prolongation time from admission to delivery, and neonatal mortality rate were examined in each group. <i>Results: </i>A total of 43 patients with a bulging membrane were analyzed. In 21 patients with the dome type, gestational age at delivery (the UTI group versus the non-UTI group; 30.4 ± 5.0 versus 26.4 ± 1.9 weeks, p < 0.05), birth weight (1,436.8 ± 708.3 versus 882.8 ± 261.6 g, p < 0.05) and neonatal mortality rate (0/13 versus 3/8, p < 0.05) were all significantly improved by the use of UTI. On the other hand, in 22 patients with the hourglass type, there was no significant difference between the UTI group and the non-UTI group. The overall prevalence of histological chorioamnionitis was 60%. <i>Conclusion: </i>These results suggest that UTI therapy is very effective in patients at risk for premature labor with a moderately developed bulging membrane during the second trimester.
Dehydroepiandrosterone Sulfate Treatment for Atrichia pubis
Authors: Wit Jan-Maarten , Langenhorst Veerle J. , Jansen Maarten , Oostdijk Wilma , van Doorn Jaap 
Published: April 2003

<i>Objective:</i> To evaluate the efficacy of oral dehydroepiandrosterone sulfate (DHEAS) treatment for atrichia pubis in female adolescents. <i>Study Design:</i> Two XY female adolescents with 17-hydroxylase deficiency and 2 XX females with panhypopituitarism presenting with atrichia pubis were treated with a daily dosage of DHEAS 10 mg/m<sup>2</sup> body surface in addition to their regular substitution therapy. The dosage was increased according to clinical response. Pubic hair stages, growth and serum DHEAS were evaluated and in 1 case also serum IGFs and IGFBPs. <i>Results:</i> A dosage of 10 mg/m<sup>2</sup> for 1 year led to serum DHEAS levels at the lower limit of the normal range. 15 mg/m<sup>2</sup> was needed to achieve pubic hair stage 4–5 and axillary hair in patients with 17-hydroxylase deficiency. In panhypopituitarism, pubic hair developed at a slower pace and reached stage 4 on a dosage of 25– 30 mg/m<sup>2</sup>. Baseline serum IGF-I SDS was –0.67 and did not change on the initial dosage of DHEAS, in combination with submaximal estrogen substitution (10 µg ethinyl estradiol). On the combination of 15 mg/m<sup>2</sup> DHEAS and full estrogen substitution, IGF-I SDS increased to an average of –0.15. IGFBP-3 SDS increased from 1.4 to a mean of 2.6 in the first year, and went back to 1.4 in the second year. IGFBP-6 SDS was low at baseline (–2.5) and rose to –1.9 and –1.7 IGF-II and IGFBP-1 showed an irregular pattern. <i>Conclusions:</i> Oral administration of DHEAS in a dosage of 15 mg/m<sup>2</sup> o.d. is an efficacious treatment for atrichia pubis. For females with a panhypopituitarism a higher dosage appears needed. Given this and other biological actions of DHEAS, substitution therapy with DHEAS or DHEA to females with adrenal androgen deficiency appears rational.
Identification of Cross-Reactive Proteins amongst Different <i>Curvularia</i> Species
Authors: Gupta Ratna , Singh Bhanu P. , Sridhara Susheela , Gaur Shailendra N. , Kumar Raj , Chaudhary Vijay K. , Arora Naveen 
Published: April 2003

<i>Background:</i><i>Curvularia lunata</i> is an important inhalant allergen. The present study was undertaken to investigate the shared IgG- and IgE-binding components among seven <i>Curvularia</i> species prevalent in the aerospora. <i>Methods:</i> Seven different <i>Curvularia</i> species were grown in a semisynthetic medium for 13 days. The extracts were analyzed by SDS-PAGE, immunoblot and ELISA/immunoblot inhibition using sera from <i>C. lunata</i>-positive patients and anti-<i>C. lunata</i> rabbit serum. <i>Results:</i> Different <i>Curvularia</i> species showed 11–19 protein bands on SDS-PAGE. Proteins of 12, 20, 31, 45, 53, 78 and 97 kD were present in all the species. Eight out of 98 nasobronchial patients exhibited positive skin tests to <i>C. lunata</i> and to at least five <i>Curvularia</i> species. ELISA using these sera showed IgE binding with <i>Curvularia</i> species. Immunoblot using pooled anti-<i>C. lunata</i> sera from patients showed 5–12 allergenic proteins. Proteins of 12, 31, 45, 53 and 78 kD showed IgE binding in <i>Curvularia</i> species. Antibodies against <i>C. lunata</i> detected 6–14 antigenic proteins on immunoblot. Proteins of 31, 45 and 53 kD showed IgG binding in all the species. Proteins of 31 and 53 kD showed complete IgE/IgG binding inhibition. IgE/IgG ELISA inhibition showed dose-dependent inhibition in <i>Curvularia</i> species. <i>C. lunata</i> extract required 0.17 and 0.11 µg of protein for 50% IgE and IgG inhibition, respectively. <i>C. clavata</i> and <i>C. pallescens</i> required 10 times more protein to exhibit the same inhibition and other species required similar protein levels as those required by <i>C. lunata.</i><i>Conclusions:</i> A high degree of cross-reactivity was observed between <i>C. lunata</i> and the six other <i>Curvularia</i> species tested. <i>C. lunata</i> and <i>C. senegalensis</i> shared maximum allergenic and antigenic components.
Hydrogen Peroxide Reverses IL-5 Afforded Eosinophil Survival and Promotes Constitutive Human Eosinophil Apoptosis
Authors: Kankaanranta Hannu , Giembycz Mark A. , Barnes Peter J. , Haddad El-Bdaoui , Saarelainen Seppo , Zhang Xianzhi , Moilanen Eeva , Lindsay Mark A. 
Published: April 2003

<i>Background:</i> Eosinophils play a central role in the induction and perpetuation of allergic inflammatory responses. The present study was performed to investigate the effects of reactive oxygen intermediates on constitutive apoptosis as well as on interleukin (IL)-5 afforded human eosinophil survival. <i>Methods:</i> Peripheral blood eosinophils were isolated by CD16-negative selection to >99% purity and were cultured for 48 h. The number of apoptotic eosinophils in the culture was assessed by flow cytometric analysis of relative DNA content in propidium-iodide-stained cells, annexin-V binding or by morphological analysis. Apoptosis was confirmed by the appearance of a typical ladder pattern in the DNA fragmentation assay by agarose gel electrophoresis. <i>Results:</i> Exogenous H<sub>2</sub>O<sub>2</sub> reversed IL-5-afforded eosinophil survival by inducing apoptosis. Constitutive eosinophil apoptosis was inhibited by a reduction of intracellular levels of H<sub>2</sub>O<sub>2</sub> by catalase. Exogenous H<sub>2</sub>O<sub>2</sub> increased the rate of constitutive apoptosis. <i>Conclusions:</i> Our results suggest that H<sub>2</sub>O<sub>2</sub> may play a role in the downregulation of eosinophilic inflammation by inducing eosinophil apoptosis.
Intravenous Ulinastatin Therapy for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Pediatric Patients
Authors: Inamo Yasuji , Okubo Takahiro , Wada Mika , Fuchigami Sachiko , Hashimoto Kouji , Fuchigami Tatsuo , Takahashi Shigeru , Sawada Shigemasa , Harada Kensuke 
Published: April 2003

<i>Background:</i> More effective therapy is needed for the treatment of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The clinical efficacy of intravenous ulinastatin therapy was investigated in 3 Japanese pediatric patients with SJS or TEN. <i>Methods:</i> Ulinastatin was given to 1 pediatric SJS patient and 2 pediatric TEN patients within 7 days (patient 1; SJS), 6 days (patient 2; TEN), or 4 days (patient 3; TEN) after the onset of the skin rash. Ulinastatin was administered intravenously at a dose of 7,500 U/kg/day (maximum dose: 300,000 U/day). No corticosteroids were given. After the skin lesions resolved, the ulinastatin dose was reduced to between 2,500 and 5,000 U/kg/day as maintenance therapy and then the drug was withdrawn. <i>Results:</i> Erythema, fatigue, and fever improved within 12–36 h of starting the ulinastatin infusion, and the skin lesions resolved completely after 4–7 days of ulinastatin therapy. None of the patients had cutaneous or ocular sequelae. No patient developed secondary infection or relapse and ulinastatin therapy caused no side effects. <i>Conclusion:</i> Ulinastatin dramatically reduced the febrile period with no adverse effects and was very safe in this study. Ulinastatin appears to be a useful and effective therapy for controlling SJS and TEN without sequelae.
Selective Estrogen Receptor Modulator Effects in the Rat Brain
Authors: Zhou Wenxia , Koldzic-Zivanovic Nina , Clarke Charlotte H. , de Beun René , Wassermann Karsten , Bury Paul S. , Cunningham Kathryn A. , Thomas Mary L. 
Published: April 2003

The effects in the brain of selective estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene have not yet been fully elucidated. Based upon the hypothesis that serotonin (5-HT)-steroid hormone interactions are important in mood regulation, we have compared six SERMs (tamoxifen, raloxifene, levormeloxifene, NNC 45-0781, NNC 45-0320, NNC 45-1506) with 17β-estradiol (E<sub>2</sub>) in terms of their ability to regulate mRNA levels of estrogen receptor (ER)α, ERβ, 5-HT<sub>1A</sub> receptor, and 5-HT reuptake transporter (SERT) in the midbrain, amygdala, and hypothalamus of ovariectomized (OVX) rats. Female rats (n = 6/group, 8 groups total) were OVX and allowed to recover for 2 weeks. During the third post-OVX week, rats were injected subcutaneously with E<sub>2</sub> (0.1 mg/kg) or one of the SERMs (5 mg/kg) once per day for 7 days. Twenty-four hours after the last injection, tissue was collected for the determination of mRNA levels by ribonuclease protection assay (RPA). E<sub>2</sub> treatment significantly decreased mRNA levels for ERα, ERβ, and SERT in midbrain and ERα in hypothalamus. Tamoxifen increased ERβ mRNA levels in hypothalamus, while raloxifene increased ERβ mRNA levels in amygdala. NNC 45-0320 decreased ERα mRNA in hypothalamus and decreased ERβ mRNA in amygdala. These results suggest that while SERMs are not full estrogen receptor agonists in the brain, the agonist/antagonist profiles for individual SERMs may differ among brain areas. This raises the possibility of developing new SERMs for selective functions in specific brain areas.
Evidence for a Central Inhibitory Role of Growth Hormone Secretagogues and Ghrelin on Gastric Acid Secretion in Conscious Rats
Authors: Sibilia V. , Pagani F. , Guidobono F. , Locatelli V. , Torsello A. , Deghenghi R. , Netti C. 
Published: April 2003

We examined the possible central and peripheral effects of synthetic growth hormone secretagogues (GHS), hexarelin (Hexa) and EP 40737 (D-Thr-D-Trp (2-Me)-Ala- Trp-D-Phe-Lys-NH<sub>2</sub>), and of their endogenous counterpart, ghrelin, on gastric acid secretion. The compounds were administered intracerebroventricularly (i.c.v.) or subcutaneously (s.c.) in conscious male rats and the volume of gastric secretion and gastric acid output were examined 3 h after pylorus ligation (Shay-test). Central Hexa, EP 40737 and ghrelin administration (from 0.1 pmol to 1 nmol/rat, i.c.v.) significantly inhibited gastric acid secretion. The maximum inhibitory effect on gastric acid output was detected at the dose of 10 pmol/rat, i.c.v. for Hexa (–51.3%), of 100 pmol/rat, i.c.v. for EP 40737 (–70%) and of 1 pmol/rat, i.c.v. for ghrelin (–60%). All peptides were less effective at the highest dose used (1 nmol/rat, i.c.v.). Hexa, EP 40737 and ghrelin injected s.c. did not modify gastric acid secretion. The inhibitory action of Hexa on gastric acid secretion seems to involve brain somatostatinergic system since Hexa (10 pmol/rat, i.c.v.) did not inhibit gastric acid secretion in rats pretreated (4 h before) with cysteamine (300 mg/kg, s.c.), a depletor of endogenous somatostatin. These results show that synthetic GHS and ghrelin exert a central long-lasting inhibitory effect on gastric acid secretion in conscious pylorus-ligated rats. The fact that very low doses of ghrelin and GHS inhibit gastric secretion, provide evidence for a tonic inhibitory role of the peptides in the central control of gastric secretory function.