bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diazepam Stimulates Migration and Phagocytosis of Human Neutrophils: Possible Contribution of Peripheral-Type Benzodiazepine Receptors and Intracellular Calcium
Authors: Marino Franca , Cattaneo Simona , Cosentino Marco , Rasini Emanuela , Di Grazia Laura , Fietta Anna Maria , Lecchini Sergio , Frigo Gianmario 
Published: April 2003

In isolated human neutrophils, diazepam (10 nmol/l to 10 µmol/l) concentration-dependently increased migration and phagocytosis. Diazepam-induced migration and phagocytosis were inhibited by the peripheral benzodiazepine receptor (PBR) antagonist PK11195 (10 µmol/l). The PBR agonist Ro5-4864 (10 nmol/l to 10 µmol/l) did not affect migration but slightly enhanced phagocytosis, while clonazepam, which binds to the central-type benzodiazepine receptors but has no affinity for PBRs, was ineffective on both parameters up to 10 µmol/l. Phagocytosis induced by diazepam or Ro5-4864 was inhibited by the Ca<sup>2+</sup> channel blocker <i>L</i>-verapamil (10 µmol/l), which however did not affect the action of diazepam on migration. Competition binding experiments performed by fluorescent staining of PBRs showed that diazepam directly interacts with PBRs on human neutrophils. Both diazepam and Ro5-4864 (10 nmol/l to 10 µmol/l) induced a rise of intracellular free Ca<sup>2+</sup> concentrations ([Ca<sup>2+</sup>]<sub>i</sub>), which was inhibited by PK11195 (10 µmol/l) and <i>L</i>-verapamil (10 µmol/l) and prevented by extracellular Ca<sup>2+</sup> chelation with EGTA (5 mmol/l). In conclusion, experimental evidence indicates that in human neutrophils diazepam stimulates both migration and phagocytosis through activation of PBRs. Diazepam-induced [Ca<sup>2+</sup>]<sub>i</sub> changes depend on a PBR-operated, <i>L</i>-verapamil-sensitive increase in the plasma membrane permeability and subsequent extracellular Ca<sup>2+</sup> entry, and contribute to diazepam-induced phagocytosis. On the contrary, the effect of diazepam on migration seems to occur through Ca<sup>2+</sup>-independent mechanisms.
Gastroprokinetic Effect and Mechanism of SK-896, a New Motilin Analogue, during the Interdigestive Period in Conscious Dogs
Authors: Tsukamoto Katsura , Tagi Yoshihiko , Nakazawa Toru , Takeda Motohiro 
Published: April 2003

SK-896 [(Leu<sup>13</sup>)motilin-Hse] is a new human motilin analogue synthesized from <i>Escherichia coli</i> using a biotechnological method. We investigated the gastrointestinal motor-stimulating effect of SK-896 and the mechanism of this effect using implanted force transducers in conscious dogs. Infusion of SK-896 during phase I in the interdigestive state induced interdigestive migrating contractions like motility in the gastroduodenum. The motility index (MI<sub>0–20</sub>) of gastric antrum motor activity induced by SK-896 was increased dose dependently (r = 0.830, p < 0.001), and the MI<sub>0–20</sub> induced by SK-896 at a dose of 0.25 µg/kg/h for 20 min was the same as that for spontaneous phase III contractions. The SK-896-induced MI<sub>0–20</sub> was significantly decreased by atropine, hexamethonium, dopamine, granisetron, and yohimbine. Conversely, ketanserin, phentolamine, timolol, and naloxone did not have significant effects on SK-896-induced MI<sub>0–20</sub>. The effects of these drugs on human motilin (0.25 µg/ kg/h for 20 min) induced MI<sub>0–20</sub> were the same as those of SK-896. These results indicate that SK-896 induces gastrointestinal motility during the interdigestive period in dogs with regulation of acetylcholine release from the cholinergic nerve terminal via the parasympathetic nervous system in the same fashion as human motilin.
Partial Agonistic Properties of (±)-Pindolol at Atypical β-Adrenoceptors in the Guinea Pig Gastric Fundus
Authors: Horinouchi Takahiro , Koike Katsuo 
Published: April 2003

(±)-Pindolol ([1-(1H-indol-4-yloxy)-3-[(1-methylethyl)- amino]-2-propanol)]) is a partial agonist at atypical β-adrenoceptors in the guinea pig gastric fundus. (±)-Pindolol induced concentration-dependent relaxation in this tissue. However, the relaxant responses of (±)-pindolol were not antagonized by a combination of the selective β<sub>1</sub>-adrenoceptor antagonist atenolol (10<sup>–4</sup> mol/l) and the selective β<sub>2</sub>-adrenoceptor antagonist butoxamine (10<sup>–4</sup> mol/l). In the presence of both atenolol and butoxamine, the nonselective β<sub>1</sub>-, β<sub>2</sub>- and β<sub>3</sub>-adrenoceptor antagonist (±)-bupranolol (10<sup>–5</sup>–10<sup>–4</sup> mol/l) caused a concentration-dependent rightward shift of the concentration-response curves for (±)-pindolol. Schild plot analyses of (±)-bupranolol against (±)-pindolol gave the pA<sub>2</sub> value of 5.46 ± 0.03 and Schild slope was not significantly different from unity. Furthermore, (±)-pindolol (10<sup>–5</sup> mol/l) weakly but significantly antagonized the relaxant responses to catecholamines ((–)-isoprenaline, (–)-noradrenaline and (–)-adrenaline), a selective β<sub>3</sub>-adrenoceptor agonist BRL37344 ((R*,R*)-(±)-4-[2-[(2-(3-chlorophenyl)-2-hydroxyethyl)amino]propyl]phenoxyacetic acid sodium salt) and a nonconventional partial β<sub>3</sub>-adrenoceptor agonist (±)-CGP12177A ([4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one] hydrochloride). These results suggest that (±)-pindolol acts as a partial agonist at atypical β-adrenoceptors in the guinea pig gastric fundus.
Binding of the Active Metabolite of Chloral Hydrate, 2,2,2-Trichloroethanol, to Serum Albumin Demonstrated Using Tryptophan Fluorescence Quenching
Authors: Solt Ken , Johansson Jonas S. 
Published: April 2003

Chloral hydrate, a sedative/hypnotic agent widely used in the pediatric population, is converted to the active metabolite 2,2,2-trichloroethanol (TCE) in the liver. Tryptophan fluorescence quenching has been used previously to show that halothane and chloroform bind saturably to serum albumin, and a similar approach is used here to demonstrate that TCE also binds to albumin. TCE quenches the steady-state tryptophan fluorescence of bovine serum albumin (BSA) in a concentration-dependent, saturable manner with a K<sub>D</sub> = 3.3 ± 0.3 mmol/l. Unlike halothane and chloroform, however, TCE also elicits a concentration-dependent blue-shift in the fluorescence emission spectrum of BSA and human serum albumin. This indicates that TCE induces a conformational change in the protein, causing the tryptophan to experience a change in its chemical environment, thus shifting the peak of the emission spectrum. Circular dichroism spectroscopy revealed a decrease in the α-helical content of BSA from 65.8 ± 0.4 to 62.9 ± 0.6% when TCE was present at a concentration of 30 mmol/l, providing further evidence for a conformational change. There is evidence that TCE potentiates the action of ligand-gated ion channels such as the GABA<sub>A</sub> and 5-HT<sub>3</sub> receptors, and the present results suggest that anesthetic alcohols may act by binding to these proteins <i>and</i> inducing structural changes that may in turn alter protein function.
The Production of English Vowels by Fluent Early and Late Italian-English Bilinguals
Authors: Piske Thorsten , Flege James Emil , MacKay Ian R.A. , Meador Diane 
Published: April 2003

AbstractThe primary aim of this study was to determine if fluent early bilinguals who are highly experienced in their second language (L2) can produce L2 vowels in a way that is indistinguishable from native speakers’ vowels. The subjects were native speakers of Italian who began learning English when they immigrated to Canada as children or adults (‘early’ vs. ‘late’ bilinguals). The early bilinguals were subdivided into groups differing in amount of continued L1 use (early-low vs. early-high). In experiment 1, native English-speaking listeners rated 11 English vowels for goodness. As expected, the late bilinguals’ vowels received significantly lower ratings than the early bilinguals’ vowels did. Some of the early-high subjects’ vowels received lower ratings than vowels spoken by a group of native English (NE) speakers, whereas none of the early-low subjects’ vowels differed from the NE subjects’ vowels. Most of the observed differences between the NE and early-high groups were for vowels spoken in a nonword condition. The results of experiment 2 suggested that some of these errors were due to the influence of orthography.
Changes in Lactate and Other Ions in Plaque and Saliva after a Fluoride Rinse and Subsequent Sucrose Administration
Authors: Vogel G.L. , Zhang Z. , Chow L.C. , Schumacher G.E. 
Published: April 2003

The purpose of this study was to examine plaque and saliva composition after a fluoride rinse and subsequent sucrose application. Fifteen subjects accumulated plaque for 48 h, and then rinsed with a fluoride rinse based on 228 µg/g (ppm) Na<sub>2</sub>SiF<sub>6</sub> and some received no rinse. After 60 min, upper and lower buccal molar plaque samples and 1-min saliva samples were collected. The subjects then rinsed with 10% g/g sucrose solution, and 7 and 15 min later, a second and a third set of samples were collected. Plaque fluid and clarified saliva were then recovered from these samples by centrifugation, and the remaining plaque acid extracted. The plaque fluid, centrifuged saliva, and plaque extract samples were then analyzed using micro techniques for pH, free calcium, phosphate, organic acids (plaque fluid and saliva only) and fluoride. Considering both the fluoride rinse and no-rinse groups, the most notable compositional changes in saliva 7 min after the sucrose rinse were pH –0.40 unit, free calcium 0.42 m<i>M</i>, lactate 5.2 m<i>M</i>, phosphate –1.3 m<i>M</i>, and fluoride 2.8 µ<i>M</i>; while in plaque fluid, the corresponding changes were pH –1.59 unit, free calcium 1.5 m<i>M</i>, lactate 35 m<i>M</i>, phosphate –1.6 m<i>M</i> and fluoride –26 µ<i>M</i>. After sucrose rinsing, undersaturation was found with respect to dicalcium phosphate dihydrate in saliva and plaque fluid and with respect to tooth enamel in some plaque fluid samples. Plaque fluid composition appeared to be strongly influenced by salivary clearance, diffusive loss of ions into the water phase of the rinse, and lower jaw pooling of the sucrose and fluoride components of the rinses. After the experimental rinse, the fluoride concentration in plaque fluid [86 ± 22 m<i>M</i> (upper molar site), 162 ± 150 m<i>M</i> (lower molar site)], saliva (26 ± 18 m<i>M</i>), and whole plaque [99 ± 97 µg/g (upper molar site), 197 ± 412 µg/g (lower molar site)] was comparable to the values in previous studies using this rinse. These very high plaque fluid fluoride concentrations, compared with the ‘no-rinse’ samples, induced an approximately 0.3-unit increase in the plaque fluid pH 7 min after the sucrose rinse, a small decrease (approximately 20%) in lactate production and a modest increase in enamel saturation. Although these changes were all statistically significant, no correlation was found between the decrease in lactate concentration and plaque fluid fluoride, pH or whole plaque fluoride.
Colonic Transit Time in Diabetic and Nondiabetic Long-Term Care Patients
Authors: Ron Yishai , Leibovitz Arthur , Monastirski Nechama , Habot Beni , Segal Rephael 
Published: April 2003

<i>Background:</i> Constipation is a frequent health concern for elderly people. The increased incidence of constipation with age is mainly based on self-reported data. Only a few studies have examined this problem objectively and even fewer have carried this out in the special subpopulation of frail elderly patients. <i>Objective:</i> The aim of this study was to examine colonic transit time (CTT) in frail elderly patients. We also attempted to compare CTT in diabetics and nondiabetics within this population. <i>Methods:</i> 45 frail elderly patients, all immobile with and without diabetes mellitus, residing permanently in long-term geriatric departments were recruited for the study. All patients underwent segmental and total CTT studies using radiopaque markers. The segmental CTT was calculated separately for the four segments of the colon (ascending, transverse, descending, and rectosigmoid) and for the total transit time which was the sum of all four segments. <i>Results:</i> The average CTT was extremely prolonged in all patients included in this study. In the diabetics the CTT was even longer with a mean total transit time of 200 ± 144 h as compared with 143 ± 95 h in the controls. The difference was not statistically significant. For each segment tested, the CTT was shorter in the control group, but these differences did not reach statistical significance. <i>Conclusions:</i> The CTT is prolonged in immobile frail elderly patients. No significant differences were noted between diabetic and nondiabetic patients.
Gestational Diabetes mellitus and Neonatal Hyperthyrotropinemia
Authors: Lao Terence T. , Lee Chin-Peng 
Published: April 2003

<i>Objective:</i> To determine whether gestational diabetes mellitus (GDM) is associated with increased incidence of neonatal hyperthyrotropinemia. <i>Study Design:</i> In a retrospective study, maternal characteristics, infant outcome and cord blood thyrotropin (TSH) concentration were compared between 469 diet-treated GDM pregnancies diagnosed by the World Health Organization 75 g oral glucose tolerance test (OGTT) with 474 non-diabetic pregnancies with normal OGTT results. <i>Results:</i> Hyperthyrotropinemia (TSH >16 mIU/l) was found in 7.2% of the GDM pregnancies and 2.1% of the controls (p < 0.001), but there was no difference in the birth weight or gestational age. The TSH concentration was correlated with the OGTT 2-hour glucose value (ρ = 0.0948, p = 0.029) and Apgar score at the fifth minute (ρ = –0.1197, p = 0.009). There was no difference in the TSH or free thyroxine concentrations between the hyperthyrotropinemic newborns of the GDM and control groups. In the GDM group, the hyperthyrotropinemic newborns had a higher incidence (p = 0.017) of neonatal jaundice. <i>Conclusions:</i> Neonatal hyperthyrotropinemia is more frequently found in pregnancies with GDM, and this could have reflected increased fetal in-utero hypoxic stress in these pregnancies.
Urinary Albumin as an Indicator of Diabetic Nephropathy Lesions in Japanese Type 2 Diabetic Patients
Authors: Moriya Tatsumi , Moriya Rika , Yajima Yoshitada , Steffes Michael W. , Mauer Michael 
Published: April 2003

Caucasian type 2 diabetic patients with microalbuminuria (MA) or overt nephropathy (ON) show greater heterogeneity of renal lesions than type 1 diabetic patients. We examined whether a similar situation exists in 30 Japanese type 2 diabetic patients [21 male, age 48 ± (SD) 8 years, known duration 11 ± (SD) 8 years] without definable renal disease other than diabetic nephropathy. Six patients were normoalbuminuric (NA), 11 MA, and 13 had ON. Normal controls were 9 age-matched Japanese living-related renal transplant donors. Electron microscopic morphometry was performed on renal biopsy specimens and related to renal function. Glomerular basement membrane width and mesangial fractional volume [Vv(Mes/glom)] were increased in all type 2 diabetic patients groups (NA, MA, ON) as compared with normal controls. The Vv(Mes/glom) correlated directly with urinary albumin/creatinine. However, Vv(Mes/glom) as well as glomerular basement membrane width overlapped among the three functional categories (NA, MA, ON) and normal controls. In conclusion: (1) similar to Caucasian type 2 diabetic patients, Japanese type 2 diabetic patients have greater heterogeneity of renal structure than Caucasian type 1 diabetic patients, and (2) urinary albumin is not a reliable indicator of underlying renal structure in Japanese type 2 diabetic patients.
A Role for Hypothalamic Astrocytes in Dehydroepiandrosterone and Estradiol Regulation of Gonadotropin-Releasing Hormone (GnRH) Release by GnRH Neurons
Authors: Zwain Ismail H. , Arroyo Armando , Amato Paula , Yen Samuel S.C. 
Published: April 2003

Molecules of astrocyte origin influence gonadotropin-releasing hormone (GnRH) release and GnRH neuronal growth and differentiation. Furthermore, type 1 astrocytes express steroid receptors, presenting the possibility that steroid actions on GnRH neurons might occur via astrocytes. Utilizing GT1–7 cells, a GnRH-secreting cell line, the present study demonstrates that astrocytes mediate dehydroepiandrosterone (DHEA) or estradiol (E2) stimulated GnRH secretion. Conditioned media (CM) from astrocytes cultured for 48 h alone, with DHEA (DHEA-CM), or with E2 (E2-CM) were collected, treated with charcoal to remove steroids, and added to GT1–7 cells in culture for 12 h to test the effect on GnRH secretion. DHEA-CM and E2-CM stimulated GnRH secretion by GT1–7 cells by 4- and 3-fold, respectively. The effect of DHEA-CM on GnRH secretion by GT1–7 cells appears to be related to both DHEA and its metabolite, E2, since blocking the metabolism of DHEA into estrogen in the DHEA-treated astrocytes partially reversed the stimulatory effect of DHEA-CM. Addition of transforming growth factor (TGF)-β1-neutralizing antibody to the astrocyte cultures reversed the stimulatory effects of both DHEA-CM and E2-CM on GnRH secretion by GT1–7 cells, suggesting that TGF-β1 derived from astrocytes may be the principle mediator of E2 and DHEA effects. These data provide evidence for a novel mechanism by which circulating steroids and/or neurosteroids may modulate GnRH secretion.
Prognostic Evaluation of Preoperative Thermochemoradiotherapy for N<sub>3</sub> Cervical Lymph Node Metastases of Oral Cancer
Authors: Tohnai Iwai , Hayashi Yasushi , Mitsudo Kenji , Shigetomi Toshio , Ueda Minoru , Ishigaki Takeo 
Published: April 2003

<i>Objective:</i> The purpose of this study was to evaluate the clinical efficacy, histopathological efficacy, and response to preoperative thermochemoradiotherapy for N<sub>3</sub> cervical lymph node metastases of oral cancer. <i>Methods:</i> Preoperative thermochemoradiotherapy was performed in 8 patients with oral cancer and N<sub>3</sub> cervical lymph node metastasis. These patients underwent four-weekly sessions of hyperthermia, combined with radiotherapy (40 Gy) as well as chemotherapy with cisplatin (CDDP; 100 mg/m<sup>2</sup>), all prior to surgery. Radical neck dissection was performed 4 weeks after completion of preoperative thermochemoradiotherapy. <i>Results:</i> The preoperative treatment of cervical lymph node metastases yielded a partial response in 6 patients, while 2 patients demonstrated no change. Histopathologically, grade III was detected in 1, grade IIb in 4 and grade IIa in 3 patients after surgery, according to the criteria of Shimosato. The follow-up period ranged from 13 to 64 months (mean 34). Of the 8 patients, 2 died (1 of lymph node metastasis and 1 had metastasis to a distant site), and 6 patients were alive at the last follow-up, with the longest postoperative disease-free survival being 63 months. The 5-year cumulative survival rate was 70.0%. <i>Conclusion:</i> These results indicate that preoperative thermochemoradiotherapy is a promising modality for patients with N<sub>3</sub> cervical lymph node metastasis of oral cancer.
Comparison of the Effectiveness of Scanning Laser Polarimetry and Optical Coherence Tomography for Estimating Optic Nerve Fibre Layer Thickness in Patients with Glaucoma
Authors: Furuichi Mieko , Kashiwagi Kenji , Furuichi Yoshiharu , Tsukahara Shigeo 
Published: April 2003

<i>Purpose:</i> The effectiveness of scanning laser polarimetry (by the nerve fibre analyser, NFA) and of optical coherence tomography (OCT) in estimating nerve fibre layer thickness (NFLT) and the correlations between NFLT and cup-to-disc (C/D) ratio or values of mean deviation (MD) from static visual field tests were compared using patients with glaucoma. <i>Materials and Methods:</i> Twenty-four eyes from 24 glaucoma patients were enrolled. The NFLT was measured along a circle with a diameter 1.5 times that of the optic disc around the optic disc. The averaged estimated NFLT of the circle or of each quadrantal NFLT (nasal, temporal, superior, inferior) was compared. <i>Results:</i> The co-variant indexes measured by the NFA were significantly smaller than those measured by OCT in both the averaged NFLT (p = 0.0002) and in each quadrantal NFLT (p < 0.05). The C/D ratio was significantly correlated with the averaged NFLT when measured by OCT (r = 0.425, p = 0.038), but not by the NFA (r = 0.179, p = 0.407). However, when measured by OCT, these values showed a significant correlation (r = 0.425, p = 0.039). Although both the OCT and NFA data showed significant correlations between NFLT and the MD (p = 0.0002 and p = 0.038, respectively), the OCT data showed a stronger correlation than did the NFA data (r = 0.677 and r = 0.422, respectively). The correlation between the averaged NFLTs obtained by NFA and OCT was not significant (r = 0.289, p = 0.172). <i>Conclusion:</i> OCT is thought to have an equal or better effectiveness for estimating NFLT, in spite of a lower reproducibility than that of the NFA.
Effects of Exogenous Surfactant and Recombinant Human Copper-Zinc Superoxide Dismutase on Oxygen-Dependent Antimicrobial Defenses
Authors: Walti Hervé , Nicolas-Robin Armelle , Assous Marc V. , Polla Barbara S. , Bachelet Maria , Davis Jonathan M. 
Published: April 2003

The use of human recombinant CuZn superoxide dismutase (rhSOD) in addition to exogenous surfactant has been studied as a therapeutic strategy to prevent acute and chronic lung injury in premature infants with blood monocytes (MO). However, scavenging of superoxide by rhSOD may compromise bacterial killing by phagocytes. In the present study, we investigated the interaction of exogenous surfactant and rhSOD with the antibacterial activity of human blood MO. MO were preincubated in the presence or absence of: (1) modified natural surfactant (Curosurf<sup>®</sup>; 1 mg/ml); (2) rhSOD (2,500 U/ml) and (3) bovine catalase (25,000 U/ml). Bacteria (<i>Legionella pneumophila </i>or <i>Escherichia coli</i>) were then added and incubated for 6 h. Viable bacteria were determined by counting colony-forming units. The ability of the MO to generate superoxide anions (O<sup>–</sup><sub>2</sub>) in response to bacterial infection was also investigated. The antibacterial capacity of MO was not impaired by the presence of rhSOD either alone or combined with Curosurf<sup>®</sup>. In some instances, bactericidal activity was even potentiated by the addition of rhSOD. Exposure of MO to catalase interfered with the increased bacterial killing of MO and rhSOD, suggesting that hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) production was critically important in the process of bacterial killing. Both bacterial species were also found to induce the generation of intra- and extracellular O<sup>–</sup><sub>2</sub> by MO. Data indicate that rhSOD potentiates the killing of bacteria by human MO. The mechanism of action appears to be related to the ability of bacteria to induce the generation of O<sup>–</sup><sub>2</sub>, which in turn is converted to H<sub>2</sub>O<sub>2</sub> in the presence of rhSOD. This has important implications in the development of therapeutic intervention strategies using antioxidant therapy in premature infants with respiratory distress syndrome.