bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vacuolar cytoplasmic phase separation in cultured mammalian cells involves the microfilament network and reduces motional properties of intracellular water
Authors: HENICS TAMÁS , WHEATLEY DENYS N. 
Published: November 2003

Hep‐2, human epithelial carcinoma cells, and human foreskin fibroblasts (FF9 and FF13) were exposed to either an ultrafiltrate (< 50 kD) of human sera or the weak base, procaine hydrochloride, to induce reversible cytoplasmic vacuolization. The formation of vacuoles was shown not to be due to imbibition of medium. Ultrastructural details obtained from various stages of vacuole formation were compared. In both cases of induction vacuoles were irregular and often appeared membraneless, with little in the way of electron‐dense content. They started to form in the perinuclear cytoplasm and progressed towards the periphery. Osmotic stress was not involved since mitochondria remained normal throughout a vacuolization episode.Vacuoles were often seen in close contact with filamentous structures, and this association remained detectable at late stages of the phenomenon. Fluorescent visualization of F‐actin confirmed that the vacuoles were frequently bordered by microfilaments. No major metabolic impairment was apparent in vacuolized cells as judged by protein synthesis measurements, but nuclear fluorescence (DNA content) and forward light scatter (nuclear volume) by flow cytometric analysis suggested late S phase and G2 retardation. 1H‐nmr relaxation measurements indicated intracellular water restricted in motional characteristics in vacuolized cells. The possibility of a restricted cytoplasmic phase separation as part of a transient adaptation response is raised, and a hypothesis to explain the findings is discussed.
Liver stem cells: when the going gets tough they get going
Authors: ALISON MALCOLM R. , GOLDING MATTHEW , SARRAF CATHERINE E. 
Published: November 2003

The ability of the liver to regenerate is widely acknowledged, and this is usually accomplished by the entry of normally proliferatively quiescent hepatocytes into the cell cycle. However, when hepatocyte regeneration is impaired, small bile ducts proliferate and invade into the adjacent hepatocyte parenchyma. In humans and experimental animals these ductal cells are referred to as oval cells, and their association with defective regeneration has led to the belief that they are the progeny of facultative stem cells. Oval cells are of great biological interest since they may represent a target population for hepatic carcinogens, and they may also be useful vehicles for ex vivo gene therapy for the correction of inborn errors of metabolism.The ability of oval cells to differentiate into hepatocytes has been demonstrated unequivocally. However, this process only occurs when the regenerative capacity of hepatocytes is overwhelmed, and thus, unlike the intestinal epithelium, the liver is not behaving as a classical continually renewing stem cell‐fed lineage.
Influence of chemical additives on the stability of dried tomato powder
Authors: Baloch Waqar A. , Khan Saifullah , Baloch Ahmad K. 
Published: November 2003

The effect of tomato slices being dipped in 1% (w/v) calcium chloride (CaCl2), 2% potassium metabisulphite or 2% sodium chloride (NaCl) solutions before oven‐drying on the carotenoid loss and browning development in the dry powder stored in air at 40°C for up to 90 d were tested. CaCl2 greatly increased carotenoid loss after 30 d until it was almost complete at 90 d, whereas metabisulphite decreased losses over most of the storage, only approaching the untreated values at the end. NaCl had no effect on carotenoid loss.Conversely, CaCl2 almost completely suppressed browning, whereas metabisulphite and NaCl had little or no effect on the rate of browning, but did reduce initial browning during drying. The untreated powder exceeded the shelf‐life criteria by the end of drying to about 12% moisture content.
Effects of noise stress on EFS‐mediated cholinergic and inhibitory NANC responses in tracheae from normal and sensitized guinea‐pigs
Authors: Breschi M.C. , Nieri P. , Lazzeri N. , Martinotti E. 
Published: November 2003

1 The aim of the present research was to study the cholinergic and inhibitory non‐adrenergic‐non‐cholinergic (NANC) responses obtained with electrical field stimulation (EFS) of tracheal tissues from sham‐ and noise‐exposed guinea‐pigs. A comparison was also made between normal and ovalbumin (OA)‐sensitized animals. 2 In proximal tracheae pretreated with indomethacin (3 μM), propranolol (1 μM), α‐chymotrypsin (2 U ml−1) and L‐NAME (0.1 mM), frequency‐dependent responses to EFS (0.1 ms width; 20 V, 0.1‐‐100 Hz, 15 s train duration) were obtained, both contractile and relaxing in nature. The contractile responses were abolished by atropine (1 μM), and did not vary significantly between sham‐ and noise‐exposed guinea‐pigs, or between normal and sensitized animals. The NANC relaxing responses, present in spite of the pre‐treatment of the tissues with L‐NAME and α‐chymotrypsin, and almost completely abolished by tetrodotoxin (TTX) treatment (10 μM), appeared to be enhanced in noise‐exposed guinea‐pigs, with respect to sham‐exposed animals, but only when the animals were not OA‐sensitized. 3 In distal tracheae contracted with histamine (10 μM), the study of the whole inhibitory NANC response (pre‐treatment with propranolol, but not with α‐chymotrypsin and L‐NAME), which was mainly TTX‐sensitive, revealed a statistically non‐significant difference between sham‐ and noise‐exposed guinea‐pigs, both normal and OA‐sensitized. When distal tracheae were preincubated with α‐chymotrypsin (2 U ml−1) and L‐NAME (0.1 mM), in addition to propranolol, a significant residual inhibitory NANC response to EFS was observed. Surprisingly, in this case, similarly to the evidence obtained in proximal tracheae, a significantly enhanced response was revealed in noise‐exposed guinea‐pigs with respect to sham‐exposed animals. 4 The noise‐induced enhancement of the relaxant response disappeared when the tissues were pretreated with the A2 purinergic antagonist 3,7‐dimethyl‐1‐propargylxanthine (DMPX, 1 μM), while it persisted in the presence of the A1 antagonist 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX, 10 nM). 5 The above data indicate that, while not modifying the cholinergic and the whole inhibitory NANC response to EFS, noise stress selectively influences an inhibitory component of the NANC system in guinea‐pig trachea with a mechanism probably involving an enhanced neurally mediated release of adenosine, which relaxes the smooth muscle via A2 receptors. This effect appears to be lacking or masked in sensitized guinea‐pigs.
Acetylcholinesterase histochemistry and functional characterization of the muscarinic receptor mediating the contraction of the bovine oesophageal groove
Authors: Barahona M. V. , Sánchez‐Fortún S. , San Andrés M. D. , Ballesteros E. , San Andrés M. 
Published: November 2003

1 By using acetylcholinesterase (AChE) histochemistry and invitro isometric techniques, we have studied the presence and distribution of AChE‐positive nerves, as well as the effects of muscarinic cholinoceptor agonists and selective antagonists, in the bovine oesophageal groove. 2 AChE‐positive nerves and cells were distributed widely on the oesophageal groove floor. These fibres originated from adventitial ganglia containing bodies with high AChE activity and were shown grouped as large adventitial nerve bundles. 3 Both in the presence and absence of physostigmine, acetylcholine (ACh) induced concentration dependent contractions of bovine oesophageal groove strips. The rank order of the pD2 values for muscarinic agonists was: oxotremorine‐M (7.37) = carbachol (7.14) > acetylcholine plus physostigmine (6.46) > bethanechol (5.42) > McN‐A‐343 (4.45) > acetylcholine (4.06). 4 Hexamethonium (10−6–10−4M), a nicotinic receptor blocker, did not affect the carbachol concentration–response curve, which was significantly inhibited by the muscarinic antagonist, atropine (10−9–10−8M). 5 The preferential muscarinic antagonists pirenzepine (M1), 11‐(2(‐(diethyl‐amino)methyl)‐1‐piperidinylacetyl)‐5,‐11‐dihydro‐6H‐pyrido(2,3‐b)‐(1,4)‐benzodiazepine‐6‐one (AF‐DX 116) and methoctramine (M2), 4‐diphenyl‐acetoxy‐N‐methyl‐piperidine methiodide (4‐DAMP) and p‐fluoro‐hexahydrosiladiphenidol (p‐F‐HHSiD) (M3) and tropicamide (M4) evoked rightwards displacements in a parallel manner of the carbachol control curve, and there was no decrease of the maximum response with the highest concentration of antagonist utilized. The muscarinic antagonist affinities, expressed in terms of pA2 values, were: atropine (9.51) = 4‐DAMP (9.32) > p‐F‐HHSiD (7.78) > tropicamide (7.40) > pirenzepine (6.91) = AF‐DX 116 (6.88) = methoctramine (6.71). This muscarinic antagonist profile suggests that an M3 receptor is involved in the carbachol induced contraction. 6 The present results suggest that a rich network of AChE‐ positive fibres is present in the oesophageal groove floor, where they form a nerve trunk and thinner branches accompanying blood vessels and sometimes around ganglia. The muscarinic cholinergic contraction of the bovine oesohageal groove seems to be mediated via activation of an M3 postsynaptic muscarinic receptor.
The peripheral NK‐1/NK‐2 receptor antagonist MDL 105,172A inhibits tachykinin‐mediated respiratory effects in guinea‐pigs
Authors: Kudlacz E.M. , Knippenberg R.W. , Shatzer S.A. , Kehne J.H. , McCloskey T.C. , Burkholder T.P. 
Published: November 2003

1 Stimulation of sensory nerves causes release of tachykinins, including substance P (SP) and neurokinin A (NKA), which produce a variety of respiratory effects via NK‐1 and NK‐2 receptors, respectively. Hence, development of a compound which could potently and equivalently antagonize both receptors was pursued. 2 MDL 105,172A ((R)‐1‐[3‐(3,4‐dichlorophenyl)‐1‐(3,4,5‐trimethoxybenzoyl)‐3‐pyrrolidinyl]‐4‐phenyl‐piperidine‐4‐morpholinecarboxamide) exhibited high affinity for NK‐1 (4.34 nm) and NK‐2 (2.05 nm) receptors. In vitro, the compound antagonized SP (pA2 = 8.36) or NKA (pA2 = 8.61)‐induced inositol phosphate accumulation in tachykinin monoreceptor cell lines. 3 In anaesthetized guinea‐pigs, MDL 105,172A inhibited SP‐induced plasma protein extravasation (ED50 = 1 mg kg−1, i.v.) and [β‐Ala8]NKA 4–10‐induced bronchoconstriction (ED50 = 0.5 mg kg−1, i.v.) indicating NK‐1 and NK‐2 antagonism, respectively. 4 Capsaicin was used to elicit respiratory effects in anaesthetized and conscious guinea‐pigs; the latter were inhibited by MDL 105,172A following i.v. (ED50 = 1 mg kg−1) or oral (ED50 = 20 mg kg−1) adminstration. Hence, MDL 105,172A can inhibit pulmonary responses to tachykinins released endogenously in the airways. 5 At doses up to 200 mg kg−1, p.o., MDL 105,172A failed to inhibit repetitive hind paw tapping induced by i.c.v. GR 73632, an NK‐1 selective agonist, in gerbils, whereas CP‐99,994 (0.87 mg kg−1, s.c.) completely ablated the effect. These data suggest that MDL 105,172A does not penetrate the central nervous system (CNS) and its tachykinin antagonism is restricted to the periphery. 6 MDL 105,172A is a non‐peptide, potent, equivalent antagonist of NK‐1 and NK‐2 receptors. Its ability to inhibit both exogenously administered as well as endogenously released tachykinins support its use in examining the role of sensory neuropeptides in diseases associated with neurogenic inflammation including asthma.
Vasoconstriction of rat renal interlobar arteries by noradrenaline and neuropeptide Y
Authors: Chen H. , Bischoff A. , Schäfers R. F. , Wambach G. , Philipp T. , Michel M. C. 
Published: November 2003

1 We have studied the contractile effects of noradrenaline and neuropeptide Y given alone and in combination on isolated rat renal interlobar arteries. 2 Noradrenaline contracted proximal and distal intrarenal microvessels in a concentration dependent manner, with similar potency (EC50≈ 550 nM), but maximum effects were greater in the proximal than in the distal vessel segments (≈ 10 and 6 mN, respectively). 3 The noradrenaline‐induced contraction was inhibited by low prazosin concentrations (3‐‐10 nM) but not by 1 μM yohimbine indicating involvement of α1‐ but not α2‐adrenoceptors. The α1A‐adrenoceptor‐selective antagonists, 5‐methylurapidil and tamsulosin, had high potency (apparent affinities of ≈ 8 nM and 57 pM, respectively) while the α1D‐adrenoceptor‐selective antagonist, BMY 7378, had only low potency (apparent affinity ≈ 300 nM). The α1B‐adrenoceptor‐alkylating agent, chloroethylclonidine (10 μM for 30 min at 37°C), had no inhibitory effects. The Ca2+ entry blocker, nitrendipine (300 nM), reduced the potency and maximal effects of noradrenaline. 4 Neuropeptide Y (1‐‐100 nM) also contracted interlobar arteries in a concentration dependent manner, with greater effects in the proximal than in the distal segments, but maximal effects were only small in either segment (<2 mN). In addition, neuropeptide Y also potentiated the response to noradrenaline, i.e. lowered its EC50 but this enhancement was also small. 5 We conclude that noradrenaline contracts rat interlobar arteries by an α1A‐adrenoceptor; its co‐transmitter, neuropeptide Y, affects the response only marginally in this vascular bed.
Effects of esmolol on 35 GHz microwave‐induced lethal heat stress
Authors: Jauchem J. R. , Ryan K. L. , Lovelace J. D. , Frei M. R. 
Published: November 2003

1 The purpose of this study was to examine effects of the β1‐adrenoreceptor antagonist esmolol (infused at 2 or 4 mg kg−1 body wt min−1) on heart rate, blood pressure, respiratory rate, localized body temperature changes, survival times, and lethal body temperatures that occur during the exposure of anesthaetized rats to 35 GHz microwaves. 2 Forty Sprague–Dawley rats, anaesthetized with ketamine, were exposed to 35 GHz microwaves at a level that resulted in heating and death. During irradiation, a continuous increase in heart rate and a biphasic response in blood pressure (initial increase followed by a decrease) were observed in all groups of animals. 3 Esmolol caused a significant dose‐dependent decrease in blood pressure, relative to saline‐treated animals, but only a small attenuation of the heat‐induced rise in heart rate. In experiments in which esmolol was infused and microwave exposure was continued until death, drug‐treated animals survived for significantly shorter periods and died at significantly lower body temperatures. The change in survival may have been related to the lower blood pressure due to esmolol treatment.
The effects of bromoacetylalprenololmenthane on the responses to isoprenaline of the left ventricle from normo‐, prehyper‐ and hypertensive rats
Authors: Doggrell S. A. , Mistry D. N. , Henderson C. J. 
Published: November 2003

1 We have studied the effects of bromoacetylalprenololmenthane (BAAM), a very slowly reversible β‐adrenoceptor antagonist, on the responses of the left ventricle of 5 and 22 week old Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) to isoprenaline. At 5 weeks the SHRs were prehypertensive and at 22 weeks they had hypertension‐induced hypertrophy of the left ventricle. 2 The mean potency of isoprenaline on the left ventricle from 5 week old WKY was similar to that obtained on left ventricles from 22 week old WKY, and 5 and 22 week old SHRs. 3 Following treatment of the left ventricle with BAAM at 10−6m for 30 min, there was a parallel rightward shift of the isoprenaline concentration–response curves. Treatment with a higher concentration of BAAM (10−5m) caused non‐parallel rightward shifts of the concentration–response curves, with a depression of the isoprenaline maximum responses. These data were used to derive affinity (KA) values for isoprenaline. The mean isoprenaline KA value on the left ventricle from 5 week old WKY was 2.44 × 10−6m, and similar KA values were obtained on the left ventricles from 22 week old WKY and 5 and 22 week old SHRs. On all the left ventricles tested, isoprenaline produced a half maximal response by occupying less than 1%, and a near maximal response by occupying about 5% of the available β1‐adrenoceptors. 4 This study has shown that there are no differences in the cardiac responses to isoprenaline at β1‐adrenoceptors, isoprenaline KA values or the β1‐adrenoceptor reserve for isoprenaline on the SHR left ventricle in prehypertension or in the early stages of hypertension‐induced hypertrophy.
Chronic terbutaline treatment desensitizes β‐adrenergic inhibition of lymphocyte activation in healthy volunteers
Authors: Werner C. , Poller U. , Brodde O.‐E. 
Published: November 2003

1 A substantial body of evidence has accumulated that β‐adrenoceptor mediated increases in human lymphocyte cyclic AMP can inhibit activation of resting lymphocytes. The aim of this study was to determine whether this effect might desensitize during chronic β‐adrenoceptor agonist treatment. We assessed the effects of 2 weeks treatment with the β2‐adrenoceptor agonist terbutaline (3 × 5 mg day−1 p.o.) on isoprenaline‐induced inhibition of concanavalin A‐evoked lymphocyte activation in nine healthy male volunteers. Lymphocyte activation was determined by [3H]‐thymidine incorporation (as a measure of proliferation), and inositol phosphate formation was assessed in [3H]‐myo‐inositol prelabelled lymphocytes in the presence of 10 mm LiCl. 2 Terbutaline treatment caused a significant reduction in isoprenaline (1 nm– 10 μm)‐induced increases in lymphocyte cyclic AMP content; the maximal increase was 14 ± 3 pmol/106 cells before and 7 ± 2 pmol/106 cells (n= 9, P < 0.05) after terbutaline treatment. 3 The mitogen concanavalin A (Con A, 1–32 μg ml−1)‐induced increase in inositol phosphate formation was significantly enhanced after terbutaline treatment (max. increase before treatment: 255 ± 25% above basal; after treatment 453 ± 16% above basal; n= 9, P < 0.001), while isoprenaline (1 nm– 10 μm)‐induced inhibition of Con A (16 μg ml−1)‐evoked increases in inositol phosphate formation was significantly reduced after the terbutaline treatment (max. inhibition before treatment: 22 ± 4%; after treatment 9 ± 1%, n= 9, P < 0.01). 4 Con A (1.25 – 10 μg ml−1)‐induced increases in [3H]‐thymidine incorporation into the lymphocytes (as a measure of proliferation) was not affected by the terbutaline treatment. On the other hand, isoprenaline (1 nm– 1 μm)‐induced inhibition of Con A (5 μg ml−1)‐evoked lymphocyte proliferation (max. inhibition: 33 ± 7%, n= 9) was almost completely abolished after the terbutaline treatment. 5 We conclude that chronic treatment with terbutaline desensitizes lymphocyte β2‐adrenoceptors and, therefore, the inhibitory effect of cyclic AMP on lymphocyte activation.
‘Best clinical practice’: assessment of processes of care and of outcomes in the US Military Health Services System
Authors: Krakauer Henry , Lin Monica Jia‐Yeong , Schone Eric M. , Park Dae , Miller Richard C. , Greenwald Jeffrey , Bailey R. Clifton , Rogers Barbara , Bernstein Geoffrey , Lilienfeld David E. , Stahl Sidney M. , Crawford Raymond S. , Schutt David C. 
Published: November 2003

The National Quality Management Program of the Military Health Services System of the United States has undertaken a series of projects whose objective is the active, on‐going monitoring and improvement of the effectiveness and efficiency of the care provided to a broad population that encompasses troops on active duty, retirees and dependents. The analytic activities consist of (1) identification by clinical panels of conditions and procedures of interest; (2) collection of data from electronic repositories and from charts to characterize the patients, how they are managed, the clinical outcomes they experience, the resource costs their care entails, and, from questionnaires, their functional status and level of satisfaction, and (3) generation of ‘report cards’ that inform organizational units down to the level of the hospital of the characteristics of their patients, their practices, and the risk‐adjusted outcomes they achieve. The patterns of care employed by the hospitals that obtain the best risk‐adjusted outcomes and resource utilization (‘best clinical practice’) are identified and made known. In addition, (4) a systematic process of developing outcomes‐based practice guidelines has been devised. Its intent is to serve as a decision‐support tool for clinicians. Initial estimates have been obtained of the probable consequences of the application of this tool to operative interventions in childbirth. Use of the tool would result in a higher occurrence of elective Caesarean sections, a reduced rate of emergency Caesarean sections and much lower use of forceps, with an overall improvement in outcomes and lower resource costs.This program is currently in the early phases of implementation. The two principal requirements for the immediate future are (1) education of the clinical and administrative communities in the use of the data and the decision‐support tools and (2) evaluation of the consequences of the use of the data by the clinical and administrative communities.
In the queue for total joint replacement: patients' perspectives on waiting times
Authors: Llewellyn‐Thomas Hilary A. , Arshinoff Rena , Bell Mary , Williams J. Ivan , Naylor C. David 
Published: November 2003

We assessed patients on the waiting lists of a purposive sample of orthopaedic surgeons in Ontario, Canada, to determine patients' attitudes towards time waiting for hip or knee replacement. We focused on 148 patients who did not have a definite operative date, obtaining complete information on 124 (84%). Symptom severity was assessed with the Western Ontario/McMaster Osteoarthritis Index and a disease‐specific standard gamble was used to elicit patients' overall utility for their arthritic state. Next, in a trade‐off task, patients considered a hypothetical choice between a 1‐month wait for a surgeon who could provide a 2% risk of post‐operative mortality, or a 6‐month wait for joint replacement with a 1% risk of post‐operative mortality. Waiting times were then shifted systematically until the patient abandoned his/her initial choice, generating a conditional maximal acceptable wait time.Patients were divided in their attitudes, with 57% initially choosing a 6‐month wait with a 1% mortality risk. The overall distribution of conditional maximum acceptable wait time scores ranged from 1 to 26 months, with a median of 7 months. Utility values were independently but weakly associated with patients' tolerance of waiting times (adjusted R‐square = 0.059, P= 0.004). After splitting the sample along the median into subgroups with a relatively ‘low’ and ‘high’ tolerance for waiting, the subgroup with the apparently lower tolerance for waiting reported lower utility scores (z= 2.951; P= 0.004) and shorter times since their surgeon first advised them of the need for surgery (z= 3.014; P= 0.003).These results suggest that, in the establishment and monitoring of a queue management system for quality‐of‐life‐enhancing surgery, patients' own perceptions of their overall symptomatic burden and ability to tolerate delayed relief should be considered along with information derived from clinical judgements and pre‐weighted health status instruments.
A morphological study off a thyroid carcinoma in a medaka, Oryzias latipes (Temminck & Schlegel)
Authors: Harada T , Itoh H , Hatanaka J , Kamiya S , Enomoto M 
Published: November 2003

AbstractA large mass protruding beyond the left operculum was found in an adult male medaka, Oryzias latipes (Temminck & Schlegel). Histologically, the mass was mainly composed of thyroid follicles measuring up to 292 μm in diameter. The follicular epithelium consisted of cuboidal or squamous cells. The follicles lacked colloidal material in the lumen. The thyroid tissue infiltrated into the kidney. Electron microscopically, the tumour cells were characterized by dilation and vesiculation of rough endoplasmic reticulum, which extended throughout the cytoplasm, and an irregular outline of the nucleus. Mitotic figures and partly degenerate cells were frequently observed. Based on the above features, the tumour was diagnosed as a follicular carcinoma of the thyroid, the first reported case in the medaka.