bluuebunny/crossref_metadata_2025_split huggingface dataset:
K+ transport in Malpighian tubules of Tenebrio molitor L.: is a KATP channel involved?
Authors: Wiehart U. I. M. , Klein G. , Steels P. , Nicolson S. W. , Van Kerkhove E. 
Published: February 2003

SUMMARY
The presence of ATP-regulated K+ (KATP) channels in Tenebrio molitor Malpighian tubules was investigated by examining the effect of glibenclamide on both fluid secretion and basolateral membrane potentials (Vbl). Glibenclamide, a KATP channel blocker, slowed fluid secretion of Tenebrio tubules. In low bath K+ concentration (5 mmol l-1), glibenclamide either hyperpolarized or depolarized Vbl, resembling the effect seen with Ba2+. Subsequent addition of 6 mmol l-1Ba2+ caused a further hyper- or depolarization of Vbl. In control Ringer (50 mmol l-1 KCl, 90 mmol l-1 NaCl), glibenclamide had no visible effect on Vbl. The effect of ouabain was investigated in low bath[K+] in the presence of Ba2+. Vblresponded by a small but significant hyperpolarization from -51±4 mV to-56±4 mV (n=16, P&lt;0.001) in response to 1 mmol l-1 ouabain. Repeating the experiments in the presence of both glibenclamide and Ba2+ resulted in a depolarization of Vbl when ouabain was added. In low bath [K+](high Na+), the Na+/K+-ATPase is expected to function at a high rate. In the presence of Ba2+, replacing Na+ by K+ rapidly depolarized Vbl,but this was followed by a repolarization. Repeating the experiments in the presence of glibenclamide markedly reduced the depolarizing effect and abolished the repolarization, with a gradual decrease in the sensitivity of Vbl to the surrounding [K+]. These results suggest the presence of KATP channels in the basolateral membrane. Glibenclamide had no visible effect on Vbl in high K+ or in the absence of Ba2+, indicating that other highly conductive K+ channels may mask the effect on KATP channels. This is the first demonstration of the presence of KATP channels in an insect epithelium.
ATP‐induced calcium oscillations and change of P2Y subtypes with culture conditions in HeLa cells
Authors: Okuda Akico , Furuya Kishio , Kiyohara Toshikazu 
Published: February 2003

AbstractATP, UTP, ADP and UDP induced intracellular Ca2+ responses and oscillations in HeLa cells that sometimes lasted over 1 h. The response is due to the activation of P2Ys, G‐protein coupled ATP receptors, because the oscillations persisted for several minutes even in Ca2+‐free solution, and suramin and PPADS, antagonists of ATP receptors, partially inhibited the response. The potency of these nucleotides varied with the culture or cell conditions, i.e. UTP was generally most potent but in some cases UDP was more potent; responses to UDP were variable while those to ATP were constant. In addition, Ca2+ responses to ATP and UDP were additive. These findings suggested the existence of two or more subtypes of P2Ys in HeLa cells. RT‐PCR experiments revealed the existence of P2Y2, P2Y4 and P2Y6. Recovery from starvation (culture in FBS‐free medium overnight and re‐addition of FBS) increased the responses to UTP and UDP but not to ATP, suggesting that the number or activity of P2Y6 and/or P2Y4 receptors may increase with cell proliferation in HeLa cells. Copyright © 2002 John Wiley & Sons, Ltd.
Effects of steroid hormones on five functional parameters of Tetrahymena: evolutionary conclusions
Authors: Kőhidai László , Katona Júlia , Csaba György 
Published: February 2003

AbstractThe unicellular Tetrahymena pyriformis was studied for chemotaxis, chemotactic selection, phagocytosis, growth and body shape changes in the presence of water soluble (β‐cyclodextrin‐coupled) steroid hormones (testosterone, estradiol, progesterone, hydrocortisone and dexamethasone). Testosterone was chemoattractant over a wide range of concentrations, while progesterone and dexamethasone were active only at one concentration (10−5 and 10−6 mg ml−1 respectively) and were either neutral or repellent at other concentrations. Hydrocortisone and estradiol were unambiguously chemorepellent. Chemotactic selection enhanced the effect of testosterone and estradiol, while in the case of hydrocortisone the action was reversed. The other parameters were mildly influenced by the steroid hormones. The results call attention to the fine molecular recognition capacity of Tetrahymena and to the possible rapid effects of steroid hormones at membrane receptors at a very low evolutionary eukaryotic level. Copyright © 2002 John Wiley & Sons, Ltd.
Improvement of the biocompatibility of alginate/poly‐L‐lysine/alginate microcapsules by the use of epimerized alginate as a coating
Authors: King Aileen , Strand Berit , Rokstad Anne‐Mari , Kulseng Bård , Andersson Arne , Skjåk‐Bræk Gudmund , Sandler Stellan 
Published: February 2003

AbstractAlginate/poly‐L‐lysine(PLL)/alginate capsules are used widely for the microencapsulation of cells. Alginate consists of guluronic acid and mannuronic acid, the ratio and sequence of which affect the properties of the alginate. Using C5‐epimerases, mannuronic acid can be converted to guluronic acid in the alginate polymer. Such an enzyme, AlgE4, was used to convert blocks of mannuronic acid (M‐blocks) to blocks of alternating sequence (MG‐blocks). The aims of this study were 1) to investigate whether the use of epimerized alginate as a coating could improve the biocompatibility of alginate/PLL/alginate capsules and 2) to study the biocompatibility of simple alginate beads prepared with epimerized alginate. Four different capsules, two of which contained epimerized alginate, were investigated after implantation in C57BL/6 mice for 1 week. The biocompatibility of alginate/PLL/alginate capsules, as measured by retrieval rates of the capsules and DNA contents and glucose oxidation rates of the cellular overgrowth, was improved when an epimerized coating alginate was used. There were, however, no statistically significant differences in the biocompatibility of simple alginate beads made from epimerized alginate when compared with non‐epimerized alginate beads. In general, such beads produced without a PLL coating swelled to a higher extent than the conventional alginate/PLL/alginate capsules. In conclusion, the use of an epimerized coating on alginate‐PLL‐alginate can improve the biocompatibility of such capsules but still cannot completely eliminate the detrimental effects of PLL on the biocompatibility of the capsules. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 533–539, 2003
Controlled release of fibroblast growth factors and heparin from photocrosslinked chitosan hydrogels and subsequent effect on in vivo vascularization
Authors: Ishihara Masayuki , Obara Kiyohaya , Ishizuka Toshiaki , Fujita Masanori , Sato Masato , Masuoka Kazunori , Saito Yoshio , Yura Hirofumi , Matsui Takemi , Hattori Hidemi , Kikuchi Makoto , Kurita Akira 
Published: February 2003

AbstractApplication of ultraviolet (UV) irradiation to a photocrosslinkable chitosan (Az‐CH‐LA) aqueous solution resulted within 10 s in an insoluble, flexible hydrogel. A low molecular weight acidic molecule like trypan blue and various high molecular weight molecules such as bovine serum albumin (BSA), heparin and protamine were all retained within the hydrogel, while a low molecular weight basic molecule like toluidine blue was rapidly released from the hydrogel. In the present work, we examined the retaining capability of the chitosan hydrogel for growth factors and controlled release of growth factors from the chitosan hydrogel in vitro and in vivo. Fibroblast growth factor‐1 (FGF‐1), fibroblast growth factor‐2 (FGF‐2), vascular endothelial growth factor165 (VEGF165), heparin‐binding epidermal growth factor (HB‐EGF) in phosphate buffered saline (PBS) were mixed with Az‐CH‐LA aqueous solution to form growth factor‐incorporated chitosan hydrogels. About 10–25% of the growth factor was released from a growth factor‐incorporated chitosan hydrogel into PBS within the first day, after which no further substantial release took place. The growth factors interacted with Az‐CH‐LA molecules poly‐ion complexation, and probably were unable to be released after the first day under the in vitro nondegradation conditions of the hydrogel. Although the FGF‐1, FGF‐2, and VEGF165‐incorporated chitosan hydrogels on a culture plate significantly stimulated HUVEC growth, the stimulating activity of the growth factor‐incorporated chitosan hydrogel was completely cancelled out by washing the hydrogel with PBS solution for 3 days or more. The stimulating activity on the HUVEC growth were however highly recovered by treating the washed growth factor‐incorporated chitosan hydrogel during 7 days with chitinase and chitosanase to partly degrade the hydrogel, strongly suggesting that the growth factors within the hydrogel retained their biologically active forms. The chitosan hydrogel (100 μl) when implanted into the back of a mouse was biodegraded in about 10–14 days. When FGF‐1‐ and FGF‐2‐incorporated chitosan hydrogels were subcutaneously implanted into the back of a mouse, significant neovascularization was induced near the implanted site of the FGF‐1‐ and FGF‐2‐incorporated chitosan hydrogels. Furthermore, addition of heparin with either FGF‐1 or FGF‐2 into the hydrogel resulted in a significantly enhanced and prolonged vascularization effect. These results indicate that the controlled release of biologically active FGF‐1 and FGF‐2 with heparin is caused by biodegradation of the chitosan hydrogel, and subsequent induction of vascularization. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 551–559, 2003
Supraspinal N‐methyl‐D‐aspartate receptor inhibition influences the micturition reflex and function of the upper urinary tract of anesthetized and conscious rats
Authors: Tillig Bernd , Constantinou Christos E. 
Published: February 2003

AbstractAimsTo examine the effects of N‐methyl‐D‐aspartate (NMDA) receptor antagonists on the frequency/volume (F/V) characteristics of micturition of conscious and anesthetized rats in relation to the mechanisms of renal urine output and pyelo‐ureteral transport function of the upper urinary tract.MethodsMicturition F/V characteristics of 24 conscious female Sprague‐Dawley rats, each weighting 160–180 g, were evaluated in a metabolic chamber. Control values of (F/V) were first obtained after administration of a 5‐mL loading dose of saline solution and compared with intraperitoneal (i.p.) injection of 0.3–6.0 mg/kg of LY274614 (LY) and 0.3–40 mg/kg of dextromethorphan (DEX). Upper urinary tract studies were performed on two groups of urethane anesthetized rats (1.2 g/kg, s.c.). A group of 17 rats was used for intravenous (i.v.) injection of 1–30 mg/kg of LY and 1–10 mg/kg of DEX. In a second group of 12 rats, 0.2 mg/kg of LY and DEX were administered intracerebroventricularly (i.c.v.), by placing a catheter into the third ventricle. In anesthetized rats, continuous cystometrograms (CMG) were done while perfusing the renal pelvis with indigo carmine, and measuring pelvic and arterial pressure and as well as visualizing the transport of urine within the upper urinary tract by using videomicroscopic imaging.ResultsIn conscious rats, the i.p. injection of LY and DEX produced a significant and dose‐dependent increase in functional bladder capacity and a considerable increase in diuresis. In anesthetized rats, i.v. and i.c.v. administration of LY and DEX affected the micturition reflex, reflected as a significant increase in bladder capacity and preleakage pressure. Videomicroscopic imaging shows dilation of the ureter and a dilution of the dyed urine after the i.v. and i.c.v. injection of LY and DEX. The frequency of ureteral peristalsis and renal pelvic contractions were significantly decreased after i.v. and i.c.v. injection of LY as well as DEX.ConclusionsThe present study shows that the NMDA receptor antagonists LY and DEX given systemically (i.v. and i.p.) or intracerebroventricularly influence the micturition reflex and modulate pyelo‐ureteral motility as well as the rate of urine production. From the present study, it is suggested that NMDA receptors are directly involved in regulating pyelo‐ureteral peristalsis as well as in the coordination of urine transport between upper and lower urinary tract. Neurourol. Urodynam. 22:164–175, 2003. © 2003 Wiley‐Liss, Inc.
Leydig cell micronodules are a common finding in testicular biopsies from men with impaired spermatogenesis and are associated with decreased testosterone/LH ratio
Authors: Holm Mette , Rajpert‐De Meyts Ewa , Andersson Anna‐Maria , Skakkebæk Niels E 
Published: February 2003

AbstractTo assess the biological significance of Leydig cell ‘hyperplasia’ in man, Leydig cell distribution, volume, and function were studied in patients with infertility or testicular cancer and in suddenly deceased controls. A total of 156 biopsies from 95 patients and 18 necropsies from 13 controls were examined using a semi‐quantitative stereological method. In patients, serum concentrations of testosterone, sex hormone binding globulin (SHBG), luteinizing hormone (LH), follicle stimulating hormone (FSH), oestradiol and inhibin‐B were correlated with the findings on histological examination. Leydig cell clusters of more than 15 cells in a cross‐section, for which we proposed the name ‘micronodules’, were frequently seen in testicles exhibiting Sertoli‐cell‐only syndrome (SCO), a mixed pattern of impaired spermatogenesis, or complete spermatogenesis in combination with elevated FSH. Median numbers of micronodules per 1.77 mm2 (four fields of vision) in these three histological patterns were 6, 4, and 3.5, respectively. In contrast, micronodules were only occasionally observed in testicular biopsies from patients with complete spermatogenesis and normal gonadotrophin levels (median 1), and were rare in testes from controls (median = 0, p = 0.02). The proportion of testicular tissue occupied by Leydig cells increased with decreasing spermatogenic capacity. In contrast, the total volume of Leydig cells per testis was roughly comparable irrespective of the histological pattern, with the exception of testes with bilateral micronodules, which had significantly increased Leydig cell volume compared to those without micronodules. The number of micronodules correlated positively to LH (r = 0.577, p < 0.01) and FSH (r = 0.595, p < 0.01) and the presence of micronodules was most pronounced in the hyperstimulated testes, as reflected by an increased LH/testosterone ratio. In conclusion, Leydig cell micronodules were more frequent in biopsies with impaired spermatogenesis and associated with decreased ratios of testicular hormones to gonadotrophins. The presence of micronodules thus seems to be a histological marker of testicular failure in man. Copyright © 2003 John Wiley & Sons, Ltd.
Integrating artificial intelligence into on‐line statistical process control
Authors: Guh Ruey‐Shiang 
Published: February 2003

AbstractStatistical process control (SPC) is one of the most effective tools of total quality management, the main function of which is to monitor and minimize process variations. Typically, SPC applications involve three major tasks in sequence: (1) monitoring the process, (2) diagnosing the deviated process and (3) taking corrective action. With the movement towards a computer integrated manufacturing environment, computer based applications need to be developed to implement the various SPC tasks automatically. However, the pertinent literature shows that nearly all the researches in this field have only focussed on the automation of monitoring the process. The remaining two tasks still need to be carried out by quality practitioners.This project aims to apply a hybrid artificial intelligence technique in building a real time SPC system, in which an artificial neural network based control chart monitoring sub‐system and an expert system based control chart alarm interpretation sub‐system are integrated for automatically implementing the SPC tasks comprehensively. This system was designed to provide the quality practitioner with three kinds of information related to the current status of the process: (1) status of the process (in‐control or out‐of‐control). If out‐of‐control, an alarm will be signaled, (2) plausible causes for the out‐of‐control situation and (3) effective actions against the out‐of‐control situation. An example is provided to demonstrate that hybrid intelligence can be usefully applied for solving the problems in a real time SPC system. Copyright © 2003 John Wiley & Sons, Ltd.
Hepatocellular carcinoma: Gardening strategies and bridges to transplantation
Authors: Gores Gregory J. 
Published: February 2003

Abstract

Background:
Survival after liver transplantation for early hepatocellular carcinoma (HCC) is worsened by the increasing dropout rate while waiting for a donor.

Aims:
To assess the cost effectiveness of adjuvant therapy while waiting for liver transplantation in HCC patients.

Method:
Using a Markov model, a hypothetical cohort of cirrhotic patients with early HCC was considered for: (1) adjuvant treatment-resection was limited to Child-Pugh’s A patients with single tumours, and percutaneous treatment was considered for Child-Pugh’s A and B patients with single tumours unsuitable for resection or with up to three nodules < 3 cm; and (2) standard management. Length of waiting time ranged from six to 24 months.

Results:
Surgical resection increased the transplantation rate (>10%) and provided gains in life expectancy of 4.8-6.1 months with an acceptable cost ($40,000/ year of life gained) for waiting lists > or = 1 year whereas it was not cost effective ($74,000/life of year gained) for shorter waiting times or high dropout rate scenarios. Percutaneous treatment increased life expectancy by 5.2-6.7 months with a marginal cost of approximately $20,000/year of life gained in all cases, remaining cost effective for all waiting times.

Conclusions:
Adjuvant therapies for HCC while waiting for liver transplantation provide moderate gains in life expectancy and are cost effective for waiting lists of one year or more. For shorter waiting times, only percutaneous treatment confers a relevant survival advantage.
Teriparatide has no effect on the calcium‐mediated pharmacodynamics of digoxin
Authors: Benson Charles T. , Voelker James R. 
Published: February 2003

BackgroundTeriparatide (recombinant human parathyroid hormone [1‐34]) stimulates bone formation and causes small transient increases in serum calcium concentration. We assessed whether teriparatide causes a change in digoxin pharmacodynamic effects by measuring systolic time intervals and heart rate.MethodsMeasurements were made by echocardiographic Doppler that examined 3 systolic time intervals, as follows: QS2 (time from Q wave on electrocardiogram to the closure of the aortic valve), left ventricular ejection time, and pre‐ejection period, all corrected for changes in heart rate. Fifteen healthy subjects (2 men and 13 women) were administered a single subcutaneous teriparatide dose (20 μg) on day 1 and then equilibrated on a daily oral dose of digoxin for 15 days. Subcutaneous placebo and teriparatide, 20 μg, were given in a randomized crossover design with the 14th (day 15) and 15th (day 16) digoxin doses. Serial systolic time interval and heart rate measurements were obtained on days 1, 15, and 16.ResultsAfter subjects were dosed to steady state with digoxin, there were statistically significant reductions in QS2 corrected for heart rate (QS2c) of 23 to 25 ms and heart rate of 4 to 6 beats/min. However, there was no difference between treatment with digoxin plus placebo versus digoxin plus teriparatide. The study was powered to find a difference in QS2c as small as 6 ms (α = .05, β = .2).Conclusion: Teriparatide, 20 μg subcutaneously, does not alter the cardiac effect of digoxin.Clinical Pharmacology & Therapeutics (2003) 73, 87–94; doi: 10.1067/mcp.2003.7
mRNAs Encoding Telomerase Components and Regulators Are Controlled by
UPF
Genes in
Saccharomyces cerevisiae
Authors: Dahlseid Jeffrey N. , Lew-Smith Jodi , Lelivelt Michael J. , Enomoto Shinichiro , Ford Amanda , Desruisseaux Michelle , McClellan Mark , Lue Neal , Culbertson Michael R. , Berman Judith 
Published: February 2003

ABSTRACT

Telomeres, the chromosome ends, are maintained by a balance of activities that erode and replace the terminal DNA sequences. Furthermore, telomere-proximal genes are often silenced in an epigenetic manner. In
Saccharomyces cerevisiae
, average telomere length and telomeric silencing are reduced by loss of function of
UPF
genes required in the nonsense-mediated mRNA decay (NMD) pathway. Because NMD controls the mRNA levels of several hundred wild-type genes, we tested the hypothesis that NMD affects the expression of genes important for telomere functions. In
upf
mutants, high-density oligonucleotide microarrays and Northern blots revealed that the levels of mRNAs were increased for genes encoding the telomerase catalytic subunit (Est2p), in vivo regulators of telomerase (Est1p, Est3p, Stn1p, and Ten1p), and proteins that affect telomeric chromatin structure (Sas2p and Orc5p). We investigated whether overexpressing these genes could mimic the telomere length and telomeric silencing phenotypes seen previously in
upf
mutant strains. Increased dosage of
STN1
, especially in combination with increased dosage of
TEN1
, resulted in reduced telomere length that was indistinguishable from that in
upf
mutants. Increased levels of
STN1
together with
EST2
resulted in reduced telomeric silencing like that of
upf
mutants. The half-life of
STN1
mRNA was not altered in
upf
mutant strains, suggesting that an NMD-controlled transcription factor regulates the levels of
STN1
mRNA. Together, these results suggest that NMD maintains the balance of gene products that control telomere length and telomeric silencing primarily by maintaining appropriate levels of
STN1
,
TEN1
, and
EST2
mRNA.
TOK Homologue in
Neurospora crassa
: First Cloning and Functional Characterization of an Ion Channel in a Filamentous Fungus
Authors: Roberts Stephen K. 
Published: February 2003

ABSTRACT

In contrast to animal and plant cells, very little is known of ion channel function in fungal physiology. The life cycle of most fungi depends on the “filamentous” polarized growth of hyphal cells; however, no ion channels have been cloned from filamentous fungi and comparatively few preliminary recordings of ion channel activity have been made. In an attempt to gain an insight into the role of ion channels in fungal hyphal physiology, a homolog of the yeast K
+
channel (ScTOK1) was cloned from the filamentous fungus,
Neurospora crassa
. The patch clamp technique was used to investigate the biophysical properties of the
N. crassa
K
+
channel (NcTOKA) after heterologous expression of NcTOKA in yeast. NcTOKA mediated mainly time-dependent outward whole-cell currents, and the reversal potential of these currents indicated that it conducted K
+
efflux. NcTOKA channel gating was sensitive to extracellular K
+
such that channel activation was dependent on the reversal potential for K
+
. However, expression of NcTOKA was able to overcome the K
+
auxotrophy of a yeast mutant missing the K
+
uptake transporters TRK1 and TRK2, suggesting that NcTOKA also mediated K
+
influx. Consistent with this, close inspection of NcTOKA-mediated currents revealed small inward K
+
currents at potentials negative of E
K
. NcTOKA single-channel activity was characterized by rapid flickering between the open and closed states with a unitary conductance of 16 pS. NcTOKA was effectively blocked by extracellular Ca
2+
, verapamil, quinine, and TEA
+
but was insensitive to Cs
+
, 4-aminopyridine, and glibenclamide. The physiological significance of NcTOKA is discussed in the context of its biophysical properties.