bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simple laboratory experiments to observe the manifestations of the sinc function
Authors: Traficante Daniel D. , McGregor Michael M. 
Published: October 2002

AbstractIn NMR spectroscopy, the sinc function manifests itself in a variety of ways, only two of which are discussed in this article. Specifically, the manifestation of this function is discussed in terms of the excitation pulse and in terms of the received signal in high‐resolution liquid‐state NMR. A mathematical theory has been published that predicts the relative intensities and phases of the RFs that excite the nuclei. However, another mathematical treatment is described here that is considerably easier to understand, but it applies only when the tip angle is small, e.g., less than approximately 10°. In addition, this theory is also used to predict the appearance of the sinc “wiggles” that appear when a Fourier transform is performed on a truncated free induction decay (FID) that has been zero‐filled. For the excitation pulse, the intensities of the frequencies delivered to the nuclei follow the classic (sin x)/x, or sinc function, when the tip angle is small. This is demonstrated by a simple experiment. The transmitter offset is stepped in a series of experiments, with each FID summed with all of the previously collected ones. When the series is completed, the FID is Fourier transformed. After correcting for instrumental effects, the resulting spectrum shows that the amplitudes of the excitation frequencies contained within the pulse follow the shape of a sinc function. To demonstrate the formation of sinc “wiggles,” the acquisition time for an FID is set so that it is very heavily truncated and then zero‐filled to eight times the original number of points. The Fourier transform shows that the “wiggles” cross the zero‐intensity line at intervals equal to half‐integer multiples of the reciprocal of the acquisition time, and not at integer multiples, as is often assumed. The difference is that the Fourier transform of a rectangular function of width τ is typically performed by integrating using the limits of −τ/2 to τ/2. In the real spectrum, this would produce zero‐crossing at an integer number of reciprocals of the width of the rectangle, i.e., 1/τ. In the laboratory, however, the limits of the collected signal are from 0 to τ. These limits produce crossings at intervals of 1/(2τ). © 2002 Wiley Periodicals, Inc. Concepts Magn Reson 14: 308–325, 2002
AMPA glutamate receptor subunits in the guinea pig hypothalamus: Distribution and colocalization with progesterone receptor
Authors: Warembourg Maryvonne , Leroy Daniele 
Published: October 2002

AbstractExcitatory amino acids (EAAs), particularly glutamate, have been implicated in the control of luteinizing hormone (LH) secretion through facilitation of gonadotropin‐releasing hormone release. The effects of EAAs are mediated by means of ionotropic glutamate receptors, which are divided into N‐methyl‐D‐aspartate (NMDA) and non‐NMDA (kainate and AMPA) subtypes. Moreover, ovarian steroids are responsible for inducing the preovulatory surge of LH and are involved in the actions of EAAs on LH release. Progesterone is directly involved in the potentiating effect of ovarian steroids on the stimulating effect of AMPA neurotransmission on gonadotropin secretion. To broaden our understanding of the role of hypothalamic AMPA receptors in the steroid‐induced LH surge, we determined the cellular localization of AMPA receptors in the hypothalamus of guinea pigs by using antibodies that recognize the GluR1, GluR2, GluR2/3, or GluR4 subunits, and then we examined the neuroanatomic relationships between these receptors and the progesterone receptor (PR). Different patterns of immunostaining within the preoptic area and hypothalamus were evident with the antibodies to the four subunits with marked contrasts between moderate staining for GluR1, intensely stained structures for GluR2 and GluR2/3, and little specific staining for GluR4. Immunoreactive (IR) neurons were visualized in many regions, including the two regions known to contain a dense population of estradiol‐induced PR‐IR cells: the preoptic periventricular and ventrolateral hypothalamic nuclei. Approximately 60% of GluR1‐IR and 39% of GluR2‐IR cells in the preoptic region possessed PR, whereas 46% of GluR1‐IR and 54% of GluR2‐IR cells in the ventrolateral nucleus expressed PR. These neuroanatomic results suggest that the coordinated actions of progesterone and glutamatergic inputs on mammalian reproductive functions are integrated at the cellular level. J. Comp. Neurol. 453:305–321, 2002. © 2002 Wiley‐Liss, Inc.
The first synthesis of all possible isotopically labelled [D, 13C] methyl group combinations of 2,2‐dimethyl tetralone
Authors: Coumbarides Gregory S. , Eames Jason , Weerasooriya Neluka 
Published: October 2002

AbstractA series of multi‐labelled [D, 13C] 2,2‐dimethyl tetralones were efficiently synthesized using a simple and diverse deprotonation–methylation strategy. All possible ten isotopic combinations were synthesized. The levels of [D, 13C] isotopic incorporation were quantitative and the synthetic yields were high. Copyright © 2002 John Wiley & Sons, Ltd.
Effects of β3‐adrenoceptor stimulation on prostaglandin E2–induced bladder hyperactivity and on the cardiovascular system in conscious rats
Authors: Takeda Hiroo , Yamazaki Yoshinobu , Igawa Yasuhiko , Kaidoh Kouichi , Akahane Satoshi , Miyata Hiroshi , Nishizawa Osamu , Akahane Masuo , Andersson Karl‐Erik 
Published: October 2002

AbstractAims.To investigate the effects of selective β2‐ and selective β3‐adrenoceptor (AR) agonists on prostaglandin (PG) E2‐induced bladder hyperactivity in conscious free‐moving rats.Methods.Female Sprague‐Dawley rats were anesthetized for implantation of bladder, intravenous, and intra‐arterial catheters. The effects of a β3‐AR agonist (CL316,243) on cystometric and cardiovascular parameters were assessed in conscious rats. Intravesical instillation of PGE2 (20–60 μM, 6 mL/hr) in conscious rats produced a concentration‐dependent increase in voiding frequency.Results.In this model i.v. CL316,243 (β3‐AR agonist) reduced basal bladder pressure, increased micturition volume, and prolonged micturition interval in a dose‐dependent manner, without affecting threshold pressure or micturition pressure. On the other hand, i.v. procaterol (β2‐AR agonist) did not counteract the bladder hyperactivity. Atropine (muscarinic antagonist) reduced micturition pressure and micturition volume, and shortened micturition interval. CL316,243 slightly decreased mean blood pressure and increased heart rate only when given at high doses (10 and 100 μg/kg, i.v.). In contrast, procaterol caused a significant decrease in mean blood pressure and a significant increase in heart rate. Atropine significantly increased heart rate.Conclusions.The present results clearly demonstrated that the β3‐AR agonist prolonged the micturition interval without producing significant cardiovascular side effects. The human detrusor, like the rat detrusor, relaxes on β3‐AR stimulation. Provided that these results are valid in humans, selective β3‐AR agonists might be clinically useful for controlling a certain type of bladder overactivity. Neurourol. Urodynam. 21:558–565, 2002. © 2002 Wiley‐Liss, Inc.
Standardization of anal sphincter electromyography: Quantification of continuous activity during relaxation
Authors: Podnar Simon , Mrkaić Mićo , Vodušek David B. 
Published: October 2002

AbstractAim.Sphincter motor units (MUs) are continuously firing during relaxation. The quantification of this activity is a potentially useful electromyographic (EMG) parameter related to the number of MUs innervating the muscle and the level of motor neuron excitation. The aim of the present study was to develop a reliable, quantitative measure of continuous sphincter muscle activity during relaxation.Methods.EMG activity was analyzed during relaxation, 1 minute after insertion of the concentric needle electrode into four sites in the external anal sphincter (EAS) muscle. In 10 control subjects, 8 interference pattern samples were obtained by “turn/amplitude” analysis. In 35 control subjects, a multi‐MUP count of continuously firing motor unit potentials (MUPs) was used, quadruplets with scores of 0–6 obtained, and the lower reference limits (95th percentile) calculated. This approach was then evaluated in 57 patients (182 muscles) with cauda equina or conus medullaris lesion (CECML) and 7 patients (13 muscles) with “idiopathic fecal incontinence.”Results.The lower reference (“outlier”) limits for MUP count were 0 0 6 6 and 0 1 2 2 for the subcutaneous, and 0 0 0 6 and 0 0 1 1 for the deeper EAS muscles. Both patient groups had a significantly diminished number of continuously firing MUPs, which was below the reference range in 43% of the EAS muscles from CECM patients and in 85% of muscles from patients with idiopathic fecal incontinence. In patients with CECML, the decrease in MUP count correlated with the severity of the lesion, as defined by the sensory deficit.Conclusions.MUP count in sphincter muscles during relaxation is technically feasible, and it is a promising tool, particularly in patients with idiopathic fecal incontinence. Neurourol. Urodynam. 21:540–545, 2002. © 2002 Wiley‐Liss, Inc.
4,5‐diaminofluoroscein imaging of nitric oxide synthesis in crayfish terminal ganglia
Authors: Schuppe Hansjürgen , Cuttle Matthew , Chad John E. , Newland Philip L. 
Published: October 2002

AbstractWe have analyzed the synthesis of nitric oxide in the terminal abdominal ganglion of the crayfish using the fluorescent probe 4,5‐Diaminofluoroscein diacetate, DAF‐2 DA. Following DAF‐2 loading, ganglia showed cell‐specific patterns of fluorescence in which the occurrence of strongly fluorescent cell bodies was highest in specific anterior, central, and posterior regions. We found that preincubation with the nitric oxide synthase (NOS) inhibitor L‐NAME prevented much of the initial development of DAF‐2 fluorescence, whereas the inactive isomer D‐NAME had no effect. Washout of preincubated L‐NAME caused increased cell‐specific fluorescence due to endogenous NOS activity. Application of the NOS substrate L‐arginine also resulted in an increase of DAF‐2 fluorescence in a cell‐specific manner. We bath applied the NO donor SNAP to increase exogenous NO levels which resulted in DAF‐2 fluorescence increases in most cells. We therefore presume that the cell‐specific pattern of DAF‐2 fluorescence indicates the distribution of neurones actively synthesizing NO. The similarity between the DAF‐2 staining pattern and previously published studies of NOS activity are discussed. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 361–369, 2002
Patterns and processes in the early evolution of the tetrapod ear
Authors: Clack Jennifer A. 
Published: October 2002

AbstractThis article reviews some of the latest information on the evolution of the tetrapod ear region as seen in the fossil record. It looks at the changes that can be documented across the fish–tetrapod transition, the patterns that they show and what can be inferred of the processes that brought some of them about. These processes include an increased role for neural crest, and heterochronic processes such as pedomorphosis. The earliest tetrapods show a common pattern of a short stout stapes with a large stapedial foramen, that primitively contacted the palatal bones and probably supported the braincase. Modifications to this pattern can be seen in tandem with changes to the occiput and are bound up with changes to jaw and breathing mechanisms. By the Late Carboniferous, tetrapods had diversified into a range of groups showing a wide variety of otic morphologies, some of which were probably tympanic, while others were not, and some which are very different from those found in extant tetrapods. In amniotes, the evolution of a tympanic ear appears to correlate with consolidation and integration of the occiput to the skull roof. Competing phylogenies suggest different numbers of iterations for the origin of a tympanic ear, but a minimum of four separate occasions is implied. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 251–264, 2002
Peptides in apoptosis research
Authors: Salgado Jesús , García‐Sáez Ana J. , Malet Gema , Mingarro Ismael , Pérez‐Payá Enrique 
Published: October 2002

AbstractApoptosis is a complex process that plays a central role in physiological and pathological cell death. This fast evolving research area has experienced incredible development in the past few years. Progress in the knowledge of the structure of many of the main molecular actors of the apoptotic signal transduction pathways has driven the design of synthetic peptides that in some cases can function as simplified versions of their parent proteins. These molecules are contributing to a better understanding of the activity and regulation of apoptotic proteins and also are setting the basis for the discovery of effective drugs to combat important diseases related to apoptosis. Most applications of peptides in apoptosis research are so far related to caspases, caspase regulatory proteins, such as IAPs and Smac, and proteins of the Bcl‐2 family. Additionally, important perspectives are open to other systems, such as the macromolecular assemblies that are responsible for the activation of initiator caspases. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd.
Semen characteristics of the quaker parakeet (Myiopsitta monachus)
Authors: Anderson Susan J. , Bird David M. , Hagen Mark D. 
Published: October 2002

AbstractThis report describes characteristics of semen samples collected from eight captive quaker parakeets (Myiopsitta monachus) using the massage technique. Overall, semen characteristics were (mean±SE, range in parentheses, n=8 males): ejaculate volume 1.96±0.26μl (1.02–2.96), sperm concentration 346.6±64.6 million/ml (74.8–579.3), and number of sperm per ejaculate 0.71±0.16 million (0.09–1.53). Significant differences were observed between males for all three semen characteristics. Semen pH for the eight males ranged from 8.05 to 8.5. The semen samples were collected early in the breeding season, so the data reported may not be representative of ejaculates from males in peak breeding condition. However, this study provides the first rigorous semen data from this species and demonstrates that good‐quality semen samples, suitable for artificial insemination, can be collected regularly from quaker parakeets using the massage technique. Zoo Biol 21:507–512, 2002. © 2002 Wiley‐Liss, Inc.
Molecular Mechanisms of Resistance to Human Immunodeficiency Virus Type 1 with Reverse Transcriptase Mutations K65R and K65R+M184V and Their Effects on Enzyme Function and Viral Replication Capacity
Authors: White Kirsten L. , Margot Nicolas A. , Wrin Terri , Petropoulos Christos J. , Miller Michael D. , Naeger Lisa K. 
Published: October 2002

ABSTRACTHuman immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) resistance mutations K65R and M184V result in changes in susceptibility to several nucleoside and nucleotide RT inhibitors. K65R-containing viruses showed decreases in susceptibility to tenofovir, didanosine (ddI), abacavir, and (−)-β-d-dioxolane guanosine (DXG; the active metabolite of amdoxovir) but appeared to be fully susceptible to zidovudine and stavudine in vitro. Viruses containing the K65R and M184V mutations showed further decreases in susceptibility to ddI and abacavir but increased susceptibility to tenofovir compared to the susceptibilities of viruses with the K65R mutation. Enzymatic and viral replication analyses were undertaken to elucidate the mechanisms of altered drug susceptibilities and potential fitness defects for the K65R and K65R+M184V mutants. The relative inhibitory capacities (Ki/Km) of the active metabolites of tenofovir, ddI, and DXG were increased for the RT containing the K65R mutation compared to that for the wild-type RT, but the relative inhibitory capacity of abacavir was only minimally increased. For the mutant viruses with the K65R and M184V mutations, the increase in tenofovir susceptibility compared to that of the mutants with K65R correlated with a decrease in the tenofovir inhibitory capacity that was mediated primarily by an increasedKmof dATP. The decrease in susceptibility to ddI by mutants with the K65R and M184V mutations correlated with an increase in the inhibitory capacity mediated by an increasedKi. ATP-mediated removal of carbovir as well as small increases in the inhibitory capacity of carbovir appear to contribute to the resistance of mutants with the K65R mutation and the mutants with the K65R and M184V mutations to abacavir. Finally, both the HIV-1 K65R mutant and, more notably, the HIV-1 K65R+M184V double mutant showed reduced replication capacities and reduced RT processivities in vitro, consistent with a potential fitness defect in vivo and the low prevalence of the K65R mutation among isolates from antiretroviral agent-experienced patients.
The Immunosuppressant Rapamycin Represses Human Immunodeficiency Virus Type 1 Replication
Authors: Roy Jocelyn , Paquette Jean-Sébastien , Fortin Jean-François , Tremblay Michel J. 
Published: October 2002

ABSTRACTThe immunosuppressive macrolide rapamycin is used in humans to prevent graft rejection. This drug acts by selectively repressing the translation of proteins that are encoded by an mRNA bearing a 5′-polypyrimidine tract (e.g., ribosomal proteins, elongation factors). The human immunodeficiency virus type 1 (HIV-1) carries a polypyrimidine motif that is located within thetatexon 2. Treatment of human T lymphoid cells with rapamycin resulted in a marked diminution of HIV-1 transcription when infection was performed with luciferase reporter T-tropic and macrophage-tropic viruses. Replication of fully infectious HIV-1 particles was abolished by rapamycin treatment. The rapamycin-mediated inhibitory effect on HIV-1 production was reversed by FK506. The anti-HIV-1 effect of rapamycin was also seen in primary human cells (i.e., peripheral blood lymphocytes) from different healthy donors. Rapamycin was shown to diminish basal HIV-1 long terminal repeat gene expression, and the observed effect of rapamycin on HIV-1 replication seems to be independent of the virus-specific transactivating Tat protein. A constitutive β-actin promoter-based reporter gene vector was unaffected by rapamycin treatment. Kinetic virus infection studies and exposure to reporter viruses pseudotyped with heterologous envelope proteins (i.e., amphotropic murine leukemia virus and vesicular stomatitis virus G) suggested that rapamycin is primarily affecting the life cycle of HIV-1 at a transcriptional level. Northern blot analysis confirmed that this compound is selectively targeting HIV-1 mRNA synthesis.
Direct Evidence that Saquinavir Is Transported by Multidrug Resistance-Associated Protein (MRP1) and Canalicular Multispecific Organic Anion Transporter (MRP2)
Authors: Williams Gregory C. , Liu Angela , Knipp Gregory , Sinko Patrick J. 
Published: October 2002

ABSTRACT

To determine if saquinavir mesylate (saquinavir) is a substrate of human multidrug resistance-associated protein 1 (hMRP1 [ABCC1]) or hMRP2 (cMOAT, or ABCC2), MDCKII cells that overexpress either hMRP1 (MDCKII-MRP1) or hMRP2 (MDCKII-MRP2) were used to investigate saquinavir's cytotoxicity and transport in comparison with those of control MDCKII wild-type (MDCKII/wt) cells. Cytotoxicity was assessed with the mitochondrial marker MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium], and saquinavir transport was measured directly through the cell monolayers. GF120918 (an inhibitor of P glycoprotein, but not of the MRP family) and MK-571 (an MRP family inhibitor) were used to delineate the specific contributions of these transporters to saquinavir cytotoxicity and transport. In the presence of GF120918 and increasing saquinavir concentrations, the MDCKII-MRP1 (50% lethal dose [LD
50
] = 10.5 μM) and MDCKII-MRP2 (LD
50
= 27.1 μM) cell lines exhibited statistically greater viability than the MDCKII/wt cells (LD
50
= 7.8 μM). Saquinavir efflux was directional, not saturable, and was inhibited by MK-571 (35 and 75 μM) in all cell lines. The ratios of saquinavir (3 μM) basolateral to apical permeability (i.e., efflux ratios) for the MDCKII/wt, MDCKII-MRP1, and MDCKII-MRP2 cell monolayers were 2.6, 1.8, and 6.8, respectively. The MDCKII-MRP1 cells have a significantly reduced saquinavir efflux ratio relative to MDCKII/wt cells, due to basolaterally directed transport by hMRP1 competing with endogenous, apically directed canine MRP2. The MDCKII-MRP2 cells have a significantly increased saquinavir efflux ratio relative to MDCKII/wt cells, due to the additive effects of the apically directed transport by hMRP2 and endogenous MRP2. Collectively, the cytotoxicity and transport results provide direct evidence that saquinavir is transported by MRP1 and MRP2.
Effects of Azithromycin on Shiga Toxin Production by
Escherichia coli
and Subsequent Host Inflammatory Response
Authors: Ohara Tatsuki , Kojio Seiichi , Taneike Ikue , Nakagawa Saori , Gondaira Fumio , Tamura Yukiko , Gejyo Fumitake , Zhang Hui-Min , Yamamoto Tatsuo 
Published: October 2002

ABSTRACT

Shiga toxin (Stx)-producing
Escherichia coli
(STEC) colonizes the human intestinal mucosa, produces Stx from phage, and causes the development of hemolytic-uremic syndrome via Stx-induced inflammatory cytokine production. Azithromycin exhibited strong in vitro activity against STEC without inducing Stx-converting phage, in marked contrast to norfloxacin. Azithromycin decreased the tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 production from Stx-treated human peripheral mononuclear cells or monocytes to a greater extent than did clarithromycin. In Stx-injected mice, azithromycin significantly suppressed Stx-induced TNF-α, IL-1β, and IL-6 levels in serum and improved the outcome as assessed by survival rate. In the STEC oral infection experiment using immature mice immediately after weaning (weaned immature-mouse model), all mice died within 7 days postinfection. Azithromycin administration gave the mice 100% protection from killing, while ciprofloxacin administration gave them 67% protection. The data suggest that azithromycin (at least at higher concentrations) has a strong effect on Stx production by STEC and on the Stx-induced inflammatory host response and prevents death in mice. Azithromycin may have a beneficial effect on STEC-associated disease.
An Elevated Mutation Frequency Favors Development of Vancomycin Resistance in
Staphylococcus aureus
Authors: Schaaff Franziska , Reipert Andrea , Bierbaum Gabriele 
Published: October 2002

ABSTRACT

The emergence of intermediate vancomycin resistance, mainly in methicillin-resistant
Staphylococcus aureus
strains, has become a great concern. Thorough characterization of clinical and laboratory vancomycin-intermediately resistant
S. aureus
(VISA) strains identified multiple, resistance-associated changes most probably due to stepwise mutations. We hypothesized that an elevated mutation frequency as found, e.g., in mutator strains defective in DNA mismatch repair could allow rapid acquisition of adaptive mutations in the presence of vancomycin. We therefore subjected
S. aureus
RN4220 and its isogenic mutator strain, the
mutS
-knockout mutant RN4220Δ
mutS
, to a stepwise vancomycin selection procedure. Vancomycin resistance evolved much more quickly in the mutator background than in the wild type (5 versus 19 passages, respectively). In addition, a higher resistance level could be reached (MIC, 32 versus 4 μg/ml, respectively). The susceptibility to other antibiotics with the exception of teicoplanin remained unchanged. Concomitantly with increasing vancomycin resistance, a loss of phage typeability and differences in growth behavior as well as an improved ability to regrow at high vancomycin concentrations were observed. In conclusion, an elevated mutation rate in
S. aureus
led to the rapid development of vancomycin resistance, indicating that a high mutation frequency could be one of the factors that favor the emergence of vancomycin resistance in
S. aureus
.