bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Aims.

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

Aim.

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

We 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

This 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

Apoptosis 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

This 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

Human 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

The 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

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

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

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
.
Infection dynamics of a sexually transmitted nematode (Mehdinema alii) in the decorated cricket (Gryllodes sigillatus)
Authors: Luong Lien T , Kaya Harry K
Published: October 2002

We investigated the transmission dynamics of a sexually transmitted nematode, Mehdinema alii, in the decorated cricket, Gryllodes sigillatus. Adult crickets were experimentally inoculated with infective stages of the nematode, called dauerlarvae, to determine the role of the female cricket in nematode transmission. We found that female crickets serve only as a means of mechanical transmission, so nematodes do not require passage through a female cricket to be infective. Dauerlarvae were experimentally placed on the genitalia of both sexes. In the male, the dauerlarvae migrated into the gut and proceeded to develop into adult nematodes, whereas those that were inoculated into the female genitalia failed to migrate into the gut. When dauerlarvae were inoculated directly into the female rectum, the nematodes failed to develop. Therefore, the female gut is not a suitable environment for nematode development. Dauerlarvae persisted in the female cricket for up to 12 days post inoculation and remained infective to male crickets.
Habitat associations of American badgers in southeastern British Columbia
Authors: Apps Clayton D , Newhouse Nancy J , Kinley Trevor A
Published: October 2002

American badgers (Taxidea taxus) are endangered in British Columbia due to habitat loss and human-caused mortality. To better understand human impacts and to promote conservation planning, we described badger habitat relationships. At two spatial scales, we analyzed selection by 12 radio-implanted resident badgers for soil composition, forest overstory, land cover, vegetation productivity, terrain, and human influence. At a broad (23.8 km2) landscape scale, soil parent-material associations were positive with glaciolacustrine and glaciofluvial and negative with colluvial. Soil-order associations were positive with brunisols and regosols and negative with podzols and luvisols. Association with fine sandy-loam texture was positive. Associations were negative with forested habitats and positive with open range, agricultural habitats, and linear disturbances. Associations were negative with elevation, slope, terrain ruggedness, and both vegetation productivity and moisture. At a fine (14.5 ha) scale, associations were positive with glaciofluvial, fine sandy-loam textured, and well-drained soils. Associations were negative with colluvial soils, forest cover, vegetation moisture, elevation, and ruggedness. Associations with open range and southern aspects were positive. The linear combination of a subset of variables could explain and predict habitat selection. At this range extent, natural conditions may restrict badger occurrence, increasing badger sensitivity to human factors that influence habitat quality and mortality.
LINEAR AND INTEGER PROGRAMMING TECHNIQUES FOR COOPERATIVE GAMES
Authors: Fang Qizhi , Zhu Shanfeng
Published: October 2002

Let Γ = (N, v) be a cooperative game with the player set N and value function v : 2N → R. A solution of the game is in the core if no subset of players could gain advantage by breaking away from the grand coalition of all players. This paper surveys theoretical results on the cores for some cooperative game models. These results proved that the linear program duality characterization of the core is a very powerful tool. We will focus on linear and integer programming techniques applied in this area.
GENERALIZATIONS OF THE SIXTH ORDER TERM IN THE SKYRME LAGRANGIAN
Authors: KUMAR RAJESH , CHATTOPADHYAY P. K.
Published: October 2002

Various generalizations of the sixth order term (~ Tr BμBμ) in the Skyrme Lagrangian originally proposed by Jackson et al. Mare investigated. Such generalized sixth order terms when added to the Skyrme Lagrangian, give rise to considerable improvement in the fitted value of pion decay constant. Also, the agreement between the theoretically calculated and experimental values of other physical quantities such as the axial coupling constant improves.
CORRELATIONS AND THE RELATIVISTIC STRUCTURE OF THE NUCLEON SELF-ENERGY
Authors: MÜTHER H. , ULRYCH S. , TOKI H.
Published: October 2002

A key point of Dirac-Brueckner-Hartree-Fock calculations for nuclear matter is to decompose the self-energy of the nucleons into Lorentz scalar and vector components. A new method is introduced for this decomposition. It is based on the dependence of the single-particle energy on the small components in the Dirac spinors used to calculate the matrix elements of the underlying NN interaction. The resulting Dirac components of the self-energy depend on the momentum of the nucleons. At densities around and below the nuclear matter saturation density this momentum dependence is dominated by the non-locality of the Brueckner G matrix. At higher densities these correlation effects are suppressed and the momentum dependence due to the Fock exchange terms is getting more important. Differences between symmetric nuclear matter and neutron matter are discussed. Various versions of the Bonn potential are considered.
Anti-μ-opioid-receptor IgG antibodies are commonly present in serum from healthy blood donors: evidence for a role in apoptotic immune cell death
Authors: Macé Gaëtane , Jaume Martial , Blanpied Catherine , Stephan Lionel , Coudert Jérôme D. , Druet Philippe , Dietrich Gilles
Published: October 2002

We previously observed the presence of anti-human μ-opioid-receptor (anti-hMOR) autoantibodies in IgG pools prepared from several thousand healthy blood donors. These autoantibodies behaved agonistically because of their ability to bind to the first and third extracellular loops of the receptor. In this study, we found that each healthy donor's serum contained anti-hMOR IgG autoantibodies with a specific activity against both the first and the third extracellular loops of the receptor. Because of the inability of IgG to cross the blood-brain barrier, we investigated the effects of the expression of anti-hMOR autoantibodies on immune cells. In analogy to studies of the effects of morphine, we investigated the ability of antibodies to sensitize splenocytes to Fas (CD95)-mediated apoptosis. We took advantage of the high sequence homology between murine MOR and hMOR extracellular loops to estimate the effect on murine splenocytes of anti-hMOR antibodies raised by immunizing mice. Splenocytes from mice injected with Chinese hamster ovary (CHO) cells expressing MOR were sensitized to Fas-mediated apoptosis, whereas those from mice injected with CHO cells or phosphate-buffered saline were not. Similar sensitization to Fas-mediated apoptosis was observed in splenocytes from mice undergoing passive transfer either with IgG from mice previously immunized against CHO cells expressing MOR or with IgG directed against the first and third extracellular loops of the receptor. Together, our data show that anti-MOR autoantibodies are commonly expressed in healthy humans and could participate in the control of lymphocyte homeostasis by promoting Fas-mediated apoptosis.
KSHV- and EBV-associated germinotropic lymphoproliferative disorder
Authors: Du Ming-Qing , Diss Tim C. , Liu Hongxiang , Ye Hongtao , Hamoudi Rifat A. , Cabeçadas José , Dong Henry Y. , Harris Nancy Lee , Chan John K. C. , Rees John W. , Dogan Ahmet , Isaacson Peter G.
Published: October 2002

Kaposi sarcoma–associated herpesvirus (KSHV) is known to be associated with 3 distinct lymphoproliferative disorders: primary effusion lymphoma (PEL), multicentric Castleman disease (MCD), and MCD-associated plasmablastic lymphoma. We report 3 cases of a previously undescribed KSHV-associated lymphoproliferative disorder. The disease presented as localized lymphadenopathy and showed a favorable response to chemotherapy or radiotherapy. Histologically, the lymphoproliferation is characterized by plasmablasts that preferentially involved germinal centers of the lymphoid follicles, forming confluent aggregates. They were negative for CD20, CD27, CD79a, CD138, BCL6, and CD10 but showed monotypic κ or λ light chain. Clusters of CD10+CD20+ residual follicle center cells were identified in some of the follicles. The plasmablasts were positive for both KSHV and EBV, and most of them also expressed viral interleukin-6 (vIL-6). Unexpectedly, molecular analysis of whole tissue sections or microdissected KSHV-positive aggregates demonstrated a polyclonal or oligoclonal pattern of immunoglobulin (Ig) gene rearrangement. The plasmablasts showed somatic mutation and intraclonal variation in the rearranged Ig genes, and one case expressed switched Ig heavy chain (IgA), suggesting that they originated from germinal center B cells. We propose calling this distinctive entity “KSHV-associated germinotropic lymphoproliferative disorder.”
Protection against thrombosis in mice lacking PAR3
Authors: Weiss Ethan J. , Hamilton Justin R. , Lease Katy E. , Coughlin Shaun R.
Published: October 2002

The recent observation that knock-out of protease-activated receptor-4 (PAR4) ablates thrombin signaling in mouse platelets and protects against ferric chloride–induced thrombosis of mouse mesenteric arterioles suggests that thrombin's actions on platelets can play an important role in thrombosis. Complete ablation of thrombin signaling would be difficult to achieve in human beings because human platelets have 2 thrombin receptors that are each capable of mediating transmembrane signaling. However, it is possible that complete ablation of thrombin signaling in platelets is not necessary for an antithrombotic effect. In mouse platelets, PAR3 functions as a cofactor that binds thrombin and promotes productive cleavage of PAR4, and thrombin responses are decreased but not absent inPar3−/− platelets. We now report thatPar3−/− mice were protected against ferric chloride–induced thrombosis of mesenteric arterioles and against thromboplastin-induced pulmonary embolism. Surprisingly,Par3−/− and Par4−/−mice showed similar degrees of protection in these models and similar prolongation of tail bleeding times. Thus, even a partial decrease in mouse platelet responsiveness to thrombin protected against thrombosis and impaired hemostasis in some settings. These results demonstrate the importance of PAR3's unusual cofactor function and underscore the relative importance of thrombin's actions on platelets in vivo. They also suggest that PAR inhibition might be explored for the prevention or treatment of thrombosis in human beings.
Functional β1 - and β2-adrenoceptors in the left and right atrium of pre-hypertensive rats
Authors: Doggrell Sheila A
Published: October 2002

There is a small increase in the functional β2-adrenoceptor response on the spontaneously hypertensive rat (SHR) left atrium in the early stages of hypertension. In the present study, the functional β1 - and β2-adrenoceptors of the left and right atrium in SHR pre-hypertension and age-matched (5-week-old) Wistar Kyoto (WKY) rats were characterized. Contractility methods with isoprenaline, T-0509 (a selective β1-adrenoceptor agonist) and procaterol (a selective β2-adrenoceptor agonist) were used. At 5 weeks, the SHRs were pre-hypertensive. Isoprenaline was more potent on the left atrium of 5-week-old SHRs than WKY rats. Bisoprolol, a selective β1-adrenoceptor antagonist, was more potent against isoprenaline and T-0509 on the SHR than WKY rat left atrium. ICI 118,551, a selective β2-adrenoceptor antagonist, was more potent against procaterol and T-0509 on the SHR than WKY rat left atrium. The results with bisoprolol and ICI 118,551 suggest that there are more functional β1- and β2-adrenoceptors on the left atrium of 5-week-old SHRs than WKY rats. Isoprenaline, T-0509 and procaterol were equipotent on the right atrium of 5-week-old WKY rats and SHRs. Bisoprolol was more potent against isoprenaline, T-0509 and procaterol on the SHR than WKY rat right atrium. ICI 118,551 was more potent against T-0509, but not isoprenaline and procaterol, on the SHR than WKY rat left atrium. This suggests there are more functional β1-adrenoceptors, and probably more functional β2-adrenoceptors, on the right atrium of 5-week-old SHRs than WKY rats. These functional differences in β1 - and β2-adrenoceptor-mediated responses of the left and right atria of pre-hypertensive SHRs cannot be caused by hypertension, and may be associated with the onset of hypertension.
In-vitro transfer of nitazoxanide across the intestinal epithelial barrier
Authors: Matysiak-Budnik Tamara , Mégraud Francis , Heyman Martine
Published: October 2002

Nitazoxanide is a thiazolide compound that exhibits antimicrobial properties against helminths, protozoa, anaerobic bacteria and also Helicobacter pylori. The mucosal diffusion of this new drug has not been studied. The aim of this study was to examine the transport of radiolabelled nitazoxanide across the epithelial barrier according to the mode (mucosal or serosal) of drug administration. HT29-19A intestinal epithelial cells, grown as monolayers on microporous filters, were used as an epithelial model. In a short-term (100 min) transport study, the apical to basal and the basal to apical transport of nitazoxanide across the monolayers was studied in an Ussing chamber. In a long-term (24 h) study, the transport of the drug and its intracellular accumulation were studied in filter-grown epithelial monolayers kept in culture plates. In the short-term transport study, both the apical and basal fluxes achieved a steady state after 70 min and there was no significant difference between the apical to basal (3991 ± 1001 ng h−1 cm−2) and the basal to apical (4246 ± 856 ng h−1 cm−2) nitazoxanide fluxes. In the long-term transport study, after apical or basal drug application, a gradual increase in the drug concentration in the opposite compartment was noted, which reached similar values for apical and basal fluxes (2497 ± 125 and 2309 ± 81 ng mL−1, respectively) after 24 h. Moreover, a rapid, although transitory, intracellular accumulation of nitazoxanide was observed at 10 min after apical (299 ± 25 ng/106 cells) and basal (124 ± 10 ng/106 cells) drug application, but decreased thereafter. There is an important transepithelial transport of nitazoxanide across the digestive epithelial monolayer with a rapid intracellular accumulation of the drug. No difference between the apical to basal and basal to apical fluxes of the drug was observed, suggesting that both topical and systemic modes of action of this antibiotic are successful.
Functionalization of Carbon Material by Surface Grafting of Polymers
Authors: Tsubokawa Norio
Published: October 2002

Recent advances in surface grafting of polymers onto carbon materials, such as carbon black, graphite powder, and carbon fiber, and the application of polymer-grafted carbon materials as a novel functional materials have been mainly reviewed. The grafting of polymers onto the surface was achieved by (1) grafting onto process, (2) grafting from process, (3) polymer reaction process, and (4) stepwise growth by dendrimer synthesis methodology. For the grafting, surface functional groups, such as carboxyl and phenolic hydroxy groups, were used as grafting sites. For example, in the living cationic polymerization initiated by carbon black/ZnCl2 system, carboxyl groups on the surface acted as initiating site and grafting site. In the surface grafting, polycondensed aromatic rings of carbon materials could be used as grafting sites by using ligand exchange reaction of polymers containing ferrocene moieties. It was demonstrated that, by the grafting of polymers onto carbon black surface, the dispersibility in solvent and the surface wettability were readily controlled by pH and temperature. By postgrafting of hydrophilic polymer to grafted hydrophobic chain on carbon black, amphiphilic carbon black was obtained. The applications of crystalline polymer-grafted carbon black as a novel gas sensor material and a positive temperature coefficient material are summarized.
Effect of Water and Oxygen Contents on the Decomposition of Gaseous Trichloroethylene in Air under Electron Beam Irradiation
Authors: Hakoda Teruyuki , Hashimoto Shoji , Kojima Takuji
Published: October 2002

An electron beam (EB) treatment of gaseous trichloroethylene (TCE) in air was studied as a purification method of off-gases containing gaseous chloroethylenes. The model air containing TCE at input concentrations of 5–75 ppmv, detected mostly in actual off-gases, was irradiated with 1-MeV EBs in a gas-flow vessel at 10 L/min under the conditions of atmospheric pressure, 298 K, and different H2O contents. The decomposition of 75 ppmv TCE was also examined in humid air under different O2 contents of 1 × 103–2.1 × 105 ppmv. In the existence of H2O and O2 contents with ≥ 3 × 102 ppmv and ≥ 5 × 103 ppmv, respectively, the decomposition ratios of TCE were enhanced and TCE was decomposed into 83.0 ± 1.5% of dichloroacetyl chloride (DCAC) and 17.5 ± 0.6% of carbonyl chloride (COCl2) independently of the input TCE concentrations based on the carbon balance. Trichloroethylene of 5–75 ppmv was effectively decomposed by the OH radical through Cl-radical chain oxidation under the above-mentioned air conditions.
Effect of urine storage on urinary uric acid concentrations
Authors: Yamakita Jun-Ichi , Yamamoto Tetsuya , Moriwaki Yuji , Takahashi Sumio , Tsutsumi Zenta , Hada Toshikazu
Published: October 2002

Accurate determination of serum and urinary uric acid concentrations is essential for the diagnosis and classification of gout according to uric acid metabolism derangement. Urine and/or serum samples are often kept at either 4°C or 20°C until assayed, when a large number of samples are handled simultaneously. Our preliminary study indicated a significant decrease in urinary uric acid concentration after preservation, regardless of the storage temperature. Uric acid crystals were often observed in these cases which showed a marked decrease in urinary uric acid concentration after storage. In the present study, we sought the factor(s) that might cause this decrease in urinary uric acid concentration, as well as measures to overcome the problem. High urinary uric acid concentration and low pH proved to play major roles in the decrease in urinary uric acid concentration after storage. In contrast, dilution of the urine samples before storage resulted in no significant change in urinary uric acid concentration. Based on these results, we recommend diluting urine before storage for determination of uric acid concentration and avoiding underestimation.
A reliable non-separation fluorescence quenching assay for total glycated serum protein: a simple alternative to nitroblue tetrazolium reduction
Authors: Blincko Stuart , Colbert D Avid , John W Garry , Edwards Raymond
Published: October 2002

A simple non-separation assay for the measurement of total glycated serum protein is described. It was found that the fluorescence intensity of a solution of a fluorescein-boronic acid derivative was quenched in proportion to the amount of serum added. This led to the development of an assay in which 10 µL of serum is added to 4 mL of a solution of the fluorescein-boronic acid derivative and the fluorescence intensity is measured after 15 min. The results, as measured by drop in fluorescence intensity, calibrated by a single standard, were compared with the results for nitroblue tetrazolium (NBT) reduction of fructosamine and showed good correlation ( r=0·936, n=114). The intra-assay precision (seven samples each measured 10 times) was less than 2·1% (concentration range 190-660 µmol/L); inter-assay precision for seven samples in 10 assays was less than 2·5% (over the same concentration range). Dilution of serum that had a high concentration of total glycated protein showed the assay to be linear. Serum samples (with low, medium and high total glycated protein concentrations) showed less than 2·1% difference from base results with added glucose (up to 60 mmol/L), less than 9·7% difference with added bilirubin (up to 250 µmol/L) and less than 6·9% with added triglycerides (up to 50 mmol/L). Addition of haemoglobin (up to 0·9 g/dL) with high glycation (11·7% HbA 1c) to plasma (298 µmol/L total glycated protein) showed less than 10% difference from the base result. Assays performed over a range of temperatures (12- 34 C) showed no significant differences in the results. The assay gives similar results to the currently used NTB method but with significantly less susceptibility to interferences. As such the method should be a useful aid in the management of diabetes.
Transient pituitary hypothyroidism in a patient with ectopic adrenocorticotrophic hormone secretion
Authors: Rodríguez-Espinosa J , Urgell E , Montesinos J , Omingo P D , Webb S M
Published: October 2002

We report the case of a 55-year-old woman who presented with hypercortisolism secondary to ectopic adrenocorticotrophic hormone secretion and severe non-thyroidal illness syndrome (NTIS) due to metastatic small cell lung carcinoma associated with severe infections. The patient initially showed hormonal profiles of pituitary hypothyroidism and gonadal hypofunction. After decrease in cortisol production following treatment with chemotherapy and metyrapone, serum thyroid hormones and thyroid-stimulating hormone (TSH) concentrations normalized. Study of the relative contributions of cortisol and pro-inflammatory cytokines (interleukin-6 and tumour necrosis factor α) to the overall variability in thyroid function tests disclosed a significant and independent effect of serum cortisol on serum TSH concentrations; the variability in free thyroid hormone concentration was explained only by changes in TSH concentration. These observations indicate that cortisol could be the major determinant of changes in serum TSH concentrations in clinical conditions accompanied by hypercortisolism, as occurs in NTIS.
'Glucose meter hypoglycaemia': often a non-disease
Authors: Gama R , Anderson N R , Marks V
Published: October 2002

The diagnosis of hypoglycaemia depends upon the demonstration of a low blood glucose concentration during a spontaneous symptomatic episode. Glucose monitoring devices may misdiagnose many healthy individuals with nonspecific symptoms as having hypoglycaemia. We present three illustrative cases of 'glucose meter non-hypoglycaemia'.
Effect of vitamin E supplementation on circulating cell adhesion molecules pre- and post-coronary angioplasty
Authors: Ferns G A A , Forster L A , William J C , Tull S P , Verma P K , Starkey B , Gershlick A H
Published: October 2002

The soluble adhesion molecules P-selectin (sP-selectin) and intercellular adhesion molecule-1 (sICAM-1) are derived from platelets and endothelial cells. Circulating concentrations of these soluble adhesion molecules are raised in patients with atherosclerosis and following percutaneous transluminal coronary angioplasty (PTCA). We have investigated the effects of vitamin E supplements (800 IU/day) on circulating plasma ICAM-1 and P-selectin levels pre- and post-PTCA. Patients, randomized to group, were pre-treated with vitamin E or placebo (soybean oil) for 1 month before routine PTCA. Plasma sICAM-1 and sP-selectin were measured by enzyme-linked immunosorbent assay on blood taken immediately pre- and post-PTCA. Total protein and α-tocopherol were measured on the same samples. Plasma α-tocopherol concentrations increased in patients receiving vitamin E: 19·1 (1·5) [mean (standard error of the mean, SEM)] mg/mL post-PTCA versus 13·9 (0·6) mg/mL pre-PTCA ( n=23; P<0·01). Plasma sP-selectin and sICAM-1 levels were not significantly increased following PTCA in the vitamin E group. Pre-angioplasty mean (SEM) plasma sP-selectin concentration in the vitamin E group was 8·83 (0·97) ng/mg protein; the corresponding mean post-angioplasty value was 9·34 (0·89) ng/mg protein ( P=0·85). The mean (SEM) pre-angioplasty sICAM-1 concentration in this group was 2·18 (0·24) ng/mg protein, and was 2·20 (0·23) ng/ mg protein following angioplasty ( P=0·84). In the placebo group ( n=24) there was a significant increase in mean (SEM) sP-selectin concentration following angioplasty, from 7·48 (0·73) to 9·70 (0·78) ng/mg protein ( P<0·05). The change (mean, SEM) in plasma sP-selectin concentration following angioplasty was significantly greater for the placebo group [2·22 (0·50) ng/mg protein] than for the group receiving vitamin E [0·50 (0·50) ng/mg protein] ( P<0·02). This difference remained significant ( P<0·05) even after adjustment for pre-angioplasty P-selectin concentrations. Mean (SEM) plasma sICAM-1 concentrations remained unchanged following angioplasty [preangioplasty: 2·16 (0·20) ng/mg protein; post-angioplasty: 1·97 (0·13) ng/mg protein]. Vitamin E may therefore limit platelet or endothelial activation during PTCA.
Apolipoprotein E polymorphism and serum lipoprotein(a) concentrations in a Korean male population
Authors: Chun Sail , Min Won-Ki , Kim Jong-Won , Park Hyosoon , Jang Seongsoo , Yang Sung-Eun , Kim Jin Q
Published: October 2002

The purpose of this study was to investigate the effect of apolipoprotein E polymorphism on lipoprotein(a) metabolism by comparing serum lipoprotein(a) concentration with apolipoprotein E genotype in a Korean male population whose high molecular weight (HMW) lipoprotein(a) frequency was 95-98%. Serum lipoprotein(a), total cholesterol, triglyceride and high-density lipoprotein-cholesterol concentrations were measured and the apolipoprotein E genotype determined in 1189 healthy Korean males. The medians of serum lipoprotein(a) concentration in the apoE 2/3 group (0.105g/L) and the apoE 3/4 group (0·116g/L) were significantly lower than that in the apoE 3/3 group (0·155g/L; P<0·001). The medians of serum triglyceride were 1·497mmol/L in the apoE 2/3 group, 1·356mmol/L in the apoE 3/4 group, and 1·452mmol/L in the apoE 3/3 group ( P<0·05). With the significant difference in the serum lipoprotein(a) concentration in Korean males according to apolipoprotein E genotype, and with the negative correlation between serum triglyceride concentration and serum lipoprotein(a) concentration, it is suggested that apolipoprotein E polymorphism and serum triglyceride participate in the metabolism of lipoprotein(a) with HMW.
Pseudohyperkalaemia caused by recentrifugation of blood samples after storage in gel separator tubes
Authors: Hira Kenji , Ohtani Yoshito , Rahman Mahbubur , Noguchi Yoshinori , Shimbo Takuro , Fukui Tsuguya
Published: October 2002

Because hyperkalaemia above a certain level is life-threatening, erroneous interpretation of serum potassium concentration may misguide and complicate diagnostic procedures. We investigated a number of cases with pseudohyperkalaemia, which was assumed to have been caused by the recentrifugation of blood samples after storage in gel separator tubes. The time trend of serum potassium concentration was explored before (January-March 1997) and after (May-July 1997) ceasing the practice of recentrifuging blood samples after overnight storage. Next, we conducted an experiment on a volunteer's serum. The sample was divided into two groups and centrifuged once (control group) or twice (recentrifugation group). For both groups, serum potassium concentrations were measured immediately, and at 24, 48 and 72h. For the recentrifugation group, the second centrifugation was done just before the measurement. The time series study showed that the mean serum potassium concentrations measured after overnight storage were 4·68 (95% CI: 4·60-4·76)mmol/L before and 4·14 (4·07-4·20)mmol/L after ceasing the practice of recentrifugation. The experiment showed that the mean serum potassium concentrations in the control group versus the recentrifugation group were 3·95 (95% CI: 3·89-4·01)mmol/L versus 4·05 (3·92-4·17) immediately ( P=0·0979), 3·95 (3·89-4·01) versus 5·95 (5·61-6·29) at 24h ( P=0·0001), 4·13 (4·05- 4·22) versus 6·90 (6·46-7·34) at 48h ( P=0·0001), and 4·22 (3·85-4·58) versus 7·61 (6·94-8·30) at 72h ( P<0·0001). Recentrifugation of blood samples after storage causes a spurious rise in serum potassium concentration to the degree of clinical significance. Clinicians and biochemists should take appropriate measures to stop this practice.
Useful tests on pleural fluid that distinguish transudates from exudates
Authors: Porcel J M , Vives M , De Vera M C Vicente , Cao G , Rubio M , Rivas M C
Published: October 2002

We aimed to compare the classic Light's criteria with different testing strategies in an effort to improve the accuracy of pleural fluid (PF) categorization. Thirty-two patients with transudates and 140 with exudates on the basis of their clinical diagnosis were entered into the study. We examined the discriminative properties of 10 analytes in the identification of PF, both singly and in combination with an 'or' rule, to see which was best in distinguishing a transudate from an exudate. A combination of PF lactate dehydrogenase (LD) 7 307 U/L (two-thirds of the upper limit of the serum LD reference range) with either PF cholesterol 7 1·55 mmol/L or PF to serum protein ratio 7 0.5 had a diagnostic accuracy similar to that of Light's criteria. We suggest the use of PF LD and cholesterol in combination as an alternative method for distinguishing pleural transudates from exudates. This test combination avoids the need for venepuncture and the simultaneous collection of a blood sample.