bluuebunny/crossref_metadata_2025 huggingface dataset:
The Kir6.2‐F333I mutation differentially modulates KATP channels composed of SUR1 or SUR2 subunits
Authors: Tammaro Paolo , Ashcroft Frances
Published: March 2007

Mutations in Kir6.2, the pore‐forming subunit of the KATP channel, that reduce the ability of ATP to block the channel cause neonatal diabetes. The stimulatory effect of MgATP mediated by the regulatory sulphonylurea receptor (SUR) subunit of the channel may also be modified. We compared the effect of the Kir6.2‐F333I mutation on KATP channels containing SUR1, SUR2A or SUR2B. The open probability of Kir6.2/SUR1 channels, or a C‐terminally truncated form of Kir6.2 expressed in the absence of SUR, was unaffected by the mutation. However, that of Kir6.2/SUR2A and Kir6.2/SUR2B channels was increased. In the absence of Mg2+, ATP inhibition of all Kir6.2‐F333I/SUR channel types was reduced, although SUR1‐containing channels were reduced more than SUR2‐containing channels. These results suggest F333 is involved in differential coupling of Kir6.2 to SUR1 and SUR2. When Mg2+ was present, ATP blocked SUR2A channels but activated SUR2B and SUR1 channels. Activation by MgGDP (or MgADP) was similar for wild‐type and mutant channels and was independent of SUR. This indicates Mg‐nucleotide binding to SUR and the transduction of binding into opening of the Kir6.2 pore are unaffected by the mutation. The data further suggest that MgATP hydrolysis by the nucleotide‐binding domains of SUR1 and SUR2B, but not SUR2A, is enhanced by the F333I mutation in Kir6.2. Taken together, our data suggest the region of the C terminus within which F333 lies is involved in more than one type of functional interaction with SUR, and that F333 interacts differentially with SUR1 and SUR2.
Temperature preconditioning of isolated rat hearts – a potent cardioprotective mechanism involving a reduction in oxidative stress and inhibition of the mitochondrial permeability transition pore
Authors: Khaliulin Igor , Clarke Samantha J. , Lin Hua , Parker Joanna , Suleiman M.‐Saadeh , Halestrap Andrew P.
Published: March 2007

We investigate whether temperature preconditioning (TP), induced by short‐term hypothermic perfusion and rewarming, may protect hearts against ischaemic/reperfusion injury like ischaemic preconditioning (IP). Isolated rat hearts were perfused for 40 min, followed by 25 min global ischaemia and 60 min reperfusion (37°C). During pre‐ischaemia, IP hearts underwent three cycles of 2 min global ischaemia and 3 min reperfusion at 37°C, whereas TP hearts received three cycles of 2 min hypothermic perfusion (26°C) interspersed by 3 min normothermic perfusion. Other hearts received a single 6 min hypothermic perfusion (SHP) before ischaemia. Both IP and TP protocols increased levels of high energy phosphates in the pre‐ischaemic heart. During reperfusion, TP improved haemodynamic recovery, decreased arrhythmias and reduced necrotic damage (lactate dehydrogenase release) more than IP or SHP. Measurements of tissue NAD+ levels and calcium‐induced swelling of mitochondria isolated at 3 min reperfusion were consistent with greater inhibition of the mitochondrial permeability transition at reperfusion by TP than IP; this correlated with decreased protein carbonylation, a surrogate marker for oxidative stress. TP increased protein kinase Cɛ (PKCɛ) translocation to the particulate fraction and pretreatment with chelerythrine (PKC inhibitor) blocked the protective effect of TP. TP also increased phosphorylation of AMP‐activated protein kinase (AMPK) after 5 min index ischaemia, but not before ischaemia. Compound C (AMPK inhibitor) partially blocked cardioprotection by TP, suggesting that both PKC and AMPK may mediate the effects of TP. The presence of N‐(2‐mercaptopropionyl) glycine during TP also abolished cardioprotection, indicating an involvement of free radicals in the signalling mechanism.
NHE3 inhibition by cAMP and Ca2+ is abolished in PDZ‐domain protein PDZK1‐deficient murine enterocytes
Authors: Cinar Ayhan , Chen Mingmin , Riederer Brigitte , Bachmann Oliver , Wiemann Martin , Manns Michael , Kocher Olivier , Seidler Ursula
Published: March 2007

The PDZ‐binding protein PDZK1 (NHERF3/CAP70/PDZ‐dc‐1) in vitro binds to NHE3, but its role in the regulation of NHE3 activity in native enterocytes is unknown. This study was undertaken to understand the physiological role of PDZK1 in regulating NHE3 activity in native murine colonic enterocytes. NHE3 transport rates were assessed fluorometrically in BCECF‐loaded colonic crypts in the NHE3‐expressing cryptal openings by measuring acid‐activated, Na+‐dependent, Hoe 642‐insensitive proton efflux rates. NHE3 mRNA expression levels and NHE3 total enterocyte and brush border membrane (BBM) protein abundance were determined by quantitative PCR and Western analysis and immunohistochemistry. In pdzk1−/− colonic surface cells, acid‐activated NHE3 transport rates were strongly reduced, and the inhibitory effect of forskolin and ionomcyin was virtually abolished. Hyperosmolarity, on the other hand, still had an inhibitory effect. In addition, the NHE3‐selective inhibitor S1611 inhibited acid‐activated NHE3 activity in pdzk1−/− and +/+ mice, suggesting that functional NHE3 is present in pdzk1‐deficient colonocytes. NHE1 and NHE2 activity was not altered in pdzk1−/− colonic crypts. Immunohistochemistry revealed apical NHE3 staining in pdzk1−/− and +/+ proximal colon, and Western blot analysis revealed no difference in NHE3 abundance in colonic enterocyte homogenate as well as brush border membrane. Lack of the PDZ‐adaptor protein PDZK1 in murine proximal colonic enterocytes does not influence NHE3 abundance or targeting to the apical membrane, but abolishes NHE3 regulation by cAMPergic and Ca2+ ‐dependent pathways. It leaves NHE3 inhibition by hyperosmolarity intact, suggesting an important and selective role for PDZK1 in the agonist‐mediated regulation of intestinal NHE3 activity.
Imaging and manipulating phosphoinositides in living cells
Authors: Balla Tamas
Published: March 2007

Phosphoinositides are minor phospholipid constituents of virtually every biological membrane yet they play fundamental roles in controlling membrane‐bound signalling events. Phosphoinositides are produced from phosphatidylinositol (PtdIns) by phosphorylation of one or more of three positions (3, 4 and 5) of the inositol headgroup located at the membrane cytoplasmic interface by distinct families of inositol lipid kinases. Intriguingly, many of the kinase reactions are catalysed by more than one form of the kinases even in simple organisms and these enzymes often assume non‐redundant functions. A similar diversity is seen with inositide phosphatases, the enzymes that dephosphorylate phosphoinositides with a certain degree of specificity and the impairments of which are often linked to human diseases. This degree of multiplicity at the enzyme level together with the universal roles of these lipids in cell regulation assumes that inositol lipids are spatially and functionally restricted in specific membrane compartments. Studying the compartmentalized roles of these lipids at the cellular level represents a major methodological challenge. Over the last 10 years significant progress has been made in creating reagents that can monitor inositol lipid changes in live cells with fluorescence or confocal microscopy. New methods are also being developed to manipulate these lipids in specific membrane compartments in a regulated fashion. This article recalls some historical aspects of inositide research and describes the new methodological advances highlighting their great potential as well as the problems one can encounter with their use.
On the Viscosity and Physical Origin of Stability of Weakly Bound Complexes CdZn, HgZn and HgCd
Authors: Ilčin Michal , Lukeš Vladimír , Laurinc Viliam , Biskupič Stanislav
Published: March 2007

Supermolecular CCSD(T)ab initiocalculations of potential energy curves for the electronic ground states of heteronuclear van der Waals complexes formed from the atoms of IIB group are presented. The physical origin of stability of the studied structures was analyzed by the symmetry-adapted perturbation theory. The magnitude of dispersion term increases with the increase of diatomic mass, but the relative importance of dispersion vs Hartree- Fock induction energies decreases in the order CdZn > HgZn > HgCd. Theoretical calculations of the temperature dependence of the shear viscosity for low-density binary mixtures are in good agreement with the temperature dependences of the shear viscosity obtained from empirical formula.
Financial incentives for antipsychotic depot medication: ethical issues: Table 1
Authors: Claassen Dirk
Published: March 2007

Background:Giving money as a direct incentive for patients in exchange for depot medication has proved beneficial in some clinical cases in assertive outreach (AO). However, ethical concerns around this practice have been raised, and will be analysed in more detail here.

Method:Ethical concern voiced in a survey of all AO teams in England were analysed regarding their content. These were grouped into categories.

Results:53 of 70 team managers mentioned concerns, many of them serious and expressing a negative attitude towards giving money for depot adherence. Four broad categories of ethical concern following Christensen’s concept were distinguished: valid consent and refusal (n = 5), psychiatric paternalism (n = 31), resource allocation (n = 4), organisational relationships (n = 2), with a residual category others and unspecified (n = 11).

Discussion:The main concerns identified are discussed on the background of existing ethical theories in healthcare and the specific problems of community mental health and AO. Points for practice are derived from this discussion. A way forward is outlined that includes informed consent and an operational policy in the use of incentives, further randomised controlled trials and qualitative studies, and continuing discussions with all stakeholders, especially service users.
“Do-not-resuscitate” orders in patients with cancer at a children’s hospital in Taiwan
Authors: Jaing Tang-Her , Tsay Pei-Kwei , Fang En-Chen , Yang Shu-Ho , Chen Shih-Hsiang , Yang Chao-Ping , Hung Iou-Jih
Published: March 2007

Objectives:To quantify the use of do-not-resuscitate (DNR) orders in a tertiary-care children’s hospital and to characterise the circumstances in which such orders are written.

Design:Retrospective study conducted in a 500-bed children’s hospital in Taiwan.

Patients:The course of 101 patients who died between January 2002 and December 2005 was reviewed. The following data were collected: age at death, gender, disease and its status, place of death and survival. There were 59 males and 42 females with a median age of 103 months (range 1–263 months). 50 children had leukaemias, and 51 had malignancies other than leukaemia. The t test and the χ2test were applied as appropriate.

Results:The study found that 44% of patient deaths occurred in the paediatric oncology ward; 29% of patient deaths occurred in the intensive care unit; and 28% of patients died in their home or at another hospital. Other findings included the following: 46 of 101 (46%) patients died after attempted cardiopulmonary resuscitation and 55 (54%) died with a DNR order in effect. The mean age at death was 9.8 years in both groups with or without DNR orders.

Conclusions:From the study of patient deaths in this tertiary-care children’s hospital, it was concluded that an explicit DNR order is now the rule rather than the exception, with more DNR orders being written for patients who have been ill longer, who have solid tumours, who are not in remission and who are in the ward.
Women’s smoking history prior to entering the US Navy: a prospective predictor of performance
Authors: Conway Terry L , Woodruff Susan I , Hervig Linda K
Published: March 2007

Objective:To examine whether women’s tobacco use prior to entering the US Navy is predictive of subsequent career performance. A priori predictions were that smoking at entry into the Navy would be related to early attrition, poorer job performance, more disciplinary problems and lower likelihood of re-enlistment.

Methods:A prospective cohort analysis of 5487 women entering the US Navy between March 1996 and March 1997 was conducted. Navy attrition/retention and career performance measures, such as time in service, early attrition, type of discharge, misconduct, number of promotions, demotions and unauthorised absences, highest paygrade achieved, and re-enlistment were examined.

Results:Compared with never smokers, daily smokers at entry into the US Navy had subsequent career outcomes consistently indicating poorer job performance (eg, early attrition prior to serving a full-term enlistment, more likely to have a less-than-honourable discharge, more demotions and desertions, lower achieved paygrade and less likely to re-enlist). Other types of smokers consistently fell between never and daily smokers on career outcome measures.

Conclusions:For women entering the US Navy, being a daily smoker is a prospective predictor of poorer performance in the Navy. Future research should evaluate the effectiveness of cessation intervention with smoker-enlistees prior to their entering the Navy, to assess the impact on subsequent career outcomes.
The California Tobacco Control Program’s effect on adult smokers: (1) Smoking cessation
Authors: Messer Karen , Pierce John P , Zhu Shu-Hong , Hartman Anne M , Al-Delaimy Wael K , Trinidad Dennis R , Gilpin Elizabeth A
Published: March 2007

Objectives:To estimate national population trends in long-term smoking cessation by age group and to compare cessation rates in California (CA) with those of two comparison groups of states.

Setting:Retrospective smoking history of a population sample from the US: from CA, with a comprehensive tobacco-control programme since 1989 with the goal of denormalising tobacco use; from New York and New Jersey (NY & NJ), with similar high cigarette prices but no comprehensive programme; and from the tobacco-growing states (TGS), with low cigarette prices, no tobacco-control programme and social norms relatively supportive of tobacco use.

Participants:Respondents to the Current Population Survey–Tobacco Use Supplements (1992–2002; n = 57 918 non-Hispanic white ever-smokers).

Main outcome measures:The proportion of recent ever-smokers attaining long-term abstinence (quit ⩾1 year) and the successful-quit ratio (the proportion of all ever-smokers abstinent ⩾1 year).

Results:Nationally, long-term cessation rates increased by 25% from the 1980s to the 1990s, averaging 3.4% per year in the 1990s. Cessation increased for all age groups, and by >40% (p<0.001) among smokers aged 20–34 years. For smokers aged <50 years, higher cigarette prices were associated with higher quitting rates. For smokers aged <35 years, quitting rates in CA were higher than in either comparison group (p<0.05). Half of the ever-smokers had quit smoking by age 44 years in CA, 47 years in NY & NJ, and by age 54 years in TGS.

Conclusion:Successful smoking cessation increased by 25% during the1990s in the US. Comprehensive tobacco-control programmes were associated with greater cessation success than were with high cigarette prices alone, although both effects were limited to younger adults.
The California Tobacco Control Program’s effect on adult smokers: (2) Daily cigarette consumption levels
Authors: Al-Delaimy Wael K , Pierce John P , Messer Karen , White Martha M , Trinidad Dennis R , Gilpin Elizabeth A
Published: March 2007

Objective:To investigate the association of the California Comprehensive Tobacco Control Program with self-reported population trends of cigarette consumption during 1992–2002.

Setting and Participants:Participants were non-Hispanic white daily smokers (aged 20–64 years, n = 24 317) from the Tobacco Use Supplements to the Current Population Survey (1992–2002). We compared age-specific trends in consumption among daily smokers in three groups of states with differing tobacco control initiatives: California (CA; high cigarette price/comprehensive programme), New York and New Jersey (high cigarette price/no comprehensive programme), and tobacco-growing states (TGS; low cigarette price/no comprehensive programme).

Results:There was a general decline in cigarette consumption across all age groups in each category of states between 1992 and 2002, except the oldest age group in the TGS. The largest annual decline in the average number of cigarettes per day was observed among daily smokers in CA who were aged ⩾35 years (−0.41 cigarettes/day/year (95% CI −0.52 to −0.3)). This rate was significantly higher than the −0.22 cigarettes/day/year (95% CI −0.3 to −0.16; p<0.02) observed in same-age daily smokers from New York and New Jersey, and significantly higher than the rate in same-age daily smokers from the TGS (−0.15 cigarettes/day/year (95% CI −0.22 to −0.08; p<0.002)). There were no significant differences across state groups in the decline observed in daily smokers aged 20–34 years. In 2002, only 12% of daily smokers in CA smoked more than a pack per day, which was significantly lower than the 17% in New York and New Jersey, which again was significantly lower than the 25% in the TGS.

Conclusions:The California Tobacco Control Program was associated with significant declines in cigarette consumption among daily smokers aged ⩾35 years of age, which in turn should lead to declines in tobacco-related health effects. The decline in consumption among young adult smokers was a national trend.
The California Tobacco Control Program’s effect on adult smokers: (3) Similar effects for African Americans across states
Authors: Trinidad Dennis R , Messer Karen , Gilpin Elizabeth A , Al-Delaimy Wael K , White Martha M , Pierce John P
Published: March 2007

Objective:To compare trends in African-American (AA) and non-Hispanic white (NHW) smoking between states categorised as having three different levels of tobacco control practice in the 1990s.

Setting and participants:Analysis of 1992–3 to 2001–2 Tobacco Use Supplements to the Current Population Survey for differences in adult (20–64 years) daily smoking prevalence for AAs and NHWs across states: California (CA; high cigarette price/comprehensive programme), New York (NY) and New Jersey (NJ; high cigarette price/no comprehensive programme), and tobacco growing states (TGS; low cigarette price/no comprehensive programme).

Results:From 1992–3 to 2001–2, there were large declines in AA smoking across states (2.7–3.8% decrease/year, adjusted for age, income, education, gender; p<0.05). Adjusted NHW smoking prevalence declined significantly only in CA. AA prevalence declined significantly and did not differ across state groups. In all years, in all state groups, adjusted prevalence was either not significantly different or was lower for AAs than for NHWs. More recent cohorts of AAs appeared to have taken up smoking at lower rates than older cohorts.

Conclusion:There were uniformly large declines in AA smoking from 1992–3 to 2001–2 across states, independent of type of tobacco control strategy. Further research is needed into factors associated with smoking declines among AAs.
Secondhand smoke levels in Scottish pubs: the effect of smoke-free legislation
Authors: Semple Sean , Creely Karen S , Naji Audrey , Miller Brian G , Ayres Jon G
Published: March 2007

Objective:To compare levels of particulate matter, as a marker of secondhand smoke (SHS) levels, in pubs before and 2 months after the implementation of Scottish legislation to prohibit smoking in substantially enclosed public places.

Design:Comparison of SHS levels before and after the legislation in a random selection of 41 pubs in 2 Scottish cities.

Methods:Fine particulate matter <2.5 μm in diameter (PM2.5) was measured discreetly for 30 min in each bar on 1 or 2 visits in the 8 weeks preceding the starting date of the Smoking, Health and Social Care (Scotland) Act 2005 and then again 2 months after the ban. Repeat visits were undertaken on the same day of the week and at approximately the same time of the day.

Results:PM2.5levels before the introduction of the legislation averaged 246 μg/m3(range 8–902 μg/m3). The average level reduced to 20 μg/m3(range 6–104 μg/m3) in the period after the ban. Levels of SHS were reduced in all 53 post-ban visits, with the average reduction being 86% (range 12–99%). PM2.5concentrations in most pubs post-ban were comparable to the outside ambient air PM2.5level.

Conclusions:This study has produced the largest dataset of pre- and post-ban SHS levels in pubs of all worldwide smoke-free legislations introduced to date. Our results show that compliance with the Smoking, Health and Social Care (Scotland) Act 2005 has been high and this has led to a marked reduction in SHS concentrations in Scottish pubs, thereby reducing both the occupational exposure of workers in the hospitality sector and that of non-smoking patrons.
British American Tobacco’s tactics during China’s accession to the World Trade Organization
Authors: Zhong Fei , Yano Eiji
Published: March 2007

Background:China entered the World Trade Organization (WTO) in 2001 after years of negotiations. As a WTO member, China had to reduce tariffs on imported cigarettes and remove non-tariff barriers to allow foreign cigarettes to be more competitive in the Chinese market. Among foreign tobacco companies, British American Tobacco (BAT) was the most active lobbyist during China’s WTO negotiations.

Objective:To review and analyse BAT’s tactics and activities relating to China’s entry into the WTO.

Methods:Internal tobacco industry documents were reviewed and are featured here. Industry documents were searched mainly on the website of BAT’s Guildford Depository and other documents’ websites. 528 documents were evaluated and 142 were determined to be relevant to China’s entry into the WTO.

Results:BAT was extremely active during the progress of China’s entry into the WTO. The company focused its lobbying efforts on two main players in the negotiations: the European Union (EU) and the US. Because of the negative moral and health issues related to tobacco, BAT did not seek public support from officials associated with the WTO negotiations. Instead, BAT lobbyists suggested that officials protect the interests of BAT by presenting the company’s needs as similar to those of all European companies. During the negotiation process, BAT officials repeatedly spoke favourably of China’s accession into the WTO, with the aim of presenting BAT as a facilitator in this process and of gaining preferential treatment from their Chinese competitor.

Conclusions:BAT’s activities clearly suggest that tobacco companies place their own interests above public health interests. Today, China struggles with issues of tobacco control that are aggravated by the aggressive practices of transnational tobacco companies, tobacco-tariff reductions and the huge number of smokers. For the tobacco-control movement to progress in China, health advocates must understand how foreign tobacco companies have undermined anti-tobacco activities by taking advantage of trade liberalisation policies. China should attach importance to public health and comprehensive tobacco-control policies and guarantee strong protection measures from national and international tobacco interests supported by international trade agreements.
THE MODIFIED CHAPLYGIN GAS AS A UNIFIED DARK SECTOR MODEL
Authors: WU YABO , LI SONG , LU JIANBO , YANG XIUYI
Published: March 2007

A modified Chaplygin gas (MCG) model of unifying dark energy and dark matter is considered in this paper. Concretely, the evolution of such a unified dark sector model is studied and the statefinder diagnostic to the MCG model is performed in our model. By analysis, it is shown that the state parameter of dark energy can cross the so-called phantom divide ω = -1, the behavior of MCG will be like ΛCDM in the future and therefore our universe will not end up with Big Rip in the future. In addition, we plot the evolution trajectory of the MCG model in the statefinder parameter r–s plane and show the discrimination between this scenario and other dark energy models.
PLANCK FLUCTUATIONS, MEASUREMENT UNCERTAINTIES AND THE HOLOGRAPHIC PRINCIPLE
Authors: REQUARDT MANFRED
Published: March 2007

Starting from a critical analysis of recently reported surprisingly large uncertainties in length and position measurements deduced within the framework of quantum gravity, we embark on an investigation both of the correlation structure of Planck scale fluctuations and the role the holographic hypothesis is possibly playing in this context. While we prove the logical independence of the fluctuation results and the holographic hypothesis (in contrast to some recent statements in that direction) we show that by combining these two topics one can draw quite strong and interesting conclusions about the details of the fluctuation structure and the microscopic dynamics on the Planck scale. We further argue that these findings point to a possibly new and generalized form of quantum statistical mechanics of strongly (anti)correlated systems of degrees of freedom in this fundamental regime.
SIMILARITIES BETWEEN CLASSICAL TIME-LIKE GEODESICS IN A NAKED REISSNER–NORDSTRÖM SINGULARITY BACKGROUND AND THE BEHAVIOR OF ELECTRONS IN QUANTUM THEORY
Authors: QADIR ASGHAR , SIDDIQUI AZAD A.
Published: March 2007

A study of classical time-like geodesics in a naked Reissner–Nordström singularity background is presented. Regarding the electron as naked a singularity, the size of the clothed singularity turns out to be classical electro-magnetic radius of the electron, to an observer falling freely from infinity, initially at rest. The size shrinks for an observer falling freely from infinity, with a positive initial velocity. For geodetic parameters corresponding to negative energy there are trapped geodesics. The similarity of this picture with that arising in quantum theory is discussed.
NECESSARY AND SUFFICIENT CONDITION FOR HYDROSTATIC EQUILIBRIUM IN GENERAL RELATIVITY
Authors: NEGI P. S.
Published: March 2007

We present explicit examples to show that the "compatibility criterion" (recently obtained by us toward providing equilibrium configurations compatible with the structure of general relativity) which states that for a given value of σ[≡ (P0/E0) ≡ the ratio of central pressure to central energy-density], the compactness ratio u[≡ (M/R), where M is the total mass and R is the radius of the configuration] of any static configuration cannot exceed the compactness ratio, uh, of the homogeneous density sphere (i.e., u ≤ uh) is capable of providing a necessary and sufficient condition for any regular configuration to be compatible with the state of hydrostatic equilibrium. This conclusion is drawn on the basis of the finding that the M–R relation gives the necessary and sufficient condition for dynamical stability of equilibrium configurations only when the compatibility criterion for these configurations is appropriately satisfied. In this regard, we construct an appropriate sequence composed of core-envelope models on the basis of compatibility criterion such that each member of this sequence satisfies the extreme case of causality condition v = c = 1 at the center. The maximum stable value of u ≃ 0.3389 (which occurs for the model corresponding to the maximum value of mass in the mass–radius relation) and the corresponding central value of the local adiabatic index, (Γ1)0 ≃ 2.5911, of this model are found fully consistent with those of the corresponding absolute values, u max ≤ 0.3406 and (Γ1)0 ≤ 2.5946, which impose strong constraints on these parameters of such models. In addition to this example, we also study dynamical stability of pure adiabatic polytropic configurations on the basis of variational method for the choice of the "trial function," ξ = reν/4, as well as the mass–central density relation, since the compatibility criterion is appropriately satisfied for these models. The results of this example provide additional proof in favor of the statement regarding compatibility criterion mentioned above. Together with other results, this study also confirms the previous claim that just the choice of the "trial function," ξ = reν/4, is capable of providing the necessary and sufficient condition for dynamical stability of a mass on the basis of variational method. Obviously, the upper bound on the compactness ratio of neutron stars, u ≅ 0.3389, which belongs to two-density model studied here, turns out to be much stronger than the corresponding "absolute" upper bound mentioned in the literature.
RESONANT FREQUENCIES OF CHARGED SCALAR AND DIRAC FIELDS IN KERR–NEWMAN BLACK-HOLE SPACE–TIME
Authors: JING JILIANG , PAN QIYUAN , HE XI
Published: March 2007

The resonant frequencies of the charged scalar and Dirac fields in the near extremal Kerr–Newman black hole are studied. It is found that the expressions of the resonant frequencies for the charged scalar and Dirac fields with purely real δ are different because the parameters qs are different and the imaginary part has opposing symbol for the two fields. It is also shown that the long-lived resonant frequencies depend on the angular quantum numbers l and m.
Overexpression ofKrüppel-like factor 5 in esophageal epithelia in vivo leads to increased proliferation in basal but not suprabasal cells
Authors: Goldstein Bree G. , Chao Hann-Hsiang , Yang Yizeng , Yermolina Yuliya A. , Tobias John W. , Katz Jonathan P.
Published: March 2007

Krüppel-like factor 5 ( Klf5; also called IKLF or BTEB2), a zinc-finger transcription factor with proproliferative and transforming properties in vitro, is expressed in proliferating cells of gastrointestinal tract epithelia, including in basal cells of the esophagus. Thus, Klf5 is an excellent candidate to regulate esophageal epithelial proliferation in vivo. Nonetheless, the function of Klf5 in esophageal epithelial homeostasis and tumorigenesis in vivo has not previously been determined. Here, we used the ED- L2 promoter of the Epstein-Barr virus to express Klf5 throughout esophageal epithelia. ED-L2/ Klf5 transgenic mice were born at the appropriate Mendelian ratio, survived to at least 1 yr of age, and showed no evidence of esophageal dysplasia or cancer. Staining for bromodeoxyuridine (BrdU) demonstrated increased proliferation in the basal layer of ED-L2/ Klf5 mice, but no proliferation was seen in suprabasal cells, despite ectopic expression of Klf5 in these cells. Notably, expression of the KLF family member Klf4, which binds the same DNA sequences as Klf5 and which inhibits proliferation and promotes differentiation, was not altered in ED-L2/ Klf5 transgenic mice. In primary esophageal keratinocytes that overexpressed Klf5, expression of Klf4 still inhibited proliferation and promoted differentiation, providing a possible mechanism for the persistence of keratinocyte differentiation in ED-L2/ Klf5 mice. To identify additional targets for Klf5 in esophageal epithelia, we performed functional genomic analyses and identified a total of 15 differentially expressed genes. In summary, while Klf5 positively regulates proliferation in basal cells, it is not sufficient to maintain proliferation in the esophageal epithelium.
Interleukin-6 inhibits growth hormone-mediated gene expression in hepatocytes
Authors: Ahmed Tamer A. , Buzzelli Mark D. , Lang Charles H. , Capen John B. , Shumate Margaret L. , Navaratnarajah Maithili , Nagarajan Murali , Cooney Robert N.
Published: March 2007

During systemic inflammation, the liver becomes unresponsive to growth hormone (GH), resulting in decreased plasma insulin-like growth factor-I (IGF-I) with concomitant reductions in lean body mass. Transgenic mice that overexpress IL-6 also demonstrate impaired growth and decreased IGF-I. To determine whether IL-6 directly inhibits GH-inducible gene expression, CWSV-1 hepatocytes were incubated with IL-6 (10 ng/ml), then stimulated with recombinant human GH (500 ng/ml, 18 h). The increase in IGF-I and serine protease inhibitor 2.1 (Spi 2.1) mRNA in GH-treated cells was inhibited by treatment with IL-6 for 24 h. To investigate potential mechanisms, we examined the effects of IL-6 on GH receptor (GHR) expression and GH signaling via the JAK/signal transducer and activator of transcription (STAT) and MAP kinase pathways. Incubation of cells with IL-6 (10 ng/ml, 24 h) had no effect on GHR abundance or signaling proteins JAK2, STAT5b, and ERK1/2. Although GH transiently increased (2- to 5-fold) the tyrosine phosphorylation of GHR, JAK2, STAT5b, and ERK1/2, IL-6 did not alter these phosphorylation events. However, nuclear protein from IL-6-treated cells demonstrated reduced STAT5 DNA binding (by EMSA) at 15 min (−20%) and 60 min (−43%) after GH stimulation. To determine whether IL-6 inhibits GH-inducible promoter activity, CWSV-1 cells were transfected with Spi 2.1 or prolactin receptor promoter luciferase vectors, incubated with or without IL-6, then stimulated with GH. The induction of both Spi 2.1 (7.5-fold) and prolactin receptor (4-fold) promoter activity by GH was inhibited by IL-6. In summary, IL-6 mediates hepatic GH resistance by a time-dependent inhibition of GH-inducible promoter activity that is associated with reductions in STAT5 DNA binding.
Elastin-insufficient mice show normal cardiovascular remodeling in 2K1C hypertension despite higher baseline pressure and unique cardiovascular architecture
Authors: Wagenseil Jessica E. , Knutsen Russell H. , Li Dean Y. , Mecham Robert P.
Published: March 2007

Mice heterozygous for the elastin gene (ELN+/−) show unique cardiovascular properties, including increased blood pressure and smaller, thinner arteries with an increased number of lamellar units. Some of these properties are also observed in humans with supravalvular aortic stenosis, a disease caused by functional heterozygosity of the elastin gene. The arterial geometry in ELN+/− mice is contrary to the increased thickness that would be expected in an animal demonstrating hypertensive remodeling. To determine whether this is due to a decreased capability for cardiovascular remodeling or to a novel adaptation of the ELN+/− cardiovascular system, we increased blood pressure in adult ELN+/+ and ELN+/− mice using the two-kidney, one-clip Goldblatt model of hypertension. Successfully clipped mice have a systolic pressure increase of at least 15 mmHg over sham-operated animals. ELN+/+ and ELN+/−-clipped mice show significant increases over sham-operated mice in cardiac weight, arterial thickness, and arterial cross-sectional area with no changes in lamellar number. There are no significant differences in most mechanical properties with clipping in either genotype. These results indicate that ELN+/+ and ELN+/− hearts and arteries remodel similarly in response to adult induced hypertension. Therefore, the cardiovascular properties of ELN+/− mice are likely due to developmental remodeling in response to altered hemodynamics and reduced elastin levels.
Cluster analysis tests the importance of myogenic gene expression during myofiber hypertrophy in humans
Authors: Bamman Marcas M. , Petrella John K. , Kim Jeong-su , Mayhew David L. , Cross James M.
Published: March 2007

We applied K-means cluster analysis to test the hypothesis that muscle-specific factors known to modulate protein synthesis and satellite cell activity would be differentially expressed during progressive resistance training (PRT, 16 wk) in 66 human subjects experiencing extreme, modest, and failed myofiber hypertrophy. Muscle mRNA expression of IGF-I isoform Ea (IGF-IEa), mechanogrowth factor (MGF, IGF-IEc), myogenin, and MyoD were assessed in muscle biopsies collected at baseline (T1) and 24 h after the first (T2) and last (T3) loading bouts from previously untrained subjects clustered as extreme responders (Xtr, n = 17), modest responders (Mod, n = 32), and nonresponders (Non, n = 17) based on mean myofiber hypertrophy. Myofiber growth averaged 2,475 μm2 in Xtr, 1,111 μm2 in Mod, and −16 μm2 in Non. Main training effects revealed increases in all transcripts (46–83%, P < 0.005). For the entire cohort, IGF-IEa, MGF, and myogenin mRNAs were upregulated by T2 ( P < 0.05), while MyoD did not increase significantly until T3 ( P < 0.001). Within clusters, MGF and myogenin upregulation was robust in Xtr (126% and 65%) and Mod (73% and 41%) vs. no changes in Non. While significant in all clusters by T3, IGF-IEa increased most in Xtr (105%) and least in Non (44%). Although MyoD expression increased overall, no changes within clusters were detected. We reveal for the first time that MGF and myogenin transcripts are differentially expressed in subjects experiencing varying degrees of PRT-mediated myofiber hypertrophy. The data strongly suggest the load-mediated induction of these genes may initiate important actions necessary to promote myofiber growth during PRT, while the role of MyoD is less clear.
Altered Ca2+handling and myofilament desensitization underlie cardiomyocyte performance in normothermic and hyperthermic heat-acclimated rat hearts
Authors: Cohen Omer , Kanana Hifa , Zoizner Ronen , Gross Chaya , Meiri Uri , Stern Michael D. , Gerstenblith Gary , Horowitz Michal
Published: March 2007

Heat acclimation (AC) improves cardiac mechanical and metabolic performance. Using cardiomyocytes and isolated hearts from 30-day and 2-day acclimated rats (AC and AC-2d, 34°C), we characterized cellular contractile mechanisms under normothermic (37°C) and hyperthermic (39–42°C) conditions. To determine contractile responses, Ca2+transients (Ca2+T), sarcoplasmic reticulum (SR) Ca2+pool size (fura-2/indo-1 fluorescence), force generation [amplitude systolic motion (ASM)], L-type Ca2+channels [dihydropyridine receptor (DHPR)], ryanodine receptors (RyRs), and total (PLBt) and phosphorylated phospholamban [serine phosphorylated (PLBs) and theonine phosphorylated (PLBtr)] proteins and transcripts were measured (Western blot, RT-PCR). Cardiac mechanical performance was measured using a Langendorff system. We demonstrated that AC and AC-2d increased Ca2+T amplitude (148% and 147%, respectively) and twitch force (180% and 130%, respectively) and desensitized myofilaments, as indicated by a rightward shift in the ASM-Ca2+relationships, despite no change in SR Ca2+pool size. Hence, generation of higher Ca2+T underlies greater force development in AC and AC-2d myocytes. In isolated hearts, ryanodine administration eliminated differences between AC and control (C) hearts, implying an important role for RyRs in that acclimation phase. Increased expression of DHPR and RyRs, and decreased PLBs/PLBt in AC hearts only, suggest that different pathways increase force generation in the AC-2d vs. AC myocytes. At basal beating rates, hyperthermia (39–41°C) enhanced pressure generation in AC hearts. C hearts failed to restitute pressure beyond 39°C. Increased beating frequency produced negative inotropic response. In C cardiomyocytes, hyperthermia elevated basal cytosolic Ca2+and tension, Ca2+T, and ASM. AC myocytes enhanced Ca2+T but showed myofilament desensitization, suggesting its involvement in cardiac protection against hyperthermia. Collectively, both Ca2+turnover and myofilament responsiveness are important adaptive acclimatory targets during normothermic and hyperthermic conditions.
Trans-Obturator Tape for Incontinence: A 3-Year Follow-Up
Authors: Al-Singary W. , Shergill I.S. , Allen S.E. , John J.A. , Arya M. , Patel H.R.H.
Published: March 2007

Aim: To assess operative and functional outcomes, including morbidity, after using the trans-obturator tape for stress incontinence. Patients and Methods: The first 24 consecutive patients undergoing trans-obturator tape insertion in a single centre were included in this retrospective study. All patients were female with a mean age of 63 (range 40–83) years. Fifteen patients (62.5%) suffered from pure stress incontinence, and 9 patients (37.5%) had mixed incontinence. Of the latter, 2 patients also had nocturnal enuresis. Each patient was followed up for between 3 and 12 months postoperatively and again at 36 months. The patients were assessed by clinical examination, ultrasound for residual urinary volume, and subjective satisfaction which was assessed at 3 and 12 months. At 36 months, all patients completed a validated incontinence questionnaire (International Consultation on Incontinence Questionnaire: ICIQ) which assessed female lower urinary tract symptoms and their impact on the quality of life. Results: All operations were performed under epidural anaesthesia in day surgery, and the mean operative time was 20 (range 15–38) min. Nineteen patients (79.2%) showed significant improvement postoperatively, with 16 of those (66.6%) being completely cured of their incontinence. The remaining 5 patients (20.8%) were considered to have had failed procedures. There were no vascular, bladder, or urethral injuries. One patient had perforation of the vaginal fornix, and 3 patients developed vaginal erosion. Conclusions: The trans-obturator tape is a safe and effective treatment for stress incontinence and has a low morbidity after a 3-year follow-up period; however, it should only be performed by clinicians with the relevant surgical expertise and experience in treating female incontinence.
Is Ultrasound of the Retroperitoneum a Valuable Staging Method in Selecting Testicular Cancer Patients for Primary Retroperitoneal Lymph Node Dissection?
Authors: Mezvrishvili Zaza , Tchanturaia Zaza , Toidze Tengiz , Turmanidze Nino , Kekelidze Maka , Managadze Laurent
Published: March 2007

Objective: In nonseminomatous testicular cancer patients with normal serum tumor markers and no distant metastasis, postorchiectomy surgery is a valid treatment option if the disease extension into the retroperitoneum is not advanced. We assessed the ability of ultrasound (US) to exclude the presence of bulky retroperitoneal disease. Materials and Methods: One hundred and forty testicular cancer patients underwent US and computed tomography (CT) of the retroperitoneum. US results were analyzed using three cutoffs: 5 cm (conventional staging), 3 cm (based on the minimal sonographical dimension of actual bulky disease) and 0 cm (‘clean retroperitoneum’ or any detectable nodes), and were compared with CT data using the 5-cm cutoff (‘gold standard’). Results: The sensitivity, specificity, overall accuracy, positive and negative predictive values of US in detecting of bulky retroperitoneum for the 5-cm cutoff were 83, 96, 93, 88 and 94%, for the 3-cm cutoff 100, 91, 94, 80 and 100%, and for the 0-cm cutoff 100, 66, 74, 49 and 100%, respectively. Conclusions: In stage I and IIA/B marker-negative nonseminomas if the treatment strategy is surgery, US may facilitate the selection process; the report of a clean retroperitoneum safely excludes the presence of bulky disease and may be an indication for lymphadenectomy, although in case of positive findings a CT should be performed.
Citrate in Expressed Prostatic Secretions Has the Feasibility to Be Used as a Useful Indicator for the Diagnosis of Category IIIB Prostatitis
Authors: Chen Jun , Xu Zhishun , Zhao Haifeng , Jiang Xianzhou
Published: March 2007

Introduction: Normal human prostatic secretion is remarkably rich in citrate (EPS-citrate). Prostate inflammation will result in reduction of EPS-citrate level. So EPS-citrate was determined to investigate whether EPS-citrate level was also decreased in category IIIB prostatitis and whether it is feasible for EPS-citrate to be used as a diagnostic marker for category IIIB prostatitis. Materials and Methods: 21 category II outpatients, 25 category IIIA outpatients, 25 category IIIB outpatients and 21 normal controls without any prostatic diseases were included. All category II, IIIA and IIIB outpatients had not received any management. The EPS-citrate was determined by high-performance liquid chromatography. Results: The mean EPS-citrate values were 3.32 ± 0.79, 3.41 ± 0.88, 4.37 ± 0.77 and 8.55 ± 1.20 mg/ml in groups II, IIIA, IIIB and normal controls, respectively. Compared to normal controls, the EPS-citrate levels were significantly decreased in category II, IIIA and IIIB patients. Furthermore, there was no overlap of EPS-citrate values between category IIIA and IIIB patients and the normal control group. Conclusions: The EPS-citrate level is decreased in category IIIB prostatitis and it is feasible for EPS-citrate to be used as a useful diagnostic indicator for category IIIB prostatitis.
Adult Male Circumcision Outcomes: Experience in a Developing Country Setting
Authors: Krieger John N. , Bailey Robert C. , Opeya John C. , Ayieko Benard O. , Opiyo Felix A. , Omondi Dickens , Agot Kawango , Parker Corette , Ndinya-Achola J.O. , Moses Stephen
Published: March 2007

Introduction: We examined male circumcision outcomes among young adults in an African setting. Materials and Methods: Participants were healthy, sexually active, uncircumcised, HIV-seronegative males aged 18–24 years. The main outcomes measured included complications, healing, satisfaction and resumption of activities. Results: Of 1,475 procedures, 26 (1.8%) were associated with 27 adverse events, most commonly wound disruption/delayed healing (0.6%), wound infection (0.4%), and bleeding (0.3%). Adverse events per clinician averaged 3.8 and 2.1% for procedures 1–100 and 101–200, respectively, and <1% for procedures 201–300, 301–400 and >400, respectively (p < 0.001). Participants resumed normal general activities after a median of 1 postoperative day and 93% with regular employment resumed working within 1 week. After 30 days, 99% of participants reported being very satisfied. After 90 days, 65% reported having had sex, 45% reported that their partners had expressed an opinion, 92% of whom were very satisfied with the outcome. Conclusions: Safe and acceptable adult male circumcision services can be delivered in developing country settings.
Value of Urinary Flow Patterns in the Follow-Up of Children Who Underwent Snodgrass Operation
Authors: Kaya Cevdet , Kucuk Eyup , İlktac Abdullah , Ozturk Metin , Karaman M. Ihsan
Published: March 2007

The urinary flow patterns and the Toguri nomogram were compared in the intermediate functional results of the tubularized-incised plate urethroplasty (TIPU) to repair distal and midpenile hypospadias by using uroflowmetry. 28 children who were toilet trained, were able to void volitionally, and had no fistulas following hypospadias repair were eligible for the study. The study did not include children who had persistent fistula, meatal stenosis or urethral stricture, and did not return for follow-up. The mean age was 8.4 years and the mean follow-up period was 18 months. The urinary flow pattern, maximum (Qmax) and average flow rate (Qave) were measured; the results were expressed as percentiles and compared to the Toguri values from normal children. The Qmax and Qave were considered normal if they were in >25th percentile, equivocally obstructed in the 5–25th percentile and obstructed if <5th percentile. The flow pattern was classified as bell ring shape, plateau or intermittent. According to the Toguri nomogram, 22 of 28 patients (78.5%) were considered normal, 4 patients (14.2%) as equivocally obstructed, and 2 patients (7.1%) as obstructed group. A normal bell-shaped flow curve was obtained in 23 (82.1%) of the children. 4 patients (14.2%) had a plateau flow pattern. Only 1 of the patients had an intermittent shape flow curve. The flow pattern was normal bell-shaped for all of the patients, except 1, with Qmax above the 25th percentile according to the Toguri nomogram. Of children with Qmax below the 5th percentile, both of them had a plateau flow pattern and were found to have an asymptomatic meatal stenosis, which was improved with urethral dilatation. However, of the 4 patients with Qmax between 5 and 25 percentiles, 2 had a plateau flow pattern and the others had a bell-shaped flow pattern. The flow patterns of the 2 patients determined as obstructive by the Toguri nomogram were plateau-shaped. TIPU provides satisfactory functional results for distal and midpenile hypospadias; uroflowmetry is an important noninvasive tool to evaluate this technique. There are no studies in the literature which only used flow patterns for the evaluation of urination for follow-up after the hypospadias repair. Our study showed that the evaluation of obstruction according to the Toguri nomogram may not be necessary in patients with a normal bell-shaped flow pattern in uroflowmetry.