bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a new venom‐based clotting assay of protein C
Authors: COOPER P. C. , COOPER S. M. , GOODFELLOW K. J. , HICKEY K. P. , KITCHEN S. , MAKRIS M.
Published: August 2007

Congenital protein C deficiency significantly increases the risk of venous thromboembolism, a serious and potentially lethal condition. Protein C levels can be determined by chromogenic, clotting and antigenic assays, each type of assay has differences in specificity and sensitivity to protein C deficiency. In principle, clotting‐based assays of protein C are preferred over chromogenic assays, as they can detect some rare mutations that are missed by the chromogenic assay, however, clotting‐based assays may be prone to inaccuracy because of poor specificity. We have evaluated a new venom‐based clotting assay of protein C, and optimized it for use on Sysmex CA‐1500 analyser. The assay was linear from 0 to 130 U/dl, a normal plasma demonstrated good inter‐assay precision, with a coefficient of variation of 4.8%. The assay compared well with antigenic‐ and venom‐based chromogenic protein C assay in normal individuals, subjects with lupus anticoagulant, and subjects with FV Leiden. Median protein C levels by clotting, chromogenic and antigen for the three subject groups were 108 U/dl, 108 IU/dl and 109 IU/dl for normal subjects, 94 U/dl, 106 IU/dl and 103 IU/dl for subjects with lupus anticoagulant, and 102 U/dl, 104 IU/dl and 100 IU/dl for subjects heterozygous for FV Leiden. Comparing levels of clotting protein C with protein C antigen by ratio (clotting/antigen), the three groups showed small differences that did not quite reach statistical significance, (mean ratios ranged from 0.95 to 1.01, anovaP = 0.0561), the lowest ratio was with the lupus anticoagulant group. Comparing clotting assay with chromogenic assay by ratio (clotting/chromogenic), the three groups did show a statistically significant difference (P = 0.0033) which was due to a difference in mean ratios between normal and lupus anticoagulant groups (ratios 1.00 and 0.91, respectively, P < 0.01). There was no statistical difference in any of the groups when comparing chromogenic protein C with protein C antigen (mean ratios ranged from 1.02 to 1.05, P = 0.3925). In a normal sample, the clotting‐based protein C level was unaffected by increasing FVIII level by up to 1000 IU/dl, using intermediate purity FVIII concentrate. The new assay is considered to be a suitable assay for the routine diagnosis of protein C deficiency.
To Arbitrate or to Advocate?
Authors: Hultman Nathan E.
Published: August 2007

The Honest Broker
. Making Sense of Science in Policy and Politics.
By Roger A. Pielke Jr.
. Cambridge University Press, Cambridge, 2007. 198 pp. Paper, $29.99. ISBN 9780521694810.

Pielke examines the choices and consequences facing scientists who wish to contribute their research findings to policy-making.
Reduced Egg Investment Can Conceal Helper Effects in Cooperatively Breeding Birds
Authors: Russell A. F. , Langmore N. E. , Cockburn A. , Astheimer L. B. , Kilner R. M.
Published: August 2007

Cooperative breeding systems are characterized by nonbreeding helpers that assist breeders in offspring care. However, the benefits to offspring of being fed by parents and helpers in cooperatively breeding birds can be difficult to detect. We offer experimental evidence that helper effects can be obscured by an undocumented maternal tactic. In superb fairy-wrens (
Malurus cyaneus
), mothers breeding in the presence of helpers lay smaller eggs of lower nutritional content that produce lighter chicks, as compared with those laying eggs in the absence of helpers. Helpers compensate fully for such reductions in investment and allow mothers to benefit through increased survival to the next breeding season. We suggest that failure to consider maternal egg-investment strategies can lead to underestimation of the force of selection acting on helping in avian cooperative breeders.
Quality of theHaemophilus influenzaeType b (Hib) Antibody Response Induced by Diphtheria-Tetanus-Acellular Pertussis/Hib Combination Vaccines
Authors: Denoël Philippe A. , Goldblatt David , de Vleeschauwer Isabel , Jacquet Jeanne-Marie , Pichichero Michael E. , Poolman Jan T.
Published: August 2007

It has been repeatedly observed that mixingHaemophilus influenzaetype b (Hib) conjugate vaccines with acellular pertussis-containing vaccines (diphtheria-tetanus-acellular pertussis [DTPa]) resulted in a reduced magnitude of the anti-polyriboseribitolphosphate antibody response compared to that obtained when Hib vaccines were administered separately and not mixed. Nevertheless, the quality and functionality of the immune responses have been shown to be the same. With the purpose of investigating the quality of the anti-Hib immune responses that are elicited under different vaccination regimens, we report here four primary and booster-based pediatric clinical trials in which Hib vaccine was either mixed with DTPa or diphtheria-tetanus-whole-cell pertussis (DTPw)-based vaccines or was coadministered. Our results show that avidity maturation of the antibodies was lower when primary vaccination involved DTPa mixed with Hib compared to when DTPa and Hib were coadministered. No such difference was observed between mixed and separately administered Hib when associated with DTPa-hepatitis B virus-inactivated poliovirus or DTPw-based vaccines. All different combinations and regimens elicited the same opsonophagocytic and bactericidal activity as well as the same ability to protect in a passive infant rat protection assay. The functional activity of mixed DTPa-based and Hib vaccines was similar to that of mixed DTPw-based/Hib combinations. In conclusion, in vitro and in vivo data as well as postmarketing vaccine effectiveness data attest to the ability of DTPa-based/Hib combination vaccines to effectively prevent Hib-induced disease in children.
Persistence of Antibodies Induced by Measles-Mumps-Rubella Vaccine in Children in India
Authors: Raut S. K. , Kulkarni P. S. , Phadke M. A. , Jadhav S. S. , Kapre S. V. , Dhere R. M. , Dhorje S. P. , Godse S. R.
Published: August 2007

Antibody levels in 41 Indian girls were measured 6 years after measles-mumps-rubella (MMR) vaccination. Rates of seropositivity were 88% (measles antibodies), 95% (mumps antibodies), and 100% (rubella antibodies). The MMR vaccine induces long-term immunity in a majority of vaccinees; however, due to the observation of some seronegative vaccinees, the policy of administering a second dose of the MMR vaccine seems appropriate.
Human Papillomavirus (HPV) Genotyping Using Paired Exfoliated Cervicovaginal Cells and Paraffin-Embedded Tissues To Highlight Difficulties in Attributing HPV Types to Specific Lesions
Authors: Gravitt Patti E. , van Doorn Leen Jan , Quint Wim , Schiffman Mark , Hildesheim Allan , Glass Andrew G. , Rush Brenda B. , Hellman Jared , Sherman Mark E. , Burk Robert D. , Wang Sophia S.
Published: August 2007

Defining type-specific human papillomavirus (HPV) infections within cervical tissues is important for understanding the pathogenesis of cervical neoplasia and assessing the effectiveness of prophylactic vaccines with limited type-specific spectra. We compared HPV DNA-testing results from 146 matched exfoliated-cell and formalin-fixed-tissue specimens collected by cervicovaginal lavage (CVL) within 90 days of each other from women with histologically confirmed cervical intraepithelial lesions (CIN). The CVL specimens were HPV typed using a MY09/11 L1 consensus primer PCR method followed by dot blot hybridization. The tissue specimens were HPV typed using an SPF
10
line probe assay HPV detection system. Of the 146 specimen pairs with evidence of CIN in the tissue, 91.8% were positive for one or more HPV types in both the tissue and cellular specimens. Tissue sections were more likely to be HPV negative (
P
< 0.01). Typing directly from tissue sections resolved multiple infections detected in exfoliated cells to a single HPV type in only 46.9% of cases. Combined use of both specimen types to attribute lesions to HPV type 16 (HPV-16) and/or -18 led to 43.1% attributed to HPV-16 and/or -18 by both specimen types and 19.9% attributed to HPV-16 and/or -18 by one, but not both, specimen types. Unambiguous attribution of cervical lesions to a single, specific HPV type remains a difficult proposition. Use of multiple specimen types or the development of highly sensitive and robust in situ hybridization HPV-testing methods to evaluate the certainty of attribution of lesions to HPV types might provide insights in future efforts, including HPV vaccine trials.
Evaluation of the BD ProbeTec ET System for Direct Detection of
Mycobacterium bovis
in Veterinary Specimens
Authors: Bean David C. , Hills Andrea , Ryan Terry , Aitken John
Published: August 2007

We describe the application of the BD ProbeTec ET direct tuberculosis system for the detection of
Mycobacterium bovis
in bovine and cervine lymph node tissues. Compared to traditional culture, the overall sensitivity, specificity, and positive and negative predictive values of the BD ProbeTec were 87, 100, 100, and 87%, respectively.
Pichia farinosa
Bloodstream Infection in a Lymphoma Patient
Authors: Adler A. , Hidalgo-Grass C. , Boekhout T. , Theelen B. , Sionov E. , Polacheck I.
Published: August 2007

We describe a case of
Pichia farinosa
bloodstream infection in a lymphoma patient. Phenotypic methods failed to identify the isolate, which was identified by sequence-based methods. This case highlights the importance of implementing molecular methods for the identification of rare fungal pathogens.
Large Sequence Polymorphisms Classify
Mycobacterium tuberculosis
Strains with Ancestral Spoligotyping Patterns
Authors: Flores Laura , Van Tran , Narayanan Sujatha , DeRiemer Kathryn , Kato-Maeda Midori , Gagneux Sebastien
Published: August 2007

Genomic deletion analysis revealed that strains of
Mycobacterium tuberculosis
exhibiting spoligotyping patterns with almost all spacers present belong either to a strain lineage that includes the W-Beijing strain family or to the ancestral strain lineage of
M. tuberculosis
.
Peritonitis Due to
Blastobotrys proliferans
in a Patient Undergoing Continuous Ambulatory Peritoneal Dialysis
Authors: Quirin N. , Desnos-Ollivier M. , Cantin J. F. , Valery J. C. , Doussy Y. , Goursaud R. , Dromer F. , Tivollier J. M.
Published: August 2007

Blastobotrys proliferans
is an ascomycetous yeast never previously reported as a human pathogen. Here we report a case of peritonitis due to
Blastobotrys proliferans
in a 46-year-old man undergoing peritoneal dialysis.
Analysis of Group B Streptococcal Isolates from Infants and Pregnant Women in Portugal Revealing Two Lineages with Enhanced Invasiveness
Authors: Martins E. R. , Pessanha M. A. , Ramirez M. , Melo-Cristino J.
Published: August 2007

The populations of group B streptococcus (GBS) associated with vaginal carriage in pregnant women and invasive neonatal infections in Portugal were compared. GBS isolates were characterized by serotyping, pulsed-field gel electrophoresis (PFGE) profiling, and multilocus sequence typing (MLST). Serotypes III and V accounted for 44% of all colonization isolates (
n
= 269), whereas serotypes III and Ia amounted to 69% of all invasive isolates (
n
= 64). Whereas serotype Ia was associated with early-onset disease (EOD), serotype III was associated with late-onset disease (LOD). Characterization by PFGE and MLST identified very diverse populations in carriage and invasive disease. Serotype Ia was represented mainly by a single PFGE cluster defined by sequence type 23 (ST23) and the infrequent ST24. In contrast, serotype III was found in a large number of PFGE clusters and STs, but a single PFGE cluster defined by ST17 was found to be associated with invasive disease. Although serotype III was associated only with LOD, ST17 showed an enhanced capacity to cause both EOD and LOD. Our data reinforce the evidence for enhanced invasiveness of ST17 and identify a lineage expressing serotype Ia capsule and represented by ST23 and ST24 as having enhanced potential to cause EOD.
Ribavirin Reveals a Lethal Threshold of Allowable Mutation Frequency for Hantaan Virus
Authors: Chung Dong-Hoon , Sun Yanjie , Parker William B. , Arterburn Jeffrey B. , Bartolucci Al , Jonsson Colleen B.
Published: August 2007

The broad spectrum of antiviral activity of ribavirin (RBV) lies in its ability to inhibit IMP dehydrogenase, which lowers cellular GTP. However, RBV can act as a potent mutagen for some RNA viruses. Previously we have shown a lack of correlation between antiviral activity and GTP repression for Hantaan virus (HTNV) and evidence for RBV's ability to promote error-prone replication. To further explore the mechanism of RBV, GTP levels, specific infectivity, and/or mutation frequency was measured in the presence of RBV, mycophenolic acid (MPA), selenazofurin, or tiazofurin. While all four drugs resulted in a decrease in the GTP levels and infectious virus, only RBV increased the mutation frequency of viral RNA (vRNA). MPA, however, could enhance RBV's mutagenic effect, which suggests distinct mechanisms of action for each. Therefore, a simple drop in GTP levels does not drive the observed error-prone replication. To further explore RBV's mechanism of action, we made a comprehensive analysis of the mutation frequency over several RBV concentrations. Of importance, we observed that the viral population reached a threshold after which mutation frequency did not correlate with a dose-dependent decrease in the level of vRNA, PFU, or [RTP]/[GTP] (where RTP is ribavirin-5′-triphosphate) over these same concentrations of RBV. Modeling of the relationship of mutation frequency and drug concentration showed an asymptotic relationship at this point. After this threshold, approximately 57% of the viral cDNA population was identical to the wild type. These studies revealed a lethal threshold, after which we did not observe a complete loss of the quasispecies structure of the wild-type genome, although we observed extinction of HTNV.
Estimating the Effectiveness of Simian Immunodeficiency Virus-Specific CD8+T Cells from the Dynamics of Viral Immune Escape
Authors: Mandl Judith N. , Regoes Roland R. , Garber David A. , Feinberg Mark B.
Published: August 2007

Antiviral CD8+T cells are thought to play a significant role in limiting the viremia of human and simian immunodeficiency virus (HIV and SIV, respectively) infections. However, it has not been possible to measure the in vivo effectiveness of cytotoxic T cells (CTLs), and hence their contribution to the death rate of CD4+T cells is unknown. Here, we estimated the ability of a prototypic antigen-specific CTL response against a well-characterized epitope to recognize and kill infected target cells by monitoring the immunodominant Mamu-A*01-restricted Tat SL8 epitope for escape from Tat-specific CTLs in SIVmac239-infected macaques. Fitting a mathematical model that incorporates the temporal kinetics of specific CTLs to the frequency of Tat SL8 escape mutants during acute SIV infection allowed us to estimate the in vivo killing rate constant per Tat SL8-specific CTL. Using this unique data set, we show that at least during acute SIV infection, certain antiviral CD8+T cells can have a significant impact on shortening the longevity of infected CD4+T cells and hence on suppressing virus replication. Unfortunately, due to viral escape from immune pressure and a dependency of the effectiveness of antiviral CD8+T-cell responses on the availability of sufficient CD4+T cells, the impressive early potency of the CTL response may wane in the transition to the chronic stage of the infection.
Plasma polychlorobiphenyl and organochlorine pesticide level and risk of major lymphoma subtypes
Authors: Cocco P , Brennan P , Ibba A , de Sanjosé Llongueras S , Maynadié M , Nieters A , Becker N , Ennas M G , Tocco M G , Boffetta P
Published: August 2007

Background:

There is conflicting epidemiological evidence concerning an increase in risk of non-Hodgkin’s lymphoma (NHL) associated with elevated blood levels of persistent organochlorine (OC) pesticides and polychlorobiphenyls (PCBs).

Methods:

We measured the concentration of 17 OC pesticides, including hexachlorobenzene (HCB), four lindane isomers (α-, β-, γ- and δ-hexachlorocyclohexane (HCH)), two chlordane species (heptachlor and oxy-chlordane), four cyclodiene insecticides (aldrin, dieldrin, endrin and mirex), six dichloro-diphenyl-trichloroethane (DDT) isomers and nine PCB congeners (PCBs 28, 52, 101, 118, 138, 153, 170, 180 and 194) in plasma samples of 377 subjects, including 174 NHL cases and 203 controls from France, Germany and Spain. The risk of NHL and its major subtypes associated with increasing blood levels of OC pesticides and PCBs was calculated using unconditional logistic regression.

Results:

Risk of NHL, diffuse large B cell lymphoma (DLBCL) and chronic lymphatic leukaemia (CLL) did not increase with plasma levels of HCB, β-HCH,p,p′-dichloro-diphenyl-dichloroethylene (DDE), or total and individual PCBs or their functional groups, in the overall study population. Substantial heterogeneity in DLBCL risk associated with immunotoxic PCBs (p = 0.03) existed between the Spanish subgroup (odds ratio (OR) for immunotoxic PCB plasma level above the median vs below the median was 0.7, 95% CI 0.3 to 1.6) and the French and German subgroups combined (OR 3.2, 95% CI 0.9 to 11.5).

Conclusion:

We did not find evidence of an association between NHL risk and plasma level of OC pesticides and PCBs.
SPATIALLY RESOLVED MAGNETIC RESPONSE IN CORE SHELL NANOPARTICLES
Authors: FAUTH K. , GOERING E. , THEIL-KUHN L.
Published: August 2007

X-ray magnetic circular dichroism is applied to investigate the magnetic response of cuboidal Fe/Fe oxide core shell nanoparticles. Characteristic differences observed in electron and fluorescence detection modes are observed. Total yield detection, overemphasizing the internal metal oxide interface, is still able to detect local magnetization changes that have too little weight in volumetric detection to be observed there.
Institutional Perspectives on Law, Work, and Family
Authors: Albiston Catherine
Published: August 2007

Work and family scholarship increasingly focuses on how institutions constrain the choices of families struggling to balance market work with care work. Recent legal reforms, including the Family and Medical Leave Act, also focus on institutional reform to alleviate work/family conflict. This article reviews important empirical questions raised by this institutional turn in both law and social science. How have changes in the institutions of family and work contributed to work/family conflict? Have legal reforms produced more egalitarian sharing of care work between men and women? How do work organizations respond to these legal mandates? How have organizational and cultural institutions hindered or given support to laws that attempt to reform the relationship between work and family? Empirical research indicates that legal reforms have brought about important changes but that entrenched work practices and cultural norms around work, family, and gender continue to generate institutional resistance to social change.
Differential effects of volatile and intravenous anesthetics on the activity of human TASK-1
Authors: Putzke C. , Hanley P. J. , Schlichthörl G. , Preisig-Müller R. , Rinné S. , Anetseder M. , Eckenhoff R. , Berkowitz C. , Vassiliou T. , Wulf H. , Eberhart L.
Published: August 2007

Volatile anesthetics have been shown to activate various two-pore (2P) domain K+ (K2P) channels such as TASK-1 and TREK-1 (TWIK-related acid-sensitive K+ channel), and mice deficient in these channels are resistant to halothane-induced anesthesia. Here, we investigated whether K2P channels were also potentially important targets of intravenous anesthetics. Whole cell patch-clamp techniques were used to determine the effects of the commonly used intravenous anesthetics etomidate and propofol on the acid-sensitive K+ current in rat ventricular myocytes (which strongly express TASK-1) and selected human K2P channels expressed in Xenopus laevis oocytes. In myocytes, etomidate decreased both inward rectifier K+ (Kir) current ( IK1) and acid-sensitive outward K+ current at positive potentials, suggesting that this drug may inhibit TASK channels. Indeed, in addition to inhibiting guinea pig Kir2.1 expressed in oocytes, etomidate inhibited human TASK-1 (and TASK-3) in a concentration-dependent fashion. Propofol had no effect on human TASK-1 (or TASK-3) expressed in oocytes. Moreover, we showed that, similar to the known effect of halothane, sevoflurane and the purified R-(−)- and S-(+)-enantiomers of isoflurane, without stereoselectivity, activated human TASK-1. We conclude that intravenous and volatile anesthetics have dissimilar effects on K2P channels. Human TASK-1 (and TASK-3) are insensitive to propofol but are inhibited by supraclinical concentrations of etomidate. In contrast, stimulatory effects of sevoflurane and enantiomeric isoflurane on human TASK-1 can be observed at clinically relevant concentrations.
Sex and sex hormones influence the development of albuminuria and renal macrophage infiltration in spontaneously hypertensive rats
Authors: Sullivan Jennifer C. , Semprun-Prieto Laura , Boesen Erika I. , Pollock David M. , Pollock Jennifer S.
Published: August 2007

There is a sex difference in hypertensive renal injury, with men experiencing greater severity and a more rapid progression of renal disease than women; however, the molecular mechanisms protecting against renal injury in women are unknown. The goal of this study was to determine whether sex hormones modulate blood pressure and the progression of albuminuria during the developmental phase of hypertension in male and female spontaneously hypertensive rats (SHR). Studies were also performed to examine how sex and sex hormones influence two major risk factors for albuminuria, overactivation of the renin-angiotensin system and oxidative stress. Blood pressure was measured by telemetry in gonad-intact and gonadectomized male and female SHR. Microalbumin excretion, measured over time, and macrophage infiltration were used to assess renal health. Male SHR had significantly higher blood pressures than female SHR, and gonadectomy decreased blood pressures in males with no effect in females. Male SHR displayed a gonad-sensitive increase in albuminuria over time, and female SHR had a gonad-sensitive suppression in macrophage infiltration. Female SHR had greater plasma ANG II levels and similar levels of renal cortical ANG II vs. levels shown in males but less AT1-receptor protein expression in the renal cortex. Female SHR also had a gonad-sensitive decrease in renal oxidative stress. Therefore, the renal protection afforded to female SHR is associated with lower blood pressure, decreased macrophage infiltration, and decreased levels of oxidative stress.
Rapid screening of glomerular slit diaphragm integrity in larval zebrafish
Authors: Hentschel Dirk M. , Mengel Michael , Boehme Lisa , Liebsch Fabian , Albertin Caroline , Bonventre Joseph V. , Haller Hermann , Schiffer Mario
Published: August 2007

Gene array-type experiments have identified large numbers of genes thought to be important for the integrity of the glomerular slit diaphragm. Confirmation of individual proteins has been limited by the expenses and time involved in generating transgenic or knockout mice for each candidate. We present a functional screening assay based on the clearance of a 70-kDa fluorescent dextran in another vertebrate system that is rapid and low in cost. In the pronephric glomerulus of larval zebrafish, we have demonstrated quantifiable loss of slit diaphragm integrity in a zebrafish model of puromycin aminonucleoside (PA) toxicity. In addition, after knockdown of CD2-associated protein (CD2AP) and podocin, two well-characterized genetic contributors to podocyte differentiation in mammals, we observed glomerular loss of serum macromolecules similar to that seen in mammalian kidneys with inborn mutations in these genes. Increased filtration of 70-kDa FITC-labeled dextran correlates with effacement of podocyte foot processes in ultrastructural analysis. These findings document the value of the zebrafish model in genomics and pharmacological screening applications.
Expression of CCN1 (CYR61) in developing, normal, and diseased human kidney
Authors: Sawai Kazutomo , Mukoyama Masashi , Mori Kiyoshi , Kasahara Masato , Koshikawa Masao , Yokoi Hideki , Yoshioka Tetsuro , Ogawa Yoshihisa , Sugawara Akira , Nishiyama Hiroyuki , Yamada Shigehito , Kuwahara Takashi , Saleem Moin A. , Shiota Kohei , Ogawa Osamu , Miyazato Mikiya , Kangawa Kenji , Nakao Kazuwa
Published: August 2007

CCN1 (cysteine-rich protein 61; Cyr61) is an extracellular matrix-associated signaling molecule that functions in cell migration, adhesion, and differentiation. We previously reported that CCN1 is induced at podocytes in rat anti-Thy-1 glomerulonephritis, a well-known model of reversible glomerular injury, but its expression and significance in the human kidney remain totally unknown (Sawai K, Mori K, Mukoyama M, Sugawara A, Suganami T, Koshikawa M, Yahata K, Makino H, Nagae T, Fujinaga Y, Yokoi H, Yoshioka T, Yoshimoto A, Tanaka I, Nakao K. J Am Soc Nephrol 14: 1154–1163, 2003). Here we report that, in the human kidney, CCN1 expression was confined to podocytes in normal adult and embryonic glomeruli from the capillary loop stage. Podocyte CCN1 expression was decreased in IgA nephropathy, diabetic nephropathy, and membranous nephropathy, whereas it remained unchanged in minimal change disease and focal segmental glomerulosclerosis. Downregulation of CCN1 was significantly greater in diseased kidneys with severe mesangial expansion. CCN1 protein was also localized in the thick ascending limb of Henle's loop, distal and proximal tubules, and collecting ducts, which was not altered in diseased kidneys. In vitro, recombinant CCN1 protein enhanced endothelial cell adhesion, whereas it prominently inhibited mesangial cell adhesion. CCN1 also completely suppressed mesangial cell migration, suggesting its role as a mesangial-repellent factor. In cultured podocytes, CCN1 markedly induced the expression of cyclin-dependent kinase inhibitor p27Kip1 as well as synaptopodin in a dose-dependent manner and suppressed podocyte migration. These data indicate that CCN1 is expressed in podocytes, can act on glomerular cells to modulate glomerular remodeling, and is downregulated in diseased kidneys, suggesting that impairment of CCN1 expression in podocytes may contribute to the progression of glomerular disease with mesangial expansion.
Gentamicin suppresses endotoxin-driven TNF-α production in human and mouse proximal tubule cells
Authors: Zager Richard A. , Johnson Ali C. M. , Geballe Adam
Published: August 2007

Gentamicin is a mainstay in treating gram-negative sepsis. However, it also may potentiate endotoxin (LPS)-driven plasma TNF-α increases. Because gentamicin accumulates in renal tubules, this study addressed whether gentamicin directly alters LPS-driven tubular cell TNF-α production. HK-2 proximal tubular cells were incubated for 18 h with gentamicin (10–2,000 μg/ml). Subsequent LPS-mediated TNF-α increases (at 3 or 24 h; protein/mRNA) were determined. Gentamicin effects on overall protein synthesis ([35S]methionine incorporation), monocyte chemoattractant protein-1 (MCP-1) levels, and LPS-stimulated TNF-α generation by isolated mouse proximal tubules also were assessed. Finally, because gentamicin undergoes partial biliary excretion, its potential influence on gut TNF-α/MCP-1 mRNAs was probed. Gentamicin caused striking, dose-dependent inhibition of LPS-driven TNF-α production (up to 80% in HK-2 cells/isolated tubules). Surprisingly, this occurred despite increased TNF-α mRNA accumulation. Comparable changes in MCP-1 were observed. These changes were observed at clinically relevant gentamicin concentrations and despite essentially normal overall protein synthetic rates. Streptomycin also suppressed LPS-driven TNF-α increases, suggesting an aminoglycoside drug class effect. Gentamicin doubled basal TNF-α mRNA in cecum and in small intestine after LPS. Gentamicin can suppress LPS-driven TNF-α production in proximal tubule cells, likely by inhibiting its translation. Overall preservation of protein synthesis and comparable MCP-1 suppression suggest a semiselective blockade within the LPS inflammatory mediator cascade. These results, coupled with increases in gut TNF-α/MCP-1 mRNAs, imply that gentamicin may exert protean, countervailing actions on systemic cytokine/chemokine production during gram-negative sepsis.
Spectral Composition of Concurrent Noise Affects Neuronal Sensitivity to Interaural Time Differences of Tones in the Dorsal Nucleus of the Lateral Lemniscus
Authors: Siveke Ida , Leibold Christian , Grothe Benedikt
Published: August 2007

We are regularly exposed to several concurrent sounds, producing a mixture of binaural cues. The neuronal mechanisms underlying the localization of concurrent sounds are not well understood. The major binaural cues for localizing low-frequency sounds in the horizontal plane are interaural time differences (ITDs). Auditory brain stem neurons encode ITDs by firing maximally in response to “favorable” ITDs and weakly or not at all in response to “unfavorable” ITDs. We recorded from ITD-sensitive neurons in the dorsal nucleus of the lateral lemniscus (DNLL) while presenting pure tones at different ITDs embedded in noise. We found that increasing levels of concurrent white noise suppressed the maximal response rate to tones with favorable ITDs and slightly enhanced the response rate to tones with unfavorable ITDs. Nevertheless, most of the neurons maintained ITD sensitivity to tones even for noise intensities equal to that of the tone. Using concurrent noise with a spectral composition in which the neuron's excitatory frequencies are omitted reduced the maximal response similar to that obtained with concurrent white noise. This finding indicates that the decrease of the maximal rate is mediated by suppressive cross-frequency interactions, which we also observed during monaural stimulation with additional white noise. In contrast, the enhancement of the firing rate to tones at unfavorable ITD might be due to early binaural interactions (e.g., at the level of the superior olive). A simple simulation corroborates this interpretation. Taken together, these findings suggest that the spectral composition of a concurrent sound strongly influences the spatial processing of ITD-sensitive DNLL neurons.
Management of Non-Pain Symptoms in Pediatric Palliative Care
Authors: Friedrichsdorf Stefan J. , Collins John J.
Published: August 2007

The majority of children dying from a life-limiting condition suffer from distressing symptoms during their last weeks of life. The provision of current state-of-the-art symptom control is paramount for any health care professional working with dying children, but treatment guidelines are sparse. This article reviews the management of integrative and pharmacological therapies for acute seizure control, anorexia, death rattle, dyspnea, nausea and vomiting, and muscle spasm during the end-of-life period of children and teens. Several myths and misconceptions have led to inadequate symptom control in children with a terminal disease. A dying child is often highly symptomatic, and providing professional integrative and pharmacological symptom relief is one of the many precincts of pediatric palliative care.
Cardiac Energy Metabolism in Obesity
Authors: Lopaschuk Gary D. , Folmes Clifford D.L. , Stanley William C.
Published: August 2007

Obesity results in marked alterations in cardiac energy metabolism, with a prominent effect being an increase in fatty acid uptake and oxidation by the heart. Obesity also results in dramatic changes in the release of adipokines, such as leptin and adiponectin, both of which have emerged as important regulators of cardiac energy metabolism. The link among obesity, cardiovascular disease, lipid metabolism, and adipokine signaling is complex and not well understood. However, optimizing cardiac energy metabolism in obese subjects may be one approach to preventing and treating cardiac dysfunction that can develop in this population. This review discusses what is presently known about the effects of obesity and the impact adipokines have on cardiac energy metabolism and insulin signaling. The clinical implications of obesity and energy metabolism on cardiac disease are also discussed.
6-Hour to 1-Year Variance of Five Global Precipitation Sets
Authors: Ruane Alex C. , Roads John O.
Published: August 2007

Three-hourly time series of precipitation from three high-resolution precipitation products [Tropical Rainfall Measuring Mission (TRMM) algorithm 3B-42, the Climate Prediction Center’s morphing method (CMORPH), and the Precipitation Estimation from Remotely Sensed Information Using Artificial Neural Networks (PERSIANN)] and two reanalyses are examined for their frequency characteristics using broad and narrow variance categories. After isolating the diurnally forced peaks (at 24, 12, 8, and 6 h), the power spectra are divided into comprehensive broad bands comprising the annual (∼80 days–1 yr), intraseasonal (20 to ∼80 days), slow (6–20 days) and fast (36 h–6 days) synoptic, and high-frequency (6–36 h) periods. Global maps accounting for 100% of precipitation’s variance are analyzed to identify unique regional behaviors.

Annual variability is strongest over regions affected by the seasonal migration of the intertropical convergence zone, as well as over monsoonal regions. The intraseasonal band displays off-equatorial evidence of the Madden–Julian oscillation (MJO), particularly in the Indian Ocean, but the MJO’s rainfall is partially manifested in the slow synoptic band and at higher frequencies. The fast synoptic band is particularly strong over the oceans, while high-frequency variability is enhanced over land by more extreme surface gradients. Diurnal variance is strongest at low latitudes and is pronounced over regions with well-known diurnal circulations, including mountains and coastlines. Interproduct and intermodel differences also indicate biases of the precipitation product algorithms and convective parameterizations, including a strong bias toward low-frequency variability in the relaxed Arakawa–Schubert parameterization employed by one of the reanalyses, as well as increased white-spectral characteristics over land in the precipitation products.
Mechanisms Controlling the Interannual Variation of Mixed Layer Temperature Averaged over the Niño-3 Region
Authors: Kim Seung-Bum , Lee Tong , Fukumori Ichiro
Published: August 2007

Processes controlling the interannual variation of mixed layer temperature (MLT) averaged over the Niño-3 domain (5°N–5°S, 150°–90°W) are studied using an ocean data assimilation product that covers the period of 1993–2003. The overall balance is such that surface heat flux opposes the MLT change but horizontal advection and subsurface processes assist the change. Advective tendencies are estimated here as the temperature fluxes through the domain’s boundaries, with the boundary temperature referenced to the domain-averaged temperature to remove the dependence on temperature scale. This allows the authors to characterize external advective processes that warm or cool the water within the domain as a whole. The zonal advective tendency is caused primarily by large-scale advection of warm-pool water through the western boundary of the domain. The meridional advective tendency is contributed to mostly by Ekman current advecting large-scale temperature anomalies through the southern boundary of the domain. Unlike many previous studies, the subsurface processes that consist of vertical mixing and entrainment are explicitly evaluated. In particular, a rigorous method to estimate entrainment allows an exact budget closure. The vertical mixing across the mixed layer (ML) base has a contribution in phase with the MLT change. The entrainment tendency due to the temporal change in ML depth is negligible compared to other subsurface processes. The entrainment tendency by vertical advection across the ML base is dominated by large-scale changes in upwelling and the temperature of upwelling water. Tropical instability waves (TIWs) result in smaller-scale vertical advection that warms the domain during La Niña cooling events. However, such a warming tendency is overwhelmed by the cooling tendency associated with the large-scale upwelling by a factor of 2. In summary, all the balance terms are important in the MLT budget except the entrainment due to lateral induction and temporal variation in ML depth. All three advective tendencies are primarily caused by large-scale and low-frequency processes, and they assist the Niño-3 MLT change.

When the advective tendencies are evaluated by spatially averaging the conventional local advection of temperature, the apparent effects of currents with spatial scales smaller than the domain (such as TIWs) become very important as they redistribute heat within the Niño-3 domain. As a result, for example, the averaged zonal advective tendency counteracts rather than assists the Niño-3 MLT change. However, such internal redistribution of heat does not represent external processes that control the domain-averaged MLT.
Investigation of the Summer Climate of the Contiguous United States and Mexico Using the Regional Atmospheric Modeling System (RAMS). Part II: Model Climate Variability
Authors: Castro Christopher L. , Pielke Roger A. , Adegoke Jimmy O. , Schubert Siegfried D. , Pegion Phillip J.
Published: August 2007

Summer simulations over the contiguous United States and Mexico with the Regional Atmospheric Modeling System (RAMS) dynamically downscaling the NCEP–NCAR Reanalysis I for the period 1950–2002 (described in Part I of the study) are evaluated with respect to the three dominant modes of global SST. Two of these modes are associated with the statistically significant, naturally occurring interannual and interdecadal variability in the Pacific. The remaining mode corresponds to the recent warming of tropical sea surface temperatures. Time-evolving teleconnections associated with Pacific SSTs delay or accelerate the evolution of the North American monsoon. At the period of maximum teleconnectivity in late June and early July, there is an opposite relationship between precipitation in the core monsoon region and the central United States. Use of a regional climate model (RCM) is essential to capture this variability because of its representation of the diurnal cycle of convective rainfall. The RCM also captures the observed long-term changes in Mexican summer rainfall and suggests that these changes are due in part to the recent increase in eastern Pacific SST off the Mexican coast. To establish the physical linkage to remote SST forcing, additional RAMS seasonal weather prediction mode simulations were performed and these results are briefly discussed. In order for RCMs to be successful in a seasonal weather prediction mode for the summer season, it is required that the GCM provide a reasonable representation of the teleconnections and have a climatology that is comparable to a global atmospheric reanalysis.
Changes in Cloud-Ceiling Heights and Frequencies over the United States since the Early 1950s
Authors: Sun Bomin , Karl Thomas R. , Seidel Dian J.
Published: August 2007

U.S. weather stations operated by NOAA’s National Weather Service (NWS) have undergone significant changes in reporting and measuring cloud ceilings. Stations operated by the Department of Defense have maintained more consistent reporting practices. By comparing cloud-ceiling data from 223 NWS first-order stations with those from 117 military stations, and by further comparison with changes in physically related parameters, inhomogeneous records, including all NWS records based only on automated observing systems and the military records prior to the early 1960s, were identified and discarded. Data from the two networks were then used to determine changes in daytime ceiling height (the above-ground height of the lowest sky-cover layer that is more than half opaque) and ceiling occurrence frequency (percentage of total observations that have ceilings) over the contiguous United States since the 1950s.

Cloud-ceiling height in the surface–3.6-km layer generally increased during 1951–2003, with more significant changes in the period after the early 1970s and in the surface–2-km layer. These increases were mostly over the western United States and in the coastal regions. No significant change was found in surface–3.6-km ceiling occurrence during 1951–2003, but during the period since the early 1970s, there is a tendency for a decrease in frequency of ceilings with height below 3.6 km. Cloud-ceiling heights above 3.6 km have shown no significant changes in the past 30 yr, but there has been an increase in frequency, consistent with the increase in ceiling height below 3.6 km. For the surface–3.6-km layer, physically consistent changes were identified as related to changes in ceiling height and frequency of occurrence. This included reductions in precipitation frequency related to low ceiling frequency, and surface warming and decreasing relative humidity accompanying increasing ceiling heights during the past 30 yr.
Midlatitude Wind Stress–Sea Surface Temperature Coupling in the Vicinity of Oceanic Fronts
Authors: Spall Michael A.
Published: August 2007

The influences of strong gradients in sea surface temperature on near-surface cross-front winds are explored in a series of idealized numerical modeling experiments. The atmospheric model is the Naval Research Laboratory Coupled Ocean–Atmosphere Mesoscale Prediction System (COAMPS) model, which is fully coupled to the Regional Ocean Modeling System (ROMS) ocean model. A series of idealized, two-dimensional model calculations is carried out in which the wind blows from the warm-to-cold side or the cold-to-warm side of an initially prescribed ocean front. The evolution of the near-surface winds, boundary layer, and thermal structure is described, and the balances in the momentum equation are diagnosed. The changes in surface winds across the front are consistent with previous models and observations, showing a strong positive correlation with the sea surface temperature and boundary layer thickness. The coupling arises mainly as a result of changes in the flux Richardson number across the front, and the strength of the coupling coefficient grows quadratically with the strength of the cross-front geostrophic wind. The acceleration of the winds over warm water results primarily from the rapid change in turbulent mixing and the resulting unbalanced Coriolis force in the vicinity of the front. Much of the loss/gain of momentum perpendicular to the front in the upper and lower boundary layer results from acceleration/deceleration of the flow parallel to the front via the Coriolis term. This mechanism is different from the previously suggested processes of downward mixing of momentum and adjustment to the horizontal pressure gradient, and is active for flows off the equator with sufficiently strong winds. Although the main focus of this work is on the midlatitude, strong wind regime, calculations at low latitudes and with weak winds show that the pressure gradient and turbulent mixing terms dominate the cross-front momentum budget, consistent with previous work.
Accuracy of Atlantic and Eastern North Pacific Tropical Cyclone Intensity Forecast Guidance
Authors: Elsberry Russell L. , Lambert Tara D. B. , Boothe Mark A.
Published: August 2007

Five statistical and dynamical tropical cyclone intensity guidance techniques available at the National Hurricane Center (NHC) during the 2003 and 2004 Atlantic and eastern North Pacific seasons were evaluated within three intensity phases: (I) formation; (II) early intensification, with a subcategory (IIa) of a decay and reintensification cycle; and (III) decay. In phase I in the Atlantic, the various techniques tended to predict that a tropical storm would form from six tropical depressions that did not develop further, and thus the tendency was for false alarms in these cases. For the other 24 depressions that did become tropical storms, the statistical–dynamical techniques, statistical hurricane prediction scheme (SHIPS) and decay SHIPS (DSHIPS), have some skill relative to the 5-day statistical hurricane intensity forecast climatology and persistence technique, but they also tend to intensify all depressions and thus are prone to false alarms. In phase II, the statistical–dynamical models SHIPS and DSHIPS do not predict the rapid intensification cases (≥30 kt in 24 h) 48 h in advance. Although the dynamical Geophysical Fluid Dynamics Interpolated model does predict rapid intensification, many of these cases are at the incorrect times with many false alarms. The best performances in forecasting at least 24 h in advance the 21 decay and reintensification cycles in the Atlantic were the three forecasts by the dynamical Geophysical Fluid Dynamics Model-Navy (interpolated) model. Whereas DSHIPS was the best technique in the Atlantic during the decay phase III, none of the techniques excelled in the eastern North Pacific. All techniques tend to decay the tropical cyclones in both basins too slowly, except that DSHIPS performed well (12 of 18) during rapid decay events in the Atlantic. This evaluation indicates where NHC forecasters have deficient guidance and thus where research is necessary for improving intensity forecasts.
MesoLAPS Predictions of Low-Level Convergence Lines over Northeastern Australia
Authors: Weinzierl Bernadett , Smith Roger K. , Reeder Michael J. , Jackson Gordon E.
Published: August 2007

The prediction of low-level convergence lines over northeastern Australia such as those which give rise to the “morning glory” phenomenon and the north Australian cloud line (NACL) are investigated using MesoLAPS, a mesoscale version of the Australian Bureau of Meteorology’s operational Limited Area Prediction System. The model is used also to examine aspects of the dynamics of such lines. The predictions were made during the Gulf Lines Experiment in 2002 and are compared here with data collected during the experiment. The ability of MesoLAPS to forecast the convergence lines is investigated in detail for selected cases. In two cases with well-developed southerly morning glory disturbances, the model was able to capture the separation of a borelike disturbance from an airmass change, although the model does not have the resolution to capture the wavelike structures that develop at the leading edge of the bore waves. An analysis of the entire 44-day period between 11 September and 24 October shows that MesoLAPS has significant skill in forecasting the lines, but it does not capture all of them. About 85% of forecasts of northeasterly morning glories and southerly morning glories, or of their nonoccurrence, were correct, while the corresponding percentage for the NACL was about 65%. However, about 15% of northeasterly morning glories and about 35% of NACL events that occurred were not forecast by the model. Also, only 6 out of 11 southerly morning glories were forecast. A detailed analysis of the MesoLAPS calculations indicates that the broad-scale generation mechanisms of northeasterly and southerly morning glories are similar and it enables the construction of a conceptual model for the generation of southerly morning glories.