bluuebunny/crossref_metadata_2025 huggingface dataset:
Mycobacterium tuberculosis at autopsy—exposure and protection: an old adversary revisited
Authors: Flavin R J , Gibbons N , O’Briain D S
Published: May 2006

Background:The risk of encountering tuberculosis (TB) has reduced with the decreased incidence of the disease; however, it still can be found at autopsy.

Aim:To assess the magnitude of exposure toMycobacterium tuberculosisat autopsy in a large general hospital setting, in a country with low incidence.

Methods:Retrospective search of the autopsy records from 1991 to 2004. Patients’ records and histological slides were reviewed, and medical personnel interviewed.

Results:15 cases of active TB were identified in the 14-year period, during which 4930 autopsies were performed (1 case per 329 autopsies); of these, 10 cases were unsuspected (67%). Five of these cases contained abundant acid-fast bacilli. Patients tended to be middle aged and males with complex clinical histories; two were HIV positive. Two patients were brought in dead to hospital, with no clinical indication of TB. Of 15 autopsy staff, 1 required chemoprophylaxis but none contracted TB.

Conclusion:The risk of unexpectedly encountering TB at autopsy continues even in a low-risk European setting. It has implications for the health of autopsy room staff, autopsy room design and ventilation, choice of protective equipment and for the public health service. Protective strategies include assessment of the risk of a case being infected, early recognition of gross lesions, use of methods for reducing the production of infected aerosols and protection against any aerosols created.
Clinical significance of plasmacytosis in the day+14 bone marrow of patients with acute myeloid leukaemia undergoing induction chemotherapy
Authors: Al-Shughair Nada , Al-Dawsari Ghuzayel , Gyger Martin , Mohamed Gamal , Roberts George
Published: May 2006

Background:The design of chemotherapy-induction regimens for acute myeloid leukaemia (AML) is directed towards the early elimination of bone marrow (BM) leukaemic blast cells (LBCs). Patients with AML after induction show LBC reduction in a hypoplastic BM and also demonstrate a varying number of residual BM plasma cells (PCs).

Aim:To relate PC number to several blood and BM parameters as well as clinical features such as infection and survival.

Methods:On the 14th day after the start of chemotherapy (D+14) BM samples were examined for residual PCs in 60 adult (⩾15 years) patients undergoing AML-induction chemotherapy, and the proportion of PCs was related to blood and BM parameters including French–American–British (FAB) subtype, other inflammatory cells, antecedent infection, attainment of complete remission and 36-month survival.

Results:Median PC proportion of 11.3% (range 0.1–48.7%) in D+14 BM aspirates and 10.7% (0.6–41%) in trephine biopsies was observed. Their number showed a direct relationship with residual BM lymphocytes (r = 0.368; p = 0.025). Higher numbers of residual PCs also reflected the presence of infection before diagnosis and coincident with treatment (p = 0.039). Although we could not demonstrate an association between PC numbers and 36-month survival, PC numbers were significantly higher in patients with residual leukaemia at D>14 (p = 0.007).

Conclusion:D+14 BM PC number reflects the effectiveness of induction chemotherapy and the presence of antecedent inflammation or infection.
High stromal versican expression predicts unfavourable outcome in oral squamous cell carcinoma
Authors: Pukkila Matti , Kosunen Ari , Ropponen Kirsi , Virtaniemi Jukka , Kellokoski Jari , Kumpulainen Eero , Pirinen Risto , Nuutinen Juhani , Johansson Risto , Kosma Veli-Matti
Published: May 2006

Background:Versican, an extracellular matrix proteoglycan, has been noted to be expressed in several malignant tumours and has been suggested to play an important role in cancer development and tumour growth.

Aims:To investigate whether the versican expression level in the peritumoural stromal tissue of primary oral squamous cell carcinoma (OSCC) predicts relapse-free or disease-specific survival. Also, to study the associations between versican expression and several other clinicopathological variables, as well as tumour cell proliferation.

Methods:Immunohistochemistry was used to study the expression of versican and tumour cell proliferative activity in 139 OSCCs. All pertinent clinical data were collected retrospectively from the hospital records.

Results:In this cohort, versican expression did not correlate with the clinicopathological factors or tumour cell proliferation. In univariate analyses, higher risk for disease recurrence was associated with higher stromal versican expression score (p = 0.02), positive neck node status (p = 0.02), lower Karnofsky performance status (p = 0.03) and higher tumour cell proliferation index (p = 0.04). Increased disease-specific risk of death was associated with high stromal versican expression score (p = 0.005) higher T class (p = 0.002), positive neck node status (p<0.001), higher stage (p<0.001), poorer histological differentiation (p = 0.005), worse general condition of the patient (p = 0.049) and increased tumour cell proliferative index (p = 0.02). In multivariate disease-specific survival analysis, high stromal versican expression score (p = 0.048), poorer histological differentiation (p = 0.047) and higher stage (p = 0.002) independently predicted poorer disease outcome.

Conclusions:In this cohort, increased stromal versican expression correlated with both increased risk for disease recurrence and shortened survival. High stromal versican expression may thus be considered an independent and adverse prognostic marker in OSCC.
Why I became a surgical pathologist with interest in breast disease
Authors: Page David L
Published: May 2006

Factors that influenced my decision to become a surgical pathologist are presented below. Early childhood experience shaped my interest in epidemiology and public health. Formal education at Johns Hopkins Medical School cemented my decision to become a surgical pathologist and elective time with pioneers in the field of surgical pathology sealed my career choice. As a mentor, I have tried to teach residents and fellows how to practice pathology, not merely how to make a diagnosis.
Expression of β-catenin in gastroenteropancreatic endocrine tumours: a study of 229 cases
Authors: Hervieu V , Lepinasse F , Gouysse G , Guillaud O , Barel C , Chambonniere M-L , Bringuier P-P , Poncet G , Lombard-Bohas C , Partensky C , Chayvialle J-A , Scoazec J-Y
Published: May 2006

Aims:To clarify the role of β-catenin in digestive endocrine carcinogenesis, a large and representative series of gastroenteropancreatic endocrine tumours was analysed in order to determine the incidence and pattern of β-catenin changes and to analyse the clinical and histological characteristics of the tumours presenting immunohistochemically detectable changes in β-catenin expression.

Methods:229 cases of gastroenteropancreatic endocrine tumours (stomach, 11; duodenum and ampulla, 29; jejunum and ileum, 51; appendix, 13; colon and rectum, 17; and pancreas, 108) were studied by immunohistochemistry to assess the pattern of distribution of β-catenin (membranous, cytoplasmic or nuclear). DNA was analysed to detect mutations in exon 3 of theCTNNB1gene.

Results:The distribution of immunoreactive β-catenin protein was membranous in 164 cases, cytoplasmic in 58 cases and nuclear in seven cases. No mutation was detected in exon 3 of theCTNNB1gene in any case. The seven cases with nuclear accumulation of β-catenin were large tumours (mean size 44 (standard deviation (SD) 18.5) mm) with metastases, including liver metastases in five cases, high Ki-67 index (mean 34% (SD 16.5%)) and cyclin D1 overexpression; p53 accumulation was detected in six cases. Five patients died of disease; the mean (SD) survival was 13.6 (4.8) months.

Conclusions:Immunohistochemically detectable nuclear accumulation of β-catenin is infrequent in gastroenteropancreatic endocrine tumours and is usually not associated with mutations inCNNTB1exon 3. Changes in β-catenin expression are late events in digestive endocrine carcinogenesis, associated with tumour progression and dissemination.
Reduced levels of oestrogen receptor β mRNA in Swedish patients with chronic fatigue syndrome
Authors: Gräns Hanna , Nilsson Maria , Dahlman-Wright Karin , Evengård Birgitta
Published: May 2006

Background:Chronic fatigue syndrome (CFS) is an illness with unknown aetiology and pathophysiology. The difference in incidence by sex observed for CFS indicates a role for oestrogen and oestrogen receptors in disease development. Furthermore, an immunomediated pathogenesis has been suggested for CFS, providing an additional connection to oestrogen, which displays immunomodular functions.

Aims:To investigate a possible association of oestrogen receptor (ER) mRNAs and two ERβ single-nucleotide polymorphisms (SNPs) with CFS.

Methods:Messenger RNA levels of ERα, ERβ wt and ERβ cx were investigated in peripheral blood mononuclear cells from 30 patients with CFS and 36 healthy controls by quantitative real-time polymerase chain reaction. Two ERβ SNPs were scored in the same material.

Results:The CFS group showed significantly lower mRNA expression levels of ERβ wt compared with the healthy control group. No differences were observed for ERα or ERβ cx between patients and controls. There were no significant differences in frequency for the investigated ERβ SNPs between cases and controls.

Conclusions:The reduced ERβ wt expression level observed in this study is consistent with an immune-mediated pathogenesis of CFS. Additionally, the observation that ERβ wt expression is decreased in CFS could provide an entry point to identify interesting, potentially disease-causing, candidate molecules for further study. A possible connection between oestrogen, oestrogen receptors and CFS should be evaluated further.
The reliability of assessment of oestrogen receptor expression on needle core biopsy specimens of invasive carcinomas of the breast
Authors: Hodi Zsolt , Chakrabarti Jayeta , Lee Andrew H S , Ronan John E , Elston Christopher W , Leung Cheung Kwok , Robertson John F R , Ellis Ian O
Published: May 2006

Aim:To assess the reliability of assessment of oestrogen receptor expression on needle core biopsy specimens of invasive carcinomas of the breast. Previous studies have mostly been small, with a range of agreement from 62% to 100%.

Methods:Retrospective audit of 338 tumours surgically excised within 60 days of core biopsy, that had had oestrogen receptor assessed on both the core biopsy and tumour specimens. Surgical specimens were incised when fresh to ensure good fixation. External controls including a weakly positive tumour were included in each immunohistochemistry run.

Results:Oestrogen receptor expression was bimodal, with H score in both specimens of either 0 or >50 in 96% of tumours. Using H score cut-off of 10 for positivity, there was an agreement between core and excision in 334 of 338 tumours (98.8%). All discrepancies were between weakly positive and negative tumours. Intratumoral heterogeneity could explain the one tumour that was negative on core and positive on excision. H score tended to be slightly higher on core than excision (means 146 and 136). Better fixation on the core is the most likely explanation for this and for the three tumours that were positive on core and negative on excision. Repeat staining on tumours with discrepant results gave similar results in all except one case. An internal control was present in 97% of excisions and 55% of cores of oestrogen receptor-negative tumours; the internal control stained positively in all except two sections.

Conclusion:Oestrogen receptor can be assessed reliably on needle core biopsies of invasive carcinomas of the breast.
Radial scar lesions of the breast diagnosed by needle core biopsy: analysis of cases containing occult malignancy
Authors: Douglas-Jones Anthony G , Denson Jemimah L , Cox Adam C , Harries Iwan B , Stevens Guy
Published: May 2006

Aim:To identify and review cases of false negative needle core biopsy (NCB) in the preoperative investigation of radial scar/complex sclerosing lesion (RS/CSL) lesions—that is, benign NCB from RS/CSL which contained malignancy on excision.

Methods and results:A total of 11 false negative NCB in RS/CSL lesions from 281 (3.9%) were identified (6 cases: B1, 2 cases: B2 and 3 cases: B3). In 6 of 11 cases a radial scar or stromal sclerosis was seen in NCB. Localisation biopsy showed duct carcinoma in situ in six cases, duct carcinoma in situ with invasive carcinoma in three and invasive carcinoma in two. In all 11 cases, needle tracks were identified as missing the malignant epithelium by a mean of 5 mm (median:4 mm; range:1–20 mm). In 9 of 11 cases, the malignancy was missed by <6 mm.

Conclusions:Despite evidence of accurate targeting of lesions, the use of NCB instead of fine needle aspiration cytology has not eliminated the problem of false negative biopsy in RS/CSL, and excision is recommended.
Transformed dermatofibrosarcoma protuberans: real time polymerase chain reaction detection of COL1A1–PDGFB fusion transcripts in sarcomatous areas
Authors: Szollosi Zoltan , Scholtz Beata , Egervari Kristof , Nemes Zoltan
Published: May 2006

Background:Recent cytogenetic studies have shown that reciprocal translocation t (17;22)(q22;q13) and a supernumerary ring chromosome derived from the translocation r(17;22) are highly characteristic of dermatofibrosarcoma protuberans (DFSP). The chromosomal rearrangements fuse the collagen type Iα1 (COL1A1) and the platelet-derived growth factor B-chain (PDGFB) genes. The COL1A1–PDGFB fusion transcript has been shown not only in conventional DFSP but also in a small series of DFSP with fibrosarcomatons areas (DFSP-FS) using reverse transcriptase-based conventional polymerase chain reaction. Nothing is known about the status of the COL1A1–PDGFB chimaeric gene in the pleomorphic areas of DFSP-PleoSarc (formerly known as DFSP-malignant fibrous sarcoma).

Aims:To show the COL1A1–PDGFB fusion transcript in transformed malignant fibrous histiocytoma.

Method:A real-time polymerase chain reaction assay for the COL1A1–PDGFB fusion transcript in a series of DFSP containing sarcoma was conducted to determine whether the chimaeric gene could be identified in both components of DFSP-FS and DFSP-PleoSarc. Eight cases were analysed.

Results:In seven cases, transcriptable RNA was detected, and in these cases, translocations were found between COL1A1 and PDGFB genes involving exons 27, 32, 34, 40 and 47 of the COL1A1 gene and exon 2 of the PDGFB gene.

Conclusions:From a diagnostic aspect, this assay can be particularly useful in confirming the diagnosis of sarcomatous DFSP. On the other hand, the COL1A1–PDGFB fusion gene was shown in three cases of DFSP containing pleomorphic sarcoma, which supports the theory of the common histogenesis.
UNIFIED EXPRESSIONS OF ALL INTEGRAL VARIATIONAL PRINCIPLES
Authors: HUANG YONG-CHANG , LEE XI-GUO , SHAO MING-XUE
Published: May 2006

In terms of the quantitative causal principle, this paper obtains a general variational principle, gives unified expressions of the general, Hamilton, Voss, Hölder, Maupertuis–Lagrange variational principles of integral style, the invariant quantities of the general, Voss, Hölder, Maupertuis–Lagrange variational principles are given, finally the Noether conservation charges of the general, Voss, Hölder, Maupertuis–Lagrange variational principles are deduced, and the intrinsic relations among the invariant quantities and the Noether conservation charges of all the integral variational principles are achieved.
SOME COMMENTS ON THE DIVERGENCE OF PERTURBATION SERIES IN QUANTUM ELECTRODYNAMICS
Authors: AZAM MOFAZZAL
Published: May 2006

It has been argued by Dyson that the perturbation theory in coupling constant in QED cannot be convergent. We find that similar albeit slightly different arguments lead to the divergence of the series of 1/N f expansion in QED.
DARK ENERGY: RECENT DEVELOPMENTS
Authors: STRAUMANN N.
Published: May 2006

A six-parameter cosmological model, involving a vacuum energy density that is extremely tiny compared to fundamental particle physics scales, describes a large body of increasingly accurate astronomical data. In the first part of this brief review we summarize the current situation, emphasizing recent progress. An almost infinitesimal vacuum energy is only the simplest candidate for a cosmologically significant nearly homogeneous exotic energy density with negative pressure, generically called Dark Energy. If general relativity is assumed to be also valid on cosmological scales, the existence of such a dark energy component that dominates the recent universe is now almost inevitable. We shall discuss in the second part the alternative possibility that general relativity has to be modified on distances comparable to the Hubble scale. It will turn out that observational data are further restricting theoretical speculations. Moreover, some of the recent proposals have serious defects on a fundamental level (ghosts, acausalities, superluminal fluctuations).
GRAVITOMAGNETISM AND THE SPEED OF GRAVITY
Authors: KOPEIKIN SERGEI M.
Published: May 2006

Experimental discovery of the gravitomagnetic fields generated by translational and/or rotational currents of matter is one of primary goals of modern gravitational physics. The rotational (intrinsic) gravitomagnetic field of the Earth is currently measured by the Gravity Probe B. The present paper makes use of a parametrized post-Newtonian (PN) expansion of the Einstein equations to demonstrate how the extrinsic gravitomagnetic field generated by the translational current of matter can be measured by observing the relativistic time delay caused by a moving gravitational lens. We prove that measuring the extrinsic gravitomagnetic field is equivalent to testing the relativistic effect of the aberration of gravity caused by the Lorentz transformation of the gravitational field. We show that the recent Jovian deflection experiment is a null-type experiment testing the Lorentz invariance of the gravitational field (aberration of gravity), thus, confirming existence of the extrinsic gravitomagnetic field associated with the orbital motion of Jupiter with accuracy 20%. We comment on physically inadequate interpretations of the Jovian deflection experiment given by a number of researchers who are not experts in modern VLBI techniques and the subtleties of JPL ephemeris. We propose to measure the aberration of gravity effect more accurately by observing the gravitational deflection of light by the Sun and processing VLBI observations in the geocentric frame with respect to which the Sun is moving with velocity ~30 km/s.
KINEMATIC PROPERTIES OF DAMPED LYMAN ALPHA SYSTEMS
Authors: DAS SNIGDHA , KHARE PUSHPA
Published: May 2006

In a previous paper, we determined the statistical distributions for various classes of QSO absorption systems in the framework of the CDM model of the universe with a mass distribution of dark matter halos as given by the Press Schechter mechanism. These were shown to be consistent with the observed distributions for reasonable choices of model parameters. In this paper, we generate Voigt profiles of C IV lines associated with Damped Lyman Alpha systems in the framework of this model, taking into account rotation of disks and random motion of clouds embedded in galactic halos. We compare these with the profiles for a sample of 32 Damped Lyman Alpha systems collected from the literature by performing several statistical tests. These tests compare the width and the degree of asymmetry in the line profiles produced by the rotation of randomly inclined disks and the random velocity of clouds in the galactic halos, with the corresponding quantities in the observed profiles. We find that the kinematic properties predicted by the model are in good agreement with observations provided the disk thickness is about ten thousand times smaller than its radius, which indicates that the material in the disks is concentrated in dense clouds with roughly unit covering factor.
BIANCHI TYPE-II COSMOLOGICAL MODELS WITH CONSTANT DECELERATION PARAMETER
Authors: SINGH C. P. , KUMAR SURESH
Published: May 2006

A special law of variation for Hubble's parameter in anisotropic space–time models that yields a constant value of the deceleration parameter is presented. Also, a spatially homogeneous and anisotropic but locally rotationally symmetric (LRS) Bianchi type-II cosmological model is studied with a perfect fluid and constant deceleration parameter. Assuming the equation of state p = γρ, where 0≤γ≤1, and using a special law of variation for the Hubble parameter, we are able to construct many new solutions to Einstein's field equations of LRS Bianchi type-II for four different physical models (dust, radiation, Zel'dovich and vacuum). We discuss the solutions with power-law and exponential expansion and examine a particular class of models. A detailed study of kinematic, geometrical and observational properties is carried out.
THE RELATION BETWEEN OPTICAL POLARIZATION AND BEAMING EFFECT FOR BLAZARS
Authors: XIE Z. H. , CHEN L. E. , DU L. M. , MAO L. S.
Published: May 2006

On the basis of the beaming model, we have derived a relation between the observed polarization (P ob ) and the observed magnitude (m ob ), log P ob = -0.4(k-1)m ob +C, which indicates that the observed polarization is anti-correlated with the observed magnitude. Making use of the optical data of polarization and magnitude observed simultaneously for 47 blazars, we found that there is a significant anti-correlation between the observed polarization and the observed magnitude in the V-band, the linear regression equation of which is [Formula: see text], with the correlation coefficient of γ = -0.4537 and the chance probability of p = 1.360×10-3. Obviously, the statistical results are consistent with the theoretical results derived by the beaming model. Our results of both theory and statistical analysis of the data observed simultaneously are consistent with the observations of 3C345, Mrk421.

In addition, using these data, we have also analyzed the relation between the maximum optical polarization ([Formula: see text] in the V-band) and the maximum infrared polarization ([Formula: see text] in the H-band). For 20 objects with both the maximum optical and infrared polarization, a linear regression analysis gives a strong correlation of [Formula: see text], with a correlation coefficient of γ = 0.9071 and a chance probability of p < 1.0 ×10-4. The results suggest that both the infrared and optical emissions of blazars originate from the synchrotron radiation.
BRANE WORLD DYNAMICS AND ADIABATIC MATTER CREATION
Authors: GOPAKUMAR P. , VIJAYAGOVINDAN G. V.
Published: May 2006

We treat the adiabatic matter creation process in various three-brane models by applying the thermodynamics of open systems. The matter creation rate is found to affect the evolution of the scale factor and energy density of the universe. We find a modification at the early stages of cosmic dynamics. In GB and RS brane worlds, by choosing appropriate parameters we obtain the standard scenario, while the warped DGP model has different solutions. During later stages, since matter creation is negligible, the evolution reduces to FRW expansion, in the RS and GB models.
FRACTIONAL DEGREE VORTICES FOR A SPINOR GINZBURG–LANDAU MODEL
Authors: ALAMA STAN , BRONSARD LIA
Published: May 2006

Recent papers in the physics literature have introduced spin-coupled (or spinor) Ginzburg–Landau models for complex vector-valued order parameters in order to account for ferromagnetic or antiferromagnetic effects in high-temperature superconductors and in optically confined Bose–Einstein condensates. In this paper, we show that such models give rise to new types of vortices, with fractional degree and nontrivial core structure. We illustrate the various possibilites with some specific examples of Dirichlet problems in the unit disk.
PRESCRIBED HORIZONTAL AND VERTICAL TREES PROBLEM OF QUADRATIC DIFFERENTIALS
Authors: AU THOMAS KWOK-KEUNG , WAN TOM YAU-HENG
Published: May 2006

A sufficient condition for the existence of holomorphic quadratic differential on a non-compact simply-connected Riemann surface with prescribed horizontal and vertical trees is obtained. In particular, for any pair of complete ℝ-trees of finite vertices with (n + 2) infinite edges, there exists a polynomial quadratic differential on ℂ of degree n such that the associated vertical and horizontal trees are isometric to the given pair.
Cardiac excitation-contraction coupling is altered in myocytes from aged male mice but not in cells from aged female mice
Authors: Grandy Scott A. , Howlett Susan E.
Published: May 2006

This study characterized age-related alterations in excitation-contraction (EC)-coupling in ventricular myocytes and investigated whether these alterations are affected by the sex of the animal. Voltage-clamp experiments were conducted in myocytes from young adult (∼7 mo) and aged (∼24 mo) male and female mice. Intracellular Ca2+ concentrations and unloaded cell shortening were measured at 37°C with fura-2 and a video edge detector. Fractional shortening and Ca2+ current density were significantly reduced in aged male myocytes compared with those in young adult male cells. In addition, Ca2+ transients were significantly smaller in aged male myocytes. Sarcoplasmic reticulum (SR) content, assessed by rapid application of 10 mM caffeine, declined with age in male myocytes. However, EC coupling gain and fractional release of SR Ca2+ were similar in young adult and aged male cells. In contrast to results in male animals, fractional shortening and Ca2+ current densities were similar in young adult and aged myocytes isolated from female hearts. Furthermore, Ca2+ transient amplitudes were unaffected by age in female cells. Interestingly, SR Ca2+ content was elevated in aged female myocytes, and fractional SR Ca2+ release declined with age in females. However, the gain of EC coupling was not different in myocytes from young adult and aged female mice. These data demonstrate that age-related alterations in EC coupling are more prominent in myocytes from male hearts than in cells from female hearts and suggest that it is important to consider sex as a variable in studies of the effects of aging on cardiac EC coupling.
Resistance to pressure-induced dilatation in femoral but not saphenous artery: physiological role of latch?
Authors: Call Christopher , Han Shaojie , Speich John E. , Eddinger Thomas J. , Ratz Paul H.
Published: May 2006

We recently determined that the ability of the femoral artery (FA) to maintain higher levels of tonic isometric stress compared with the saphenous artery (SA) was due to differential expression of motor proteins permitting latch-bridge formation in FA and not SA. Arteries under pressure in vivo are not constrained to contract isometrically. Thus the significance of latch-bridge formation in arterial physiology remains to be determined. To address this translational question, diameter changes of pressurized FA and SA were compared. The reduction in lumen diameter induced by KCl at 80 mmHg (isobaric active constriction; IAC) was greater at 30 s than 10 min in SA. In FA, the reverse was true, mimicking isometric contractile responses identified in our earlier work. From 80 to 150 mmHg, the %IAC induced by KCl was greater in SA than FA (e.g., ∼80% vs. ∼30% at 120 mmHg). This was not explained by differences in contractile mechanisms but was likely due to differences in absolute artery diameters. In constricted arteries subjected to a ramp increase in pressure from 60 to 120 mmHg, the constricted diameter of FA, but not SA, was greater than the IAC diameter at each pressure. Thus FA but not SA could maintain a smaller diameter on being pressurized when first constricted than it could achieve by isobaric constriction. These data support the hypothesis that latch bridges permit constricted large-diameter elastic arteries such as the FA to temporarily resist dilatation in the face of transient increases in blood pressures.
Insulin induces myocardial protection and Hsp70 localization to plasma membranes in rat hearts
Authors: Li Gefeng , Ali Imtiaz S. , Currie R. William
Published: May 2006

Insulin induces the expression of the 70-kDa heat shock protein (Hsp70) in rat hearts. In this study, we examined insulin- and heat shock-treated hearts for improved contractile recovery after 30 min of ischemia, activation of the heat shock transcription factor, and localization of the Hsp70 in relation to dystrophin and α-tubulin. Adult male Sprague-Dawley rats were assigned to groups: 1) control, 2) sham control, 3) insulin injected (200 μU/g body wt), 4) heat shock treated (core body temperature 42°C for 15 min), and 5) heat shock and insulin treated. Six hours later, hearts were isolated for Langendorff perfusion to determine cardiac function, or myocardial tissues were collected and prepared for either electrophoretic mobility shift assay, Western blot analysis, or immunofluorescence microscopy. Insulin treatment with 6 h of recovery enhances postischemic myocardial recovery of contractile function and increases Hsp70 expression through activation of the heat shock transcription factor. Insulin-treated hearts had elevated levels of Hsp70, particularly in the membrane fraction. In contrast, heat-shocked hearts had elevated levels of Hsp70 in the cytosol, membrane, and pellet fractions. After insulin treatment, Hsp70 was mostly colocalized to the plasma membrane with dystrophin. In contrast, after heat shock, Hsp70 was localized mostly between cardiomyocytes in apparent vascular or perivascular elements. The localization of Hsp70 is dependent on the inducing stimuli of either heat shock or insulin treatment. The cell membrane versus vascular localization of Hsp70 suggests the interesting possibility of functionally distinct roles for Hsp70 in the heart, whether induced by insulin or heat shock treatment.
Cardioprotective effects of acute and chronic opioid treatment are mediated via different signaling pathways
Authors: Peart Jason N. , Gross Garrett J.
Published: May 2006

A 5-day exposure to morphine exerts a profound cardioprotective phenotype in murine hearts. In the present study, we examined mechanisms by which morphine generates this effect, exploring the roles of Giand Gsproteins, PKA, PKC, and β-adrenergic receptors (β-AR) in acute and chronic opioid preconditioning. Langendorff-perfused hearts from placebo, acute morphine (AM; 10 μmol/l)-, or chronic morphine (CM)-treated mice (75-mg pellet, 5 days) underwent 25-min ischemia and 45-min reperfusion. After reperfusion, placebo-treated hearts exhibited marked contractile and diastolic dysfunction [rate-pressure product (RPP), 40 ± 4% baseline; end-diastolic pressure (EDP), 33 ± 3 mmHg], whereas AM hearts showed significant improvement in recovery of RPP and EDP (60 ± 3% and 23 ± 4 mmHg, respectively; P < 0.05 vs. placebo). Furthermore, CM hearts demonstrated a complete return of diastolic function and significantly greater recovery of contractile function (83 ± 3%, P < 0.05 vs. both placebo and AM). Pretreatment with Giprotein inhibitor pertussis toxin abolished AM protection while partially attenuating CM recovery ( P < 0.05 vs. placebo). Treatment with Gsinhibitor NF-449 did not affect AM preconditioning yet completely abrogated CM preconditioning. Similarly, PKA inhibition significantly attenuated the ischemia-tolerant state afforded by CM, whereas it was ineffective in AM hearts. PKC inhibition with chelerythrine was ineffective in CM hearts while completely abrogating AM preconditioning. Moreover, whereas β1-AR blockade with CGP-20712A failed to alter recovery in CM hearts, the β2-AR antagonist ICI-118,551 significantly attenuated postischemic recovery. These data describe novel findings whereby CM preconditioning is mediated by a PKC-independent pathway involving PKA, β2-AR, and Gsproteins, whereas AM preconditioning is mediated via Giproteins and PKC.
Diastolic ventricular-vascular stiffness and relaxation relation: elucidation of coupling via pressure phase plane-derived indexes
Authors: Chung Charles S. , Strunc Audrey , Oliver Rachel , Kovács Sándor J.
Published: May 2006

Because systole and diastole are coupled and systolic ventricular-vascular coupling has been characterized, we hypothesize that diastolic ventricular-vascular coupling (DVVC) exists and can be characterized in terms of relaxation and stiffness. To characterize and elucidate DVVC mechanisms, we introduce time derivative of pressure (dP/d t) vs. time-varying pressure [P( t)] (pressure phase plane, PPP)-derived analogs of ventricular and vascular “stiffness” and relaxation parameters. Although volume change (dV) = 0 during isovolumic periods, and time-varying left ventricular (LV) stiffness, typically expressed as change in pressure per unit change in volume (dP/dV), is undefined, our formulation allows determination of a PPP-derived stiffness analog during isovolumic contraction and relaxation. Similarly, an aortic stiffness analog is also derivable from the PPP. LV relaxation was characterized via τ, the time constant of isovolumic relaxation, and vascular (aortic pressure decay) relaxation was characterized in terms of its equivalent (windkessel) exponential decay time constant κ. The results show that PPP-derived systolic and diastolic ventricular and vascular stiffness are strongly coupled [Formula: see text]. In support of the DVVC hypothesis, a strong linear correlation between relaxation (rate of pressure decay) indexes κ and τ (κ = 9.89τ − 90.3, r = 0.81) was also observed. The correlations observed underscore the role of long-term, steady-state DVVC as a diastolic function determinant. Awareness of the PPP-derived DVVC parameters provides insight into mechanisms and facilitates quantification of arterial stiffening and associated increase in diastolic chamber stiffness. The PPP method provides a tool for quantitative assessment and determination of the functional coupling of the vasculature to diastolic function.
First molecular evidence that inositol trisphosphate signaling contributes to infarct size reduction with preconditioning
Authors: Przyklenk Karin , Maynard Michelle , Whittaker Peter
Published: May 2006

Considerable attention has focused on the role of protein kinase C (PKC) in triggering the profound infarct-sparing effect of ischemic preconditioning (PC). In contrast, the involvement of inositol 1,4,5-trisphosphate [Ins( 1 , 4 , 5 )P3], the second messenger generated in parallel with the diacylglycerol-PKC pathway, remains poorly understood. We hypothesized that, if Ins( 1 , 4 , 5 )P3signaling [i.e., release of Ins( 1 , 4 , 5 )P3and subsequent binding to Ins( 1 , 4 , 5 )P3receptors] contributes to PC-induced cardioprotection, then the reduction of infarct size achieved with PC would be attenuated in mice that are deficient in Ins( 1 , 4 , 5 )P3receptor protein. To test this concept, hearts were harvested from 1) B6C3Fe- a/a-Itpr-1opt+/−/J mutants displaying reduced expression of Ins( 1 , 4 , 5 )P3receptor-1 protein, 2) Itpr-1opt+/+wild types from the colony, and 3) C57BL/6J mice. All hearts were buffer-perfused and randomized to receive two 5-min episodes of PC ischemia, pretreatment with d- myo-Ins( 1 , 4 , 5 )P3[sodium salt of native Ins( 1 , 4 , 5 )P3], the mitochondrial ATP-sensitive K+channel opener diazoxide, or no intervention (controls). After the treatment phase, all hearts underwent 30-min global ischemia followed by 2 h of reperfusion, and infarct size was delineated by tetrazolium staining. In both wild-type and C57BL/6J cohorts, area of necrosis in hearts that received PC, d- myo-Ins( 1 , 4 , 5 )P3, and diazoxide averaged 28–35% of the total left ventricle (LV), significantly smaller than the values of 52–53% seen in controls ( P < 0.05). In contrast, in Itpr-1opt+/−mutants, protection was only seen with diazoxide: neither PC nor d- myo-Ins( 1 , 4 , 5 )P3limited infarct size (52–58% vs. 56% of the LV in mutant controls). These data provide novel evidence that Ins( 1 , 4 , 5 )P3signaling contributes to infarct size reduction with PC.
Effects of diet-induced obesity on inflammation and remodeling after myocardial infarction
Authors: Thakker Geeta D. , Frangogiannis Nikolaos G. , Bujak Marcin , Zymek Paul , Gaubatz John W. , Reddy Anilkumar K. , Taffet George , Michael Lloyd H. , Entman Mark L. , Ballantyne Christie M.
Published: May 2006

Epidemiological studies indicate that obesity, insulin resistance, and diabetes are important comorbidities of patients with ischemic heart disease and increase mortality and development of congestive heart failure after myocardial infarction. Although ob/ob and db/db mice are commonly used to study obesity with insulin resistance or diabetes, mutations in the leptin gene or its receptor are rarely the cause of obesity in humans, which is, instead, primarily a consequence of dietary and lifestyle factors. Therefore, we used a murine model of diet-induced obesity to examine the physiological effects of obesity and the inflammatory and healing response of diet-induced obese (DIO) mice after myocardial ischemia-reperfusion injury. DIO mice developed hyperinsulinemia and insulin resistance and hepatic steatosis, with significant ectopic lipid deposition in the heart and cardiac hypertrophy in the absence of significant changes in blood pressure. The mRNA levels of chemokines at 24 h and cytokines at 24 and 72 h of reperfusion were higher in DIO than in lean mice. In granulation tissue at 72 h of reperfusion, macrophage density was significantly increased, whereas neutrophil density was reduced, in DIO mice compared with lean mice. At 7 days of reperfusion, collagen deposition in the scar was significantly reduced and left ventricular (LV) dilation and cardiac hypertrophy were increased, indicative of adverse LV remodeling, in infarcted DIO mice. Characterization of a murine diet-induced model of obesity and insulin resistance that satisfies many aspects commonly observed in human obesity allows detailed examination of the adverse cardiovascular effects of diet-induced obesity at the molecular level.
Characterization of right ventricular function after monocrotaline-induced pulmonary hypertension in the intact rat
Authors: Hessel Marleen H. M. , Steendijk Paul , den Adel Brigit , Schutte Cindy I. , van der Laarse Arnoud
Published: May 2006

We characterized hemodynamics and systolic and diastolic right ventricular (RV) function in relation to structural changes in the rat model of monocrotaline (MCT)-induced pulmonary hypertension. Rats were treated with MCT at 30 mg/kg body wt (MCT30, n = 15) and 80 mg/kg body wt (MCT80, n = 16) to induce compensated RV hypertrophy and RV failure, respectively. Saline-treated rats served as control (Cont, n = 13). After 4 wk, a pressure-conductance catheter was introduced into the RV to assess pressure-volume relations. Subsequently, rats were killed, hearts and lungs were rapidly dissected, and RV, left ventricle (LV), and interventricular septum (IVS) were weighed and analyzed histochemically. RV-to-(LV + IVS) weight ratio was 0.29 ± 0.05 in Cont, 0.35 ± 0.05 in MCT30, and 0.49 ± 0.10 in MCT80 ( P < 0.001 vs. Cont and MCT30) rats, confirming MCT-induced RV hypertrophy. RV ejection fraction was 49 ± 6% in Cont, 40 ± 12% in MCT30 ( P < 0.05 vs. Cont), and 26 ± 6% in MCT80 ( P < 0.05 vs. Cont and MCT30) rats. In MCT30 rats, cardiac output was maintained, but RV volumes and filling pressures were significantly increased compared with Cont (all P < 0.05), indicating RV remodeling. In MCT80 rats, RV systolic pressure, volumes, and peak wall stress were further increased, and cardiac output was significantly decreased (all P < 0.05). However, RV end-systolic and end-diastolic stiffness were unchanged, consistent with the absence of interstitial fibrosis. MCT-induced pressure overload was associated with a dose-dependent development of RV hypertrophy. The most pronounced response to MCT was an overload-dependent increase of RV end-systolic and end-diastolic volumes, even under nonfailing conditions.
Allicin in garlic protects against coronary endothelial dysfunction and right heart hypertrophy in pulmonary hypertensive rats
Authors: Sun Xiaowei , Ku David D.
Published: May 2006

We recently reported that coronary endothelial cell (CEC) dysfunction may contribute to the development of right ventricular (RV) hypertrophy (RVH) in monocrotaline (MCT)-induced pulmonary hypertensive rats. This present study investigated whether preservation of CEC function with garlic and its active metabolite allicin could abrogate RVH. Rats were fed with 1% raw garlic (RG)-supplemented diet 1 day or 3 wk before and 1 day after MCT injection, and changes in RV pressure (RVP), RVH, and CEC function were assessed 3 wk after MCT administration. In all cases, RG feeding significantly inhibited the development of RVP and RVH in these MCT rats. However, similar treatments with either boiled garlic (BG) or aged garlic (AG), which do not contain the active allicin metabolite, were ineffective. CEC function, assessed with acetylcholine-induced dilation as well as Nω-nitro-l-arginine methyl ester-induced constriction, revealed marked attenuation in right, but not left, coronary arteries of the MCT rats. This is consistent with our earlier report. Feeding of RG, but not BG or AG, preserved the CEC function and prevented the exaggerated vasoconstrictory responses of the MCT coronary arteries. There was no change in the coronary dilatory responses to a nitric oxide donor sodium nitroprusside. Further testings of vasoactivity to garlic extracts showed that only RG, but not BG or AG, elicited a potent, dose-dependent dilation on the isolated coronaries. Taken together, these findings show that the protective effect of garlic against the development of RVP and RVH in MCT-treated rats is probably mediated via its active metabolite allicin action on coronary endothelial function and vasoreactivity.
Transport in rat vessel walls. I. Hydraulic conductivities of the aorta, pulmonary artery, and inferior vena cava with intact and denuded endothelia
Authors: Shou Yixin , Jan Kung-ming , Rumschitzki David S.
Published: May 2006

In this study, filtration flows through the walls of the rat aorta, pulmonary artery (PA), and inferior vena cava (IVC), vessels with very different susceptibilities to atherosclerosis, were measured as a function of transmural pressure (ΔP), with intact and denuded endothelium on the same vessel. Aortic hydraulic conductivity ( Lp) is high at 60 mmHg, drops ∼40% by 100 mmHg, and is pressure independent to 140 mmHg. The trends are similar in the PA and IVC, dropping 42% from 10 to 40 mmHg and flat to 100 mmHg (PA) and dropping 33% from 10 to 20 mmHg and essentially flat to 60 mmHg (IVC). Removal of the endothelium renders Lp(ΔP) flat: it increases Lpof the aorta by ∼75%, doubles Lpof the PA, and quadruples Lpof the IVC. Specific resistance (1/ Lp) of the aortic endothelium is ∼47% of total resistance; i.e., the endothelium accounts for ∼47% of the ΔP drop at 100 mmHg. The PA value is 55% at >40 mmHg, and the IVC value is 23% at 10 mmHg. Lpof the intact aorta, PA, and IVC are order 10−8,10−7, and 5 × 10−7cm·s−1·mmHg−1, and wall thicknesses are 145.8 μm (SD 9.3), 78.9 μm (SD 3.3), and 66.1 μm (SD 4.1), respectively. These data are consistent with the different wall structures of the three vessels. The rat aortic Lpdata are quantitatively consistent with rabbit Lp(ΔP) (Tedgui A and Lever MJ. Am J Physiol Heart Circ Physiol 247: H784–H791, 1984; Baldwin AL and Wilson LM. Am J Physiol Heart Circ Physiol 264: H26–H32, 1993), suggesting that intimal compression under pressure loading may also play a role in Lp(ΔP) in these other vessels. Despite very different driving ΔP, nominal transmural water fluxes of these three vessels are very similar and, therefore, cannot alone account for their differences in disease susceptibility. The different fates of macromolecular tracers convected by these water fluxes into the walls of these vessels may account for this difference.
Enhanced isoproterenol-induced cardiac hypertrophy in transgenic rats with low brain angiotensinogen
Authors: Campos Luciana A. , Iliescu Radu , Fontes Marco Antonio Peliky , Schlegel Wolfgang-Peter , Bader Michael , Baltatu Ovidiu C.
Published: May 2006

We have previously shown that a permanent deficiency in the brain renin-angiotensin system (RAS) may increase the sensitivity of the baroreflex control of heart rate. In this study we aimed at studying the involvement of the brain RAS in the cardiac reactivity to the β-adrenoceptor (β-AR) agonist isoproterenol (Iso). Transgenic rats with low brain angiotensinogen (TGR) were used. In isolated hearts, Iso induced a significantly greater increase in left ventricular (LV) pressure and maximal contraction (+dP/d tmax) in the TGR than in the Sprague-Dawley (SD) rats. LV hypertrophy induced by Iso treatment was significantly higher in TGR than in SD rats (in g LV wt/100 g body wt, 0.28 ± 0.004 vs. 0.24 ± 0.004, respectively). The greater LV hypertrophy in TGR rats was associated with more pronounced downregulation of β-AR and upregulation of LV β-AR kinase-1 mRNA levels compared with those in SD rats. The decrease in the heart rate (HR) induced by the β-AR antagonist metoprolol in conscious rats was significantly attenuated in TGR compared with SD rats (−9.9 ± 1.7% vs. −18.1 ± 1.5%), whereas the effect of parasympathetic blockade by atropine on HR was similar in both strains. These results indicate that TGR are more sensitive to β-AR agonist-induced cardiac inotropic response and hypertrophy, possibly due to chronically low sympathetic outflow directed to the heart.
Congenital Hyperreninemic Hypoaldosteronism in Israel: Sequence Analysis of CYP11B2 Gene
Authors: Leshinsky-Silver Esther , Landau Zohar , Unlubay Sema , Bistrizer Tzvy , Zung Amnon , Tenenbaum-Rakover Yardena , DeVries Liat , Lev Dorit , Hanukoglu Aaron
Published: May 2006

Background/Aims: Isolated aldosterone biosynthesis defect causing congenital hyperreninemic hypoaldosteronism with otherwise normal adrenal function usually results from aldosterone synthase deficiency. Patients present with manifestations of mineralocorticoid deficiency during the first weeks of life. The largest numbers of cases have been described in Iranian Jews, who carried concomitantly two homozygous missense mutations (R181W and V386A). In a few cases with presumed aldosterone synthase deficiency no mutations in CYP11B2 gene have been identified. We describe a molecular and endocrine evaluation of seven cases of congenital hyperreninemic hypoaldosteronism in Israel. Patients/Methods: Two of the six Jewish patients are of Iranian origin. The parents of five other patients originated from Yemen, Syria and Morocco. One patient is a Muslim-Arab. CYP11B2’s exons, exon–intron boundaries and promoter region were sequenced by multiple PCR amplifications. Gene size determination was performed either by long-range PCR or by Southern blot analysis. Results: Only two patients (Iranian Jews) carried a known homozygous R181W, V386A mutations, other two were compound heterozygotes for either the R181W or V386A and one additional novel amino acid substitution (A319V or D335G), and one patient was found to be a carrier of the two novel variations (A319V and D335G). We could not find a molecular defect in 2 patients: one was a carrier of the D335G mutation and the other had no detectable molecular change in the coding and promoter regions. Conclusion: The genetic and molecular basis of congenital hyperreninemic hypoaldosteronism is more heterogeneous than previously described. The significance of amino acid substitutions identified in this study remains to be determined.
Molecular Pathogenetics of Renal Cancer
Authors: Skolarikos Andreas A. , Papatsoris Athanasios G. , Alivizatos Gerasimos , Deliveliotis Charalambos
Published: May 2006

Recent developments in genetics and molecular biology have led to an increased understanding of the pathobiology of renal cancer. Thorough knowledge of the molecular pathways associated with renal cancer is a prerequisite for novel potential therapeutic interventions. Studies are ongoing to evaluate novel anticancer agents that target specific molecular entities. This article reviews current knowledge on the genetics and molecular pathogenesis of sporadic and inherited forms of renal cancer.