bluuebunny/crossref_metadata_2025 huggingface dataset:
Diverse patterns of cell-specific gene expression in response to glucocorticoid in the developing small intestine
Authors: Yaylaoglu Murat B. , Agbemafle Barbara M. , Oesterreicher Thomas J. , Finegold Milton J. , Thaller Christina , Henning Susan J.
Published: July 2006

Although glucocorticoids are known to elicit functional maturation of the gastrointestinal tract, the molecular mechanisms of glucocorticoid action on the developing intestine have not been fully elucidated. Our previous microarray studies identified 66 transcripts as being rapidly induced in the jejunum following dexamethasone (Dex) administration to suckling mice. Now we report the specific cellular location of a subset of these transcripts. Mouse pups at P8 received Dex or vehicle and intestinal segments were collected 3–4 h later. Robotic-based in situ hybridization (ISH) was performed with digoxygenin-labeled riboprobes. Transcripts studied included Ndrg1, Sgk1, Fos, and two unknown genes ( Gene 9 and Gene 36). As predicted, ISH revealed marked diversity of cellular expression. In small intestinal segments, Sgk1 mRNA was in all epithelial cells; Fos mRNA was confined to epithelial cells at the villus tip; and Ndrg1 and Gene 36 mRNAs were localized to epithelial cells of the upper crypt and villus base. The remaining transcript ( Gene 9) was induced modestly in villus stroma and strongly in the muscle layers. In the colon, Ndrg1, Sgk1, and Gene 36 were induced in all epithelial cells; Gene 9 was in muscle layers only; and Fos was not detectable. For jejunal segments, quantitation of ISH signals in tissue from Dex-treated and vehicle-treated mice demonstrated mRNA increases very similar to those measured by Northern blotting. We conclude that glucocorticoid action in the intestine reflects diverse molecular mechanisms operating in different cell types and that quantitative ISH is a valuable tool for studying hormone action in this tissue.
Contributions of sustained INa and IKv43 to transmural heterogeneity of early repolarization and arrhythmogenesis in canine left ventricular myocytes
Authors: Flaim Sarah N. , Giles Wayne R. , McCulloch Andrew D.
Published: July 2006

The roles of sustained components of INa and IKv43 in shaping the action potentials (AP) of myocytes isolated from the canine left ventricle (LV) have not been studied in detail. Here we investigate the hypothesis that these two currents can contribute substantially to heterogeneity of early repolarization and arrhythmic risk. Quantitative data from voltage-clamp and expression profiling experiments were used to complete meaningful modifications to an existing “local control” model of canine midmyocardial myocyte excitation-contraction coupling for epicardial and endocardial cells. We include 1) heterogeneous IKv43, IKs, and ISERCA density; 2) modulation of IKv43 by Kv channel interacting protein type 2 (KChIP2) channel subunits; 3) a possible Ca2+-dependent open-state inactivation of IKv43; and 4) a sustained component of the inward Na+ current, INaL. The resulting simulations illustrate ways in which KChIP2- and Ca2+-dependent control of IKv43 can result in a sustained outward current that can neutralize INaL in a rate- and myocyte subtype-dependent manner. Both these currents appear to play significant roles in modulating AP duration and rate dependence in midmyocardial myocytes. Furthermore, an increased ratio of IKv43 to INaL is capable of protecting epicardial myocytes from the early afterdepolarizations resulting from the SCN5A-I1768V mutation-induced increase in INaL. Experimentally observed transmural differences in Ca2+ handling, including greater sarcoplasmic reticulum Ca2+ content and faster Ca2+ transient decay rates on the epicardium, were recapitulated in our simulations. By design, these models allow upward integration into organ models or may be used as a basis for further investigations into cellular heterogeneities.
Recombinant human VEGF treatment transiently increases lung edema but enhances lung structure after neonatal hyperoxia
Authors: Kunig Anette M. , Balasubramaniam Vivek , Markham Neil E. , Seedorf Gregory , Gien Jason , Abman Steven H.
Published: July 2006

Recent studies suggest that VEGF may worsen pulmonary edema during acute lung injury (ALI), but, paradoxically, impaired VEGF signaling contributes to decreased lung growth during recovery from ALI due to neonatal hyperoxia. To examine the diverse roles of VEGF in the pathogenesis of and recovery from hyperoxia-induced ALI, we hypothesized that exogenous recombinant human VEGF (rhVEGF) treatment during early neonatal hyperoxic lung injury may increase pulmonary edema but would improve late lung structure during recovery. Sprague-Dawley rat pups were placed in a hyperoxia chamber (inspired O2 fraction 0.9) for postnatal days 2–14. Pups were randomized to daily intramuscular injections of rhVEGF165 (20 μg/kg) or saline (controls). On postnatal day 14, rats were placed in room air for a 7-day recovery period. At postnatal days 3, 14, and 21, rats were killed for studies, which included body weight and wet-to-dry lung weight ratio, morphometric analysis [including radial alveolar counts (RAC), mean linear intercepts (MLI), and vessel density], and lung endothelial NO synthase (eNOS) protein content by Western blot analysis. Compared with room air controls, hyperoxia increased pulmonary edema by histology and wet-to-dry lung weight ratios at postnatal day 3, which resolved by day 14. Although treatment with rhVEGF did not increase edema in control rats, rhVEGF increased wet-to-dry weight ratios in hyperoxia-exposed rats at postnatal days 3 and 14 ( P < 0.01). Compared with room air controls, hyperoxia decreased RAC and increased MLI at postnatal days 14 and 21. Treatment with VEGF resulted in increased RAC by 181% and decreased MLI by 55% on postnatal day 14 in the hyperoxia group ( P < 0.01). On postnatal day 21, RAC was increased by 176% and MLI was decreased by 58% in the hyperoxia group treated with VEGF. rhVEGF treatment during hyperoxia increased eNOS protein on postnatal day 3 by threefold ( P < 0.05). We conclude that rhVEGF treatment during hyperoxia-induced ALI transiently increases pulmonary edema but improves lung structure during late recovery. We speculate that VEGF has diverse roles in hyperoxia-induced neonatal lung injury, contributing to lung edema during the acute stage of ALI but promoting repair of the lung during recovery.
Time-frequency coherence analysis of phrenic and hypoglossal activity in the decerebrate rat during eupnea, hyperpnea, and gasping
Authors: Marchenko Vitaliy , Rogers Robert F.
Published: July 2006

Fast respiratory rhythms include medium- (MFO) and high-frequency oscillations (HFO), which are much faster than the fundamental breathing rhythm. According to previous studies, HFO is characterized by high coherence (Coh) in phrenic (Ph) nerve activity, thereby providing a means of distinguishing between these two types of oscillations. Changes in Coh between the Ph and hypoglossal (XII) nerves during the transition from normal eupnic breathing to gasping have not been characterized. Experiments were performed on nine unanesthetized, chemo- and barodenervated, decerebrate adult rats, in which sustained asphyxia elicited hyperpnea and gasping. A gated time-frequency Coh analysis was developed and applied to whole Ph and medial XII nerve recordings. The results showed dynamic Ph-Ph Coh during eupnea, including MFO and HFO. XII-XII Coh during eupnea was broadband and included four distinct peaks, with low-frequency Coh dominating the epochs preceding the onset of Ph activity. During gasping, only MFO-peaks were present in Ph-Ph Coh. Bilateral XII activity showed a significant reduction in Coh and a shift toward lower frequencies during gasping. In contrast, contralateral Ph-XII Coh progressively increased during state changes from eupnea to gasping, a tendency mirrored in the startup part of the Ph activity. These data suggest significant hypoxia/hypercapnia-induced alterations in synchronization between respiratory outputs during the transition from eupnea to gasping, reflecting a reconfiguration of the respiratory network and/or alterations in the circuitry associated with the motor pools, including dynamic coupling between outputs.
Peripheral ghrelin deepens torpor bouts in mice through the arcuate nucleus neuropeptide Y signaling pathway
Authors: Gluck Elizabeth F. , Stephens Natalie , Swoap Steven J.
Published: July 2006

Many small mammals have the ability to enter torpor, characterized by a controlled drop in body temperature (Tb). We hypothesized that ghrelin would modulate torpor bouts, because torpor is induced by fasting in mice coincident with elevated circulating ghrelin. Female National Institutes of Health (NIH) Swiss mice were implanted with a Tb telemeter and housed at an ambient temperature (Ta) of 18°C. On fasting, all mice entered a bout of torpor (minimum Tb: 23.8 ± 2.0°C). Peripheral ghrelin administration (100 μg) during fasting significantly deepened the bout of torpor (Tb minimum: 19.4 ± 0.5°C). When the arcuate nucleus (ARC) of the hypothalamus, a ghrelin receptor-rich region of the brain, was chemically ablated with monosodium glutamate (MSG), fasted mice failed to enter torpor (minimum Tb = 31.6 ± 0.6°C). Furthermore, ghrelin administration had no effect on the Tb minimum of ARC-ablated mice (31.8 ± 0.8°C). Two major pathways that regulate food intake reside in the ARC, the anorexigenic α-melanocyte stimulating hormone (α-MSH) pathway and the orexigenic neuropeptide Y (NPY) signaling pathway. Both Ay mice, which have the α-MSH pathway blocked, and Npy −/− mice exhibited shallow, aborted torpor bouts in response to fasting (Tb minimum: 29.1 ± 0.6°C and 29.9 ± 1.2°C, respectively). Ghrelin deepened torpor in Ay mice (Tb minimum: 22.8 ± 1.3°C), but had no effect in Npy −/− mice (Tb minimum: 29.5 ± 0.8°C). Collectively, these data suggest that ghrelin's actions on torpor are mediated via NPY neurons within the ARC.
Changes in immune responses to oxidized LDL epitopes during aging in hypercholesterolemic apoE(−/−) mice
Authors: Dimayuga Paul C. , Zhao Xiaoning , Yano Juliana , Chyu Kuang-Yuh
Published: July 2006

Atherosclerosis is a disease associated with aging and is subject to modulation by both the innate and adaptive immune system. The time course of age-dependent changes in immune regulation in the context of atherosclerosis has not been characterized. This study aims to describe alteration of the immune responses to oxidized LDL (oxLDL) during aging that is associated with changes in plaque size and phenotype in apoE(−/−) mice. Mice fed a Western diet were euthanized at 15–17, 36, or >52 wk of age. The descending aortas were stained for assessment of extent of atherosclerosis. Plaque lipid, macrophage, and collagen content were evaluated in aortic sinus lesions. The adaptive immune response to oxLDL was assessed using anti-malondialdehyde-oxidized LDL (MDA-LDL) and copper-oxidized LDL (Cu-oxLDL) IgG, and the innate immune response was assessed using anti-Cu-oxLDL and phosphorylcholine (PC) IgM. Aging was associated with a significant increase in plaque area and collagen content and a decrease in plaque macrophage and lipid content. MDA-LDL IgG significantly increased at 36 wk but was reduced in mice >52 wk. Cu-oxLDL IgG increased with age and IgG-apoB immune complexes were increased in the >52 wk group. Cu-oxLDL and PC IgM significantly increased with age. The expression of splenic cytokines such as IFN-γ, IL-4, and IL-10 increased with age. Our study shows a generalized increase in innate immune responses associated with progression of atherosclerosis and a less inflammatory and less lipid-containing plaque phenotype during aging. The adaptive immune response appeared to be less generalized, with a specific reduction in MDA-LDL IgG.
Role of transthyretin in thyroxine transfer from cerebrospinal fluid to brain and choroid plexus
Authors: Kassem Nouhad A. , Deane Rashid , Segal Malcolm B. , Preston Jane E.
Published: July 2006

The transport of125I-labeled thyroxine (T4) from the cerebrospinal fluid (CSF) into brain and choroid plexus (CP) was measured in anesthetized rabbit [0.5 mg/kg medetomidine (Domitor) and 10 mg/kg pentobarbitonal sodium (Sagatal) iv] using the ventriculocisternal (V-C) perfusion technique.125I-labeled T4contained in artificial CSF was continually perfused into the lateral ventricles for up to 4 h and recovered from the cisterna magna. The %recovery of125I-labeled T4from the aCSF was 47.2 ± 5.6% ( n = 10), indicating removal of125I-labeled T4from the CSF. The recovery increased to 53.2 ± 6.3% ( n = 4) and 57.8 ± 14.8% ( n = 3), in the presence of 100 and 200 μM unlabeled-T4, respectively ( P < 0.05), indicating a saturable component to T4removal from CSF. There was a large accumulation of125I-labeled T4in the CP, and this was reduced by 80% in the presence of 200 μM unlabeled T4, showing saturation. In the presence of the thyroid-binding protein transthyretin (TTR), more125I-labeled T4was recovered from CSF, indicating that the binding protein acted to retain T4in CSF. However,125I-labeled T4uptake into the ependymal region (ER) of the frontal cortex also increased by 13 times compared with control conditions. Elevation was also seen in the hippocampus (HC) and brain stem. Uptake was significantly inhibited by the presence of endocytosis inhibitors nocodazole and monensin by > 50%. These data suggest that the distribution of T4from CSF into brain and CP is carrier mediated, TTR dependent, and via RME. These results support a role for TTR in the distribution of T4from CSF into brain sites around the ventricular system, indicating those areas involved in neurogenesis (ER and HC).
Muscle metabolic function and free-living physical activity
Authors: Hunter Gary R. , Larson-Meyer D. Enette , Sirikul Bovorn , Newcomer Bradley R.
Published: July 2006

We have previously shown that muscle metabolic function measured during exercise is related to exercise performance and subsequent 1-yr weight gain. Because it is well established that physical activity is important in weight maintenance, we examined muscle function relationships with free-living energy expenditure and physical activity. Subjects were 71 premenopausal black and white women. Muscle metabolism was evaluated by 31P magnetic resonance spectroscopy during 90-s isometric plantar flexion contractions (45% maximum). Free-living energy expenditure (TEE) was measured using doubly labeled water, activity-related energy expenditure (AEE) was calculated as 0.9 × TEE − sleeping energy expenditure from room calorimetry, and free-living physical activity (ARTE) was calculated by dividing AEE by energy cost of standard physical activities. At the end of exercise, anaerobic glycolytic rate (ANGLY) and muscle concentration of phosphomonoesters (PME) were negatively related to TEE, AEE, and ARTE ( P < 0.05). Multiple regression analysis showed that both PME (partial r = −0.29, <0.02) and ANGLY (partial r = −0.24, P < 0.04) were independently related to ARTE. PME, primarily glucose-6-phosphate and fructose-6-phosphate, was significantly related to ratings of perceived exertion ( r = 0.21, P ≤ 0.05) during a maximal treadmill test. PME was not related to ARTE after inclusion of RPE in the multiple regression model, suggesting that PME may be obtaining its relationship with ARTE through an increased perception of effort during physical activity. In conclusion, physically inactive individuals tend to be more dependent on anaerobic glycolysis during exercise while relying on a glycolytic pathway that may not be functioning optimally.
In vitro endothelial cell activation and inflammatory responses in end-stage heart failure
Authors: Hoare Ginette S. , Birks Emma J. , Bowles Christopher , Marczin Nandor , Yacoub Magdi H.
Published: July 2006

Background: vascular endothelial cell activation and dysfunction are observed in patients with severe heart failure and may contribute to systemic manifestations of this syndrome. It remains unknown whether inflammatory activation of these cells occurs in these patients because of increased circulating proinflammatory mediators. Aim: to determine whether the serum from patients with heart failure possesses a net proinflammatory bioactivity to active proinflammatory pathways in cultured endothelial cells. Methods: serum was obtained from stable patients with end-stage heart failure undergoing elective cardiac transplantation (Tx) and severely decompensated patients with heart failure requiring emergency left ventricular assist device (LVAD) implantation. Net proinflammatory bioactivity of serum was investigated by monitoring IκBα degradation and E-selectin expression in cultured human pulmonary artery endothelial cells (HPAEC) following incubation with serum samples. Serum cytokine concentrations were measured by ELISA and neutralizing antibodies were used to determine the role of specific factors in the observed bioactivity. Result: serum from both patient groups induced HPAEC IκBα degradation. Low basal HPAEC E-selectin expression significantly increased following treatment with Tx but not LVAD serum. Serum tumor necrosis factor-α (TNF-α) and IL-10 concentrations were higher in patients with LVAD than those with Tx, and soluble TNF-α receptor expression was high in both groups. Neither TNF-α nor IL-10 blocking experiments altered either bioassay result. Conclusion: activation of a specific profile of pro- and anti-inflammatory mediators is associated with heart failure resulting in HPAEC nuclear factor (NF)-κB activation. However, E-selectin expression is further regulated by unidentified factors. TNF-α is upregulated but appears to play no part in NFκB activation in these patients. These findings could have important therapeutic implications.
A Case of Chondrosarcoma Developing in a Recurrent Retroperitoneal Mass after Chemotherapy for Testicular Germ Cell Tumor
Authors: Assimakopoulos Stelios F. , Koutras Angelos , Ravazoula Panayiota , Makatsoris Thomas , Petsas Theodore , Iconomou Gregoris , Nikolopoulou Vassiliki , Kalofonos Haralabos P.
Published: July 2006

Teratomas with malignant transformation occur in a small proportion of patients with metastatic germ cell tumors treated with platinum-based chemotherapy. Chondrosarcoma has rarely been reported as a component of the second non-germ cell malignancy. We report the case of a 37-year-old man who developed a chondrosarcoma in a recurrent retroperitoneal mass after chemotherapy for testicular germ cell tumor. Malignant transformation of the retroperitoneal teratomatous mass occurred in the absence of any symptoms or clinical signs, elevation in serum tumor markers, or the presence of atypical elements in previously resected specimens, suggesting the need for close radiographic follow-up of these patients.
Intravesical Explosion during Transurethral Resection of Prostate – A Reminder
Authors: Srivastava Anand , Sandhu A.S. , Sinha T. , Madhusoodanan P. , Karan S.C. , Sethi G.S. , Talwar R. , Narang V.
Published: July 2006

Intravesical explosion during transurethral resection of the prostate (TURP) is an extremely rare but dreaded complication and results in rupture of the bladder. It is believed that intravesical explosion occurs due to formation of explosive gases in the bladder during TURP and its admixture with air. A case of intravesical explosion during TURP resulting in bladder rupture at our institution is described. Though the management of this catastrophe is relatively straightforward, it has the potential for dire consequences. We emphasize that, despite its rare occurrence, it is preventable and suggest measures to avoid it.
Laparoscopic Left Radical Nephrectomy and Hand-Assisted Isthmectomy of a Horseshoe Kidney with Renal Cell Carcinoma
Authors: Tobias-Machado M. , Massulo-Aguiar M.F. , Forseto, Jr. P.H. , Juliano R.V. , Wroclawski E.R.
Published: July 2006

A 64-year-old woman presented with recurrent gross hematuria and intermittent left-sided pain. A CT scan revealed an 8-cm mass in the left moiety of a horseshoe kidney. A laparoscopic transperitoneal approach was employed to control the vessels and release the left moiety of the kidney and a hand-assisted approach was performed for isthmectomy using compression of normal parenchyma and monopolar electrocautery. Additional sutures were applied externally in isthmus through hand-assisted incision to enhance hemostasis. The patient was discharged on postoperative day 4 with no complications and no relapse after a 1-year follow-up. We conclude that our technique is safe, cheap and effective for this complex clinical entity.
Production of Tense-Lax Contrast by Mandarin Speakers of English
Authors: Chen Yang
Published: July 2006

The spectral and temporal characteristics of three English tense-lax vowel pairs (/i-i/, /æ-Ε/, /u-u/) produced by native Mandarin speakers are reported. The euclidean distance based on first and second formant frequencies (F1 and F2), the durational differences, as well as the perceptual judgment of the tense-lax vowel contrast were examined in the syllable level productions of 40 Mandarin speakers compared to 40 American English speakers. Results of the comparative analysis indicated that Mandarin speakers differed significantly from the American English speakers in distinguishing the English tense/lax contrast. The general pattern shown across the Mandarin subjects was one in which the temporal feature, rather than the spectral feature, was more indicative of the tense-lax contrast as compared to the American speakers. In addition, the perception for the tense-lax contrast produced by Mandarin speakers was less distinctive as compared to the American speakers. The phonetic influences of the Mandarin language on the production of English tense-lax vowels are discussed.
Regression Tree Approach to Studying Factors Influencing Acoustic Voice Analysis
Authors: Deliyski Dimitar D. , Shaw Heather S. , Evans Maegan K. , Vesselinov Roumen
Published: July 2006

Multiple factors influence voice quality measurements (VQM) obtained during an acoustic voice assessment including: gender, intrasubject variability, microphone, environmental noise (type and level), data acquisition (DA) system, and analysis software. This study used regression trees to investigate the order and relative importance of these factors on VQM including interaction effects of the factors and how the outcome differs when the acoustic environment is controlled for noise. Twenty normophonic participants provided 20 voice samples each, which were recorded synchronously on five DA systems combined with six different microphones. The samples were mixed with five noise types at eight signal-to-noise ratio (SNR) levels. The resulting 80,000 audio samples were analyzed for fundamental frequency (F₀), jitter and shimmer using three software analysis systems: MDVP, PRAAT, and TF32 (CSpeech). Fifteen regression trees and their Variable Importance Measures were utilized to analyze the data. The analyses confirmed that all of the factors listed above were influential. The results suggest that gender, intrasubject variability, and microphone were significant influences on F₀. Software systems and gender were highly influential on measurements of jitter and shimmer. Environmental noise was shown to be the prominent factor that affects VQM when SNR levels are below 30 dB.
Prevalence of Stuttering in Regular and Special School Populations in Belgium Based on Teacher Perceptions
Authors: van Borsel John , Moeyaert Jozefien , Mostaert Charlotte , Rosseel Rijke , van Loo Evy , van Renterghem Tineke
Published: July 2006

The purpose of this study was to investigate stuttering prevalence in Flanders, the northern part of Belgium. Using questionnaires distributed among teachers, data were collected on 21,027 pupils from regular schools (age between 6 and 20 years) and 1,272 pupils attending special education (age between 6 and 15 years). The overall prevalence in the regular school population was 0.58%. It was 2.28% in the special school population. In agreement with past studies, stuttering prevalence was higher in males than in females, and higher in pupils attending special schools than in pupils from regular schools. The tendency for stuttering prevalence to decrease with increasing age was confirmed too, but not in the pupils of special schools. Additionally, the pupils of regular schools showed a pattern that was contrary to the general belief that the male-to-female ratio in stuttering prevalence increases with age. Results further indicate that the commonly cited stuttering prevalence figure of 1% is a generalization that requires interpretation.
FISH mapping of i(7q) in acute leukemias and myxoid liposarcoma reveals clustered breakpoints in 7p11.2: implications for formation and pathogenetic outcome of the idic(7)(p11.2)
Authors: Schaad K. , Strömbeck B. , Mandahl N. , Andersen M.K. , Heim S. , Mertens F. , Johansson B.
Published: July 2006

Isochromosome 7q – i(7q) – is seen in a wide variety of hematologic malignancies and solid tumors, often as a secondary change to a characteristic primary translocation. Despite its high frequency, nothing is known about the formation and the pathogenetic outcome of this abnormality. To address these issues, we performed a detailed fluorescence in situ hybridization (FISH) investigation of four acute lymphoblastic leukemias, one acute myeloid leukemia, and two myxoid liposarcomas with i(7q). Using FISH with bacterial artificial chromosomes (BACs) mapping between 7p12.2 and 7q11.2, the breakpoints (BPs) in all seven cases were shown to cluster to an approximately 340 kb segment at 7p11.2, covered by the overlapping BAC probes RP11-760D2 and RP11-10F11. Thus, the i(7q) should formally be designated idic(7) (p11.2). In one of the cases, FISH with fosmids could narrow down the BP further to an 80-kb sequence delineated by G248P81983A10 and G248P8793H7. No known genes are located in the 340-kb BP cluster region, indicating that the idic(7)(p11.2) does not result in a fusion or deregulation of genes in this segment. The pathogenetically important outcome is thus likely to be an altered gene expression because of copy number changes. The clustering of breakpoints might be due to frequent intrachromosomal duplicons in the BP region.
Differentiating sex chromosomes of the dioecious Spinacia oleracea L. (spinach) by FISH of 45S rDNA
Authors: Lan T. , Zhang S. , Liu B. , Li X. , Chen R. , Song W.
Published: July 2006

Spinacia oleracea L. (spinach) is a dioecious species with both male and female plants having 2n = 2x = 12 chromosomes, consisting of two large metacentrics, two long subtelocentrics, two short subtelocentrics, two acrocentrics, and four submetacentrics. The location of 45S rDNA was investigated on metaphase chromosomes using fluorescence in situ hybridization (FISH). The numbers of 45S rDNA foci in diploid sets of chromosomes from females was six and from males was five. All the fluorescent foci lay in secondary constrictions and the satellites. Our results indicate that an XY-type sex chromosome system could be present in spinach where the Y chromosome lacks a 45S RNA focus.
Two complementary recombinant chromosomes 5 in a healthy woman
Authors: Bartsch O. , Ergun M.A. , Balci S. , Kan D. , Eggermann T. , Kotzot D.
Published: July 2006

We report a healthy woman with two abortions who is a carrier for a rare heterozygous double recombinant of an inv(5) chromosome, karyotype 46,XX,rec(5)dup(5p) inv(5)(p13q22),rec(5)dup(5q)inv(5)(p13q22). Her father had a 46,XY,inv(5)(p13q22) karyotype; his consanguineous wife had died. Molecular investigation of 11 highly polymorphic markers spanning chromosome 5 revealed biparental inheritance for two markers (D5S406, D5S681) on 5p15.3 and 5q13.1, and an allele constellation not compatible with paternal heterodisomy for marker D5S623 on 5q11.2. Eight markers were not informative. Three mechanisms of formation are proposed: First, fertilization of a normal oocyte by a sperm carrying the two recombinant chromosomes 5, followed by postzygotic recombination between the normal maternal homologue and the rec(5)dup(5p), and by loss of the mitotically recombined maternal homologue, leading to segmental paternal heterodisomy 5q13→qter (trisomic rescue). Second, postzygotic recombination in a 46,XX,inv(5)(p13q22) zygote resulting in the 46,XX,rec(5)dup(5p)inv(5)(p13q22),rec(5) dup(5q)inv(5)(p13q22) karyotype, followed by absence of the original cell line in lymphocytes. Third and most likely, both parents were inv(5) carriers and complementary recombinations in maternal and paternal meiosis resulted in a zygote with two recombinant chromosomes 5. Our patient refused any further studies but later reported the birth of a phenotypically normal child. This is the first report known to us of complementation by two non-homologous recombinant chromosomes in a phenotypically normal woman, and the first example of a child born to a carrier of complementary recombinant chromosomes.
Outcome of Patients Undergoing Gamma Knife Stereotactic Radiosurgery for Medically Refractory Idiopathic Trigeminal Neuralgia: Medical College of Georgia’s Experience
Authors: Fountas Kostas N. , Lee Gregory P. , Smith Joseph R.
Published: July 2006

Gamma knife radiosurgery represents an established treatment option for the management of medically refractory trigeminal neuralgia (TN). In our current communication we present our experience in radiosurgically treating patients with idiopathic TN. Over a period of 5 years, 77 patients underwent gamma knife radiosurgery. The patients were divided into 2 groups based on their previous surgical treatment. In the group of patients with no previous surgeries, the initial response rate was 92.4% (48/52 patients), while in the group with previous surgeries it was 84% (21/25 patients). The excellent outcome rates (complete pain relief with no pain medications) at the completion of 1, 2 and 3 years after treatment for the group with no previous surgeries were: 80.8% (42/52 patients), 69.2% (36/52 patients) and 53.8% (28/52 patients), respectively. The respective excellent outcome rates for the group of patients with previous surgeries were: 64% (16/25 patients), 44% (11/25 patients) and 12% (3/25 patients). The good outcome rates at the completion of 1, 2 and 3 years after treatment for the group with no previous surgeries were: 7.7% (4/52 patients), 11.5% (6/52 patients) and 19.2% (10/52 patients). The respective percentages of good outcome for the patients with previous surgery were: 12% (3/25 patients) at 1 year, 16% (4/25 patients) at 2 years and 32% (8/25 patients) at the completion of 3 years after treatment. The most commonly encountered complication in our series was the development of facial numbness. Our findings confirm previous reports that the presence of preceding surgical interventions represents a negative long-term outcome factor. However, gamma knife radiosurgery constitutes a safe and efficient minimally invasive treatment option for patients with idiopathic TN.
Cell Cycle Inhibitory Protein p27 in Human Middle Ear Cholesteatoma
Authors: Kuczkowski Jerzy , Bakowska Alicja , Pawelczyk Tadeusz , Narozny Waldemar , Mikaszewski Boguslaw
Published: July 2006

Aim: To evaluate the immunohistochemical and molecular presentation of protein p27 in cholesteatoma. Methods: 42 cholesteatoma samples and 6 external ear canal skin (EECS) specimens were investigated and analyzed taking into consideration congenital, acquired, recurrent cholesteatoma, and EECS. Results: The expression of p27 was found in 16 (38.1%) out of 42 specimens of cholesteatoma and in 5 (83.3%) out of 6 specimens of EECS. There was a significant difference in p27-positive staining rate between EECS and cholesteatoma epithelium (p < 0.008). The presence of p27 was detected in 10 cases of acquired cholesteatoma, 2 cases of congenital and 3 cases of recurrent cholesteatoma. There was no significant difference between the presence of p27 in cholesteatoma and EECS (p = 0.01). Conclusion: The down-regulation of p27 is a key player in cell cycle control and plays an undefined role in the pathogenesis of all types of cholesteatoma.
Effect of Metabolite I of Erdosteine on the Release of Human Neutrophil Elastase
Authors: Braga Pier Carlo , Dal Sasso Monica , Culici Maria , Verducci Paola , Lo Verso Rosa , Marabini Laura
Published: July 2006

Erdosteine is a mucolytic drug whose metabolization gives rise to an active metabolite with an SH group (Met I), which reduces neutrophil release of reactive oxygen species and the peroxynitrite generated by the reaction of superoxide anion with nitric oxide, thus disrupting the phlogogenic loop sustained by activated neutrophils. Elastase, a serine proteinase released by activated human neutrophils, can degrade a wide variety of biomacromolecules including elastin and is considered to be pivotal in the pathogenesis of respiratory tract inflammation. The aim of this study was to examine whether, in addition to reducing the generation of free radicals, Met I can also interfere with the human neutrophil release of elastase. After the neutrophils were incubated with increasing amounts of Met I (1.25, 2.5, 5, 10, 20 µg/ml), elastase exocytosis was initiated by fMLP and measured using MeO-Suc-Ala-Ala-Pro-Val-MCA. The results showed that Met I significantly inhibits fMLP-induced elastase release by neutrophils in a concentration-dependent manner from 2.5 to 20 µg/ml. Our findings may be clinically relevant because the inhibitory effects were obtained at Met I concentrations that are achievable in the clinical setting. By reducing elastase and oxidant radical release (two major components of the inflammatory process), Met I have clinically useful anti-inflammatory effects.
The Prognostic Value of Initial Relapses on the Evolution of Disability in Patients with Relapsing-Remitting Multiple Sclerosis
Authors: Binquet C. , Quantin C. , Le Teuff G. , Pagliano J.F. , Abrahamowicz M. , Moreau T.
Published: July 2006

The evolution of multiple sclerosis (MS) and the resulting disability are unpredictable. To identify clinical variables that could be potential prognostic factors, we followed a cohort of 288 patients diagnosed as having relapsing-remitting MS between 1990 and 2003. The end point was the first occurrence of a non-reversible EDMUS-GS score ≧3 (moderate disability). The impact of the number of MS attacks during the first 2 years of the disease as well as the first interattack interval were assessed in two Cox models, one using a fixed-in-time covariate, the other using a time-dependent covariate. Older age at onset and a higher number of MS attacks during the first 2 years of MS proved to be predictors of unfavourable prognosis. The first interattack interval had no influence on the evolution of the disability, conversely to the first relapse which had a short-term impact on the prognosis. We confirmed that the age at onset and the number of MS attacks during the first 2 years of MS are predictors of the evolution of the disability and demonstrated the importance of using time-dependent covariates.
Prevention of Adhesion to Prosthetic Mesh in Incisional Ventral Hernias: Comparison of Different Barriers in an Experimental Model
Authors: Dilege E. , Coskun H. , Gündüz B. , Sakiz D. , Mihmanli M.
Published: July 2006

Background: The purpose of this study was to compare the intra-abdominal adhesion formation following ventral hernia repair by using oxidized regenerated cellulose (ORC) as a barrier underneath polypropylene mesh (PPM), and sodium hyaluronate/carboxymethylcellulose (HA/CMC)-coated PPM. Methods: A ventral abdominal defect was created in each of 30 male rats which were divided into three groups. In group 1 (control) the defect was repaired with PPM; in group 2 ORC was laid over the viscera and the defect was repaired with PPM, and in group 3 HA/CMC-coated PPM was used for the repairing procedure. On the 28th postoperative day all the rats were sacrificed and adhesions were evaluated by laparoscopic exploration followed by histopathological examination. Results: Animals treated with ORC and PPM, and HA/CMC-coated PPM showed significantly less adhesions than the control group (p = 0.026) and the intra-abdominal adhesions of the rats in these two groups were significantly easier to release than in the control group (p = 0.001). There was no significant difference between the ORC and HA/CMC groups. Conclusions: ORC used together with PPM is as effective as HA/CMC-coated PPM and ORC can be used as an adhesion barrier in intra-abdominal hernia repair.
Effects of Estrogen in the Male Rat Medial Amygdala: Infusion of an Aromatase Inhibitor Lowers Mating and Bovine Serum Albumin-Conjugated Estradiol Implants Do Not Promote Mating
Authors: Huddleston Gloria G. , Paisley Jacquelyn C. , Clancy Andrew N.
Published: July 2006

In male rats, copulatory behavior depends on estrogen-responsive neurons located in brain areas known to be crucial for mating. Blocking the aromatization of testosterone (T) to estradiol (E2) either throughout the brain or within the medial preoptic area (MPO) reduces mating, whereas E2 treatment of either the MPO or the medial amygdala (MEA) maintains sexual behavior. The effects of T aromatization in the MEA have received less attention; therefore, 2 studies were done to further elucidate the effects of E2 in the MEA. In experiment 1, gonadally intact male rats that showed robust mating behavior were administered chronic fadrozole, a nonsteroidal aromatase inhibitor, to the MEA to stop the conversion of T to E2 and then paired with receptive females. Infusion of fadrozole to the MEA significantly lowered mating behavior in experimental males compared to vehicle-infused control males. To further investigate the mechanism by which E2 acts in the MEA, in experiment 2, E2 conjugated to bovine serum albumin (BSA-E2: a complex of E2 and a large protein that does not cross the plasma membrane, thereby restricting the action of E2 to cell-surface signaling) was chronically administered bilaterally to the MEA of castrated, dihydrotestosterone-treated males. This treatment did not maintain mating behavior. These studies show that E2 acts in the MEA to promote male sexual behavior and suggest an intercellular mechanism of E2 action.
Color Doppler Ultrasonography in the Diagnostic Evaluation of Renal Allografts
Authors: Schwenger Vedat , Hinkel Ulrich Paul , Nahm Anna-Maria , Morath Christian , Zeier Martin
Published: July 2006

Color Doppler ultrasonography of large allograft vessels and renal parenchyma is established firmly in the diagnosis of renal allograft perfusion. While conventional color Doppler ultrasonography has proven itself to be an indispensable, rapid, highly valid and practicable method, e.g. in the diagnosis of allograft artery stenosis or allograft vein thrombosis, the diagnostic usefulness of this method with regard to allograft perfusion is considerably limited. With contrast-enhanced sonography, a simple and readily implementable method that enables the early diagnosis of chronic allograft nephropathy is now available. The timely diagnosis of vascular damage prior to a rise in S-creatinine offers the possibility of early therapeutic intervention and thus at least the potential for the improvement of allograft survival.
Chemokines and Incident Coronary Heart Disease
Authors: Herder Christian , Baumert Jens , Thorand Barbara , Martin Stephan , Löwel Hannelore , Kolb Hubert , Koenig Wolfgang
Published: July 2006

Objectives—

The chemokines monocyte chemoattractant protein-1 (MCP-1/CCL2), interleukin-8 (IL-8/CXCL8), and interferon-γ–inducible protein-10 (IP-10/CXCL10) have been reported to be involved in the development of atherosclerosis and type 2 diabetes. The aim of this study was to assess whether elevated systemic levels of these chemokines precede coronary events.

Methods and Results—

We investigated MCP-1, IL-8, and IP-10 serum levels in a case-cohort design based on data from 381 individuals (294 men, 87 women) with and 1977 individuals (1006 men, 971 women) without incident coronary heart disease (CHD) from the prospective, population-based MONICA/KORA Augsburg study (1984 to 2002). The mean follow-up time was 11.0 years. Baseline concentrations were significantly higher in cases compared with noncases (
P
≤0.001 for all chemokines). MCP-1 and IL-8 remained associated with CHD risk after adjustment for age, sex, and survey with hazard ratios (95% confidence intervals) comparing extreme tertiles of 1.39 (1.05 to 1.84) for MCP-1 and 1.48 (1.10 to 1.99) for IL-8. However, adjustment for further cardiovascular and immunologic risk factors attenuated the observed associations, and they became nonsignificant.

Conclusions—

Elevated systemic levels of the chemokines MCP-1, IL-8, and IP-10 precede CHD but do not represent independent risk factors. Thus, the associations are less pronounced than previously shown for type 2 diabetes.
FXR Deficiency Causes Reduced Atherosclerosis inLdlr−/−Mice
Authors: Zhang Yanqiao , Wang Xuping , Vales Charisse , Lee Florence Ying , Lee Hans , Lusis Aldons J. , Edwards Peter A.
Published: July 2006

Objective—Based on the observation thatFxr−/−mice exhibit a proatherogenic lipoprotein profile, we investigated the role of FXR in the development of atherosclerosis.

Methods and Results—Administration of a western diet toFxr−/−mice or wild-type mice does not result in the development of significant atherosclerotic lesions. Consequently we generatedFxr−/−Ldlr−/−(DKO) mice and compared lesion development withLdlr−/−mice. After 16 weeks on a Western diet,en faceanalysis of the aorta indicated that the male DKO mice had reduced atherosclerotic lesions as compared withLdlr−/−mice. Plasma low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels were reduced by 40% to 50%, whereas triglyceride levels increased 4-fold in the male DKO mice. Finally, peritoneal macrophages freshly isolated from male DKO mice had reduced expression of CD36 mRNA and decreased neutral lipid accumulation, as compared withLdlr−/−mice.

Conclusions—FXR deficiency in male, but not female,Ldlr−/−mice results in a reduction in the size of atherosclerotic lesions in the aorta. The reduction in atherosclerosis may result from a decrease in plasma low-density lipoprotein cholesterol, coupled with reduced expression of CD36 in macrophages of DKO mice.
High-Dose Atorvastatin Improves Hypercholesterolemic Coronary Endothelial Dysfunction Without Improving the Angiogenic Response
Authors: Boodhwani Munir , Nakai Yasunari , Voisine Pierre , Feng Jun , Li Jian , Mieno Shigetoshi , Ramlawi Basel , Bianchi Cesario , Laham Roger , Sellke Frank W.
Published: July 2006

Background—

Although 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) can restore endothelial function in coronary disease, in vitro and murine studies have shown their effects on myocardial angiogenesis to be biphasic and dose dependent. We investigated the functional and molecular effects of high-dose atorvastatin on the endogenous angiogenic response to chronic myocardial ischemia in hypercholesterolemic swine.

Methods and Results—

Yucatan pigs were fed either a normal (NORM group; n=7) or high-cholesterol diet, with (CHOL-ATR group; n=7) or without (CHOL group; n=6) atorvastatin (3 mg/kg per day) for 13 weeks. Chronic ischemia was induced by ameroid constrictor placement around the circumflex artery. Seven weeks later, microvessel relaxation responses, myocardial perfusion, and myocardial protein expression were assessed. The CHOL group demonstrated impaired microvessel relaxation to adenosine diphosphate (29±3% versus 61±6%, CHOL versus NORM;
P
<0.05), which was normalized in the CHOL-ATR group (67±2%;
P
=NS versus NORM). Collateral-dependent myocardial perfusion, adjusted for baseline, was significantly reduced in the CHOL group (−0.27±0.07 mL/min per gram versus NORM;
P
<0.001) as well as the CHOL-ATR group (−0.35±0.07 mL/min per gram versus NORM;
P
<0.001). Atorvastatin treatment was associated with increased phosphorylation of Akt (5.7-fold increase versus NORM;
P
=0.001), decreased vascular endothelial growth factor expression (−68±8%;
P
<0.001 versus NORM), and increased expression of the antiangiogenic protein endostatin (210±48%;
P
=0.004 versus NORM).

Conclusions—

Atorvastatin improves hypercholesterolemia-induced endothelial dysfunction without appreciable changes in collateral-dependent perfusion. Increased myocardial expression of endostatin, decreased expression of vascular endothelial growth factor, and chronic Akt activation associated with atorvastatin treatment may account for the diminished angiogenic response.
Counterpulsation From the Skeletal Muscle Ventricle and the Intraaortic Balloon Pump in the Normal and Failing Circulations
Authors: Ramnarine Ian R. , Capoccia Massimo , Ashley Zoe , Sutherland Hazel , Russold Michael , Summerfield Nuala , Salmons Stanley , Jarvis Jonathan C.
Published: July 2006

Background—

The intra-aortic balloon pump (IABP) is the device that is in most common use to provide cardiovascular support. A skeletal muscle ventricle (SMV) was configured to produce counterpulsation in the thoracic aorta similar to that obtained with an IABP. The hemodynamic effects of an IABP and a SMV in the same animal and in both normal and failing circulations were assessed.

Methods and Results—

SMVs were connected to and IABPs were placed in the thoracic aorta of 12 anesthetized pigs. Hemodynamic parameters during the IABP- or the SMV-assisted beat were compared with those during the preassist beat. Acute heart failure was induced in 6 of the pigs by snaring the left anterior descending coronary artery (LAD). The hemodynamic effects of the IABP and the SMV were then reassessed. In the assisted cycles, SMV activation increased the mean aortic diastolic pressure (MADP) by 26.5±3.5%, the mean diastolic LAD flow by 48.4±7.2%, and endocardial viability ratio (EVR) by 31.6±3.8% (
P
<0.0001). In the same animals, IABP assist increased MADP by 19.8±2.3%, mean diastolic LAD flow by 37.2±3.9%, and EVR by 21.4±3.0% (
P
<0.0001). Under acute heart failure conditions, both SMV and IABP assist significantly increased MADP, mean diastolic LAD flow, and EVR.

Conclusions—

In both the normal and failing circulations, the SMV was an effective counterpulsator, providing cardiac assist that was at least equal to that available from an IABP. The SMV may therefore provide the proven benefits of an IABP in ambulant patients.