bluuebunny/crossref_metadata_2025 huggingface dataset:
ADSORPTION OF POLYATOMICS: THEORETICAL APPROACHES IN MODEL SYSTEMS AND APPLICATIONS
Authors: RICCARDO JOSÉ L. , ROMÁ FEDERICO J. , RAMIREZ-PASTOR ANTONIO J.
Published: November 2006

The adsorption of polyatomics on one- and two-dimensional lattices is studied by combining theoretical modeling, Monte-Carlo (MC), simulations and their correspondence with experimental results. In one dimension, the rigorous statistical thermodynamics of interacting chains has been presented. With respect to two-dimensional adsorption, six different models to study non-interacting adsorbates have been discussed: (i) an extension to two dimensions of the exact thermodynamic functions obtained in one dimension; (ii) the Flory–Huggins's approximation and its modification to address linear adsorbates; (iii) the well-known Guggenheim–DiMarzio approximation; (iv) the fourth one is a new description of adsorption phenomena, based on Haldane's fractional statistics; (v) the so-called Occupation Balance, based on the expansion of the reciprocal of the fugacity; and (vi) a simple semi-empirical model obtained by combining exact one-dimensional calculations and Guggenheim–DiMarzio approach. In addition, the statistical thermodynamics of interacting polyatomics has been developed on a generalization in the spirit of the Bragg–Williams and the quasi-chemical approximations. Comparison with MC simulations and experimental adsorption isotherms are used to test the accuracy and reliability of the proposed models. Finally, applications to heterogeneous systems and multilayer adsorption are discussed.
Cloning, purification, and identification of the liver canalicular ecto-ATPase as NTPDase8
Authors: Fausther Michel , Lecka Joanna , Kukulski Filip , Lévesque Sébastien A. , Pelletier Julie , Zimmermann Herbert , Dranoff Jonathan A. , Sévigny Jean
Published: November 2006

Extracellular nucleotides regulate critical liver functions via the activation of specific transmembrane receptors. The hepatic levels of extracellular nucleotides, and therefore the related downstream signaling cascades, are modulated by cell-surface enzymes called ectonucleotidases, including nucleoside triphosphate diphosphohydrolase-1 (NTPDase1/CD39), NTPDase2/CD39L1, and ecto-5′-nucleotidase/CD73. The goal of this study was to determine the molecular identity of the canalicular ecto-ATPase/ATPDase that we hypothesized to correspond to the recently cloned NTPDase8. Human and rat NTPDase8 cDNAs were cloned, and the genes were located on chromosome loci 9q34 and 3p13, respectively. The recombinant proteins, expressed in COS-7 and HEK293T cells, were biochemically characterized. NTPDase8 was also purified from rat liver by Triton X-100 solubilization, followed by DEAE, Affigel Blue, and concanavalin A chromatographies. Importantly, NTPDase8 was responsible for the major ectonucleotidase activity in liver. The ion requirement, apparent Kmvalues, nucleotide hydrolysis profile, and preference as well as the resistance to azide were similar for recombinant NTPDase8s and both purified rat NTPDase8 and porcine canalicular ecto-ATPase/ATPDase. The partial NH2-terminal amino acid sequences of all NTPDase8s share high identity with the purified liver canalicular ecto-ATPase/ATPDase. Histochemical analysis showed high ectonucleotidase activities in bile canaliculi and large blood vessels of rat liver, in agreement with the immunolocalization of NTPDase1, 2, and 8 with antibodies developed for this study. No NTPDase3 expression could be detected in liver. In conclusion, NTPDase8 is the canalicular ecto-ATPase/ATPDase and is responsible for the main hepatic NTPDase activity. The canalicular localization of this enzyme suggests its involvement in the regulation of bile secretion and/or nucleoside salvage.
Taste Receptors in the Gastrointestinal Tract. IV. Functional implications of bitter taste receptors in gastrointestinal chemosensing
Authors: Sternini Catia
Published: November 2006

Changes in the luminal contents of the gastrointestinal tract modulate gastrointestinal functions, including absorption of nutrients, food intake, and protection against harmful substances. The current notion is that mucosal enteroendocrine cells act as primary chemoreceptors by releasing signaling molecules in response to changes in the luminal environment, which in turn activate nerve terminals. The recent discovery that taste receptors and G protein subunits α-gustducin and α-transducin, involved in gustatory signal transduction, are expressed in the gastrointestinal mucosa supports the concept of a chemosensory machinery in the gastrointestinal tract. An understanding of luminal sensing processes responsible for the generation of the appropriate functional response to specific nutrients and nonnutrients is of clinical importance since aberrant or unsteady responses to changes in luminal contents might result in disease states ranging from intoxication to feeding disorders and inflammation. The purpose of this theme article is to discuss the functional implications of bitter taste signaling molecules in the gastrointestinal tract deduced by their localization in selected populations of epithelial cells and their relationship with neural pathways responsible for the generation of specific responses to luminal contents.
Regulation of Triglyceride Metabolism. I. Eukaryotic neutral lipid synthesis: “Many ways to skin ACAT or a DGAT”
Authors: Turkish Aaron , Sturley Stephen L.
Published: November 2006

Esterification of sterols, fatty acids and other alcohols into biologically inert forms conserves lipid resources for many cellular functions. Paradoxically, the accumulation of neutral lipids such as cholesteryl ester or triglyceride, is linked to several major disease pathologies. In a remarkable example of genetic expansion, there are at least eleven acyltransferase reactions that lead to neutral lipid production. In this review, we speculate that the complexity and apparent redundancy of neutral lipid synthesis may actually hasten rather than impede the development of novel, isoform-specific, therapeutic interventions for acne, type 2 diabetes, obesity, hyperlipidemia, fatty liver disease, and atherosclerosis.
Lack of central nitric oxide triggers erectile dysfunction in diabetes
Authors: Zheng Hong , Bidasee Keshore R. , Mayhan William G. , Patel Kaushik P.
Published: November 2006

Erectile dysfunction is a serious and common complication of diabetes mellitus. The proposed mechanisms for erectile dysfunction in diabetes include central and autonomic neuropathy, endothelial dysfunction, and smooth muscle dysfunction. The paraventricular nucleus (PVN) of the hypothalamus is known to be involved in centrally mediated penile erection. This study was designed to examine the role of nitric oxide (NO) within the central nervous system component of the behavioral responses including erection in diabetic rats. N-methyl-d-aspartic acid (NMDA)-induced erection, yawning, and stretch through the PVN can be blocked by prior administration of NO synthase (NOS) blocker, l-NMMA, in freely moving, conscious male normal rats. Four weeks after streptozotocin (STZ) and vehicle injections, NMDA-induced erection, yawning, and stretch responses through the PVN are significantly blunted in diabetic rats compared with control rats. Examination of neuronal NOS (nNOS) protein by Western blot analysis indicated a reduced amount of nNOS protein in the PVN of rats with diabetes compared with control rats. Furthermore, restoring nNOS within the PVN by gene transfer using adenoviral transfection significantly restored the erectile and yawning responses to NMDA in diabetic rats. These data demonstrate that a blunted NO mechanism within the PVN may contribute to NMDA-induced erectile dysfunction observed in diabetes mellitus.
Monocyte chemoattractant protein-1 influences trauma-hemorrhage-induced distal organ damage via regulation of keratinocyte-derived chemokine production
Authors: Frink Michael , Lu Ailing , Thobe Bjoern M. , Hsieh Ya-Ching , Choudhry Mashkoor A. , Schwacha Martin G. , Kunkel Steven L. , Chaudry Irshad H.
Published: November 2006

Leukocyte infiltration, mediated by chemokines, is a key step in the development of organ dysfunction. Lung and liver neutrophil infiltration following trauma-hemorrhage is associated with upregulation of monocyte chemoattractant protein-1 (MCP-1). Because MCP-1 is not a major attractant for neutrophils, we hypothesized that MCP-1 influences neutrophil infiltration via regulation of keratinocyte-derived chemokines (KC). To study this, male C3H/HeN mice were pretreated with MCP-1 antiserum or control serum and subjected to trauma-hemorrhage or sham operation. Animals were killed 4 h after resuscitation. One group of trauma-hemorrhage mice receiving MCP-1 antiserum was also treated with murine KC during resuscitation. Plasma levels and tissue content of MCP-1 and KC were determined by cytometric bead arrays. Immunohistochemistry was performed to determine neutrophil infiltration; organ damage was assessed by edema formation. Treatment with MCP-1 antiserum significantly decreased systemic, lung, and liver levels of MCP-1 and KC following trauma-hemorrhage. This decrease in MCP-1 levels was associated with decreased neutrophil infiltration and edema formation in lung and liver following trauma-hemorrhage. Restitution of KC in mice treated with MCP-1 antiserum restored tissue neutrophil infiltration and edema. These results lead us to conclude that increased levels of MCP-1 cause neutrophil accumulation and distant organ damage by regulating KC production during the postinjury inflammatory response.
Accessory muscle activity contributes to the variation in time to task failure for different arm postures and loads
Authors: Rudroff Thorsten , Barry Benjamin K. , Stone Amy L. , Barry Carolyn J. , Enoka Roger M.
Published: November 2006

Time to failure and electromyogram activity were measured during two types of sustained submaximal contractions with the elbow flexors that required each subject to exert the same net muscle torque with the forearm in two different postures. Twenty men performed the tasks, either by maintaining a constant force while pushing against a force transducer (force task), or by supporting an equivalent load while maintaining a constant elbow angle (position task). The time to failure for the position task with the elbow flexed at 1.57 rad and the forearm horizontal was less than that for the force task (5.2 ± 2.6 and 8.8 ± 3.6 min, P = 0.003), whereas it was similar when the forearm was vertical (7.9 ± 4.1 and 7.8 ± 4.5 min, P = 0.995). The activity of the rotator cuff muscles was greater during the position tasks (25.1 ± 10.1% maximal voluntary contraction) compared with the force tasks (15.2 ± 5.4% maximal voluntary contraction, P < 0.001) in both forearm postures. However, the rates of increase in electromyogram of the accessory muscles and mean arterial pressure were greater for the position task only when the forearm was horizontal ( P < 0.05), whereas it was similar for the elbow flexors. These findings indicate that forearm posture influences the difference in the time to failure for the two fatiguing contractions. When there was a difference between the two tasks, the task with the briefer time to failure involved greater rates of increase in accessory muscle activity and mean arterial pressure.
Sarcopenic obesity and inflammation in the InCHIANTI study
Authors: Schrager Matthew A. , Metter E. Jeffrey , Simonsick Eleanor , Ble Alessandro , Bandinelli Stefania , Lauretani Fulvio , Ferrucci Luigi
Published: November 2006

The aging process is often paralleled by decreases in muscle and increases in fat mass. At the extreme these two processes lead to a condition known as “sarcopenic obesity” (Roubenoff R. Ann NY Acad Sci 904: 553–557, 2000). Research suggests that inflammatory cytokines produced by adipose tissue, especially visceral fat, accelerate muscle catabolism and thus contribute to the vicious cycle that initiates and sustains sarcopenic obesity. We tested the hypothesis that obesity and poor muscle strength, hallmarks of sarcopenic obesity, are associated with high circulating levels of proinflammatory cytokines in a random sample of the residents of two municipalities in the Chianti geographic area (Tuscany, Italy). The study sample consisted of 378 men and 493 women 65 yr and older with complete data on anthropometrics, handgrip strength, and inflammatory markers. Participants were cross-classified according to sex-specific tertiles of waist circumference and grip strength and according to a cut point for obesity of body mass index ≥30 kg/m2. After adjusting for age, sex, education, smoking history, physical activity, and history of comorbid diseases, components of sarcopenic obesity were associated with elevated levels of IL-6, C-reactive protein, IL-1 receptor antagonist, and soluble IL-6 receptor ( P < 0.05). Our findings suggest that global obesity and, to a greater extent, central obesity directly affect inflammation, which in turn negatively affects muscle strength, contributing to the development and progression of sarcopenic obesity. These results suggest that proinflammatory cytokines may be critical in both the development and progression of sarcopenic obesity.
Real-time lung microscopy
Authors: Kuebler Wolfgang M. , Parthasarathi Kaushik , Lindert Jens , Bhattacharya Jahar
Published: November 2006

Although proinflammatory cell signaling in the alveolo-capillary region predisposes to acute lung injury, key cell-signaling mechanisms remain inadequately understood. Alveolo-capillary inflammation is likely to involve coordinated signaling among cells of different phenotypes. For example, migration of inflammatory cells into the alveolus might entail coordinated signaling between adjoining alveolar epithelial and microvascular endothelial cells. The popular cultured cell experimental strategy fails to replicate this multicellular environment. Cultured lung cells, both alveolar and endothelial, undergo phenotypic transformations; hence they might inadequately reflect innate responses of native cells. Consequently, new approaches are required for the investigation of cell signaling in the native setting. Here we summarize new developments in classical intravital microscopy and discuss real-time fluorescence imaging as a novel technique for studying second-messenger mechanisms in the alveolo-capillary region.
Higher antibody, but not cell-mediated, responses to vaccination in high physically fit elderly
Authors: Keylock K. Todd , Lowder Thomas , Leifheit Kurt A. , Cook Marc , Mariani Rachel A. , Ross Kristine , Kim Kijin , Chapman-Novakofski Karen , McAuley Edward , Woods Jeffrey A.
Published: November 2006

The purpose of this study was to examine whether cardiovascular fitness, independent of confounding factors, was associated with immune responsiveness to clinically relevant challenges in older adults (60–76 yr). Thirteen sedentary, low-fit (LF; maximal O2uptake = 21.1 ± 1.1 ml·kg−1·min−1) and 13 physically active, high-fit (HF; maximal O2uptake = 46.8 ± 3.4 ml·kg−1·min−1) older adults participated in this study. Dietary intake was assessed, and a battery of psychosocial tests was administered. In vivo antibody and ex vivo proliferative and cytokine responses to influenza (Fluzone) and tetanus toxoid (TT) vaccination and delayed-type hypersensitivity skin tests were performed. HF elderly individuals displayed a higher antibody response to two of the three strains included in the Fluzone vaccine as measured by hemagluttination inhibition, but there was no difference between groups in influenza-specific ex vivo proliferation or IFN-γ or IL-10 production. HF elderly individuals exhibited a lower IgG1response and a tendency for a higher IgG2response to the TT vaccine. There were, however, no differences in TT-specific ex vivo proliferation or IFN-γ or IL-10 production. In contrast, HF subjects had higher proliferative responses to phytohemagluttinin. In addition, there were no differences in delayed-type hypersensitivity responses to fungal antigens between groups. These results suggest that, after accounting for confounding factors, HF elderly individuals have higher antibody responses to Fluzone vaccine and a Th2 skewing of the antibody response to TT. There was little evidence that HF mounted better cell-mediated immune responses to the Fluzone or TT vaccine measured in peripheral blood cells or to other recall antigens in vivo.
Lower extremity muscle size and strength and aerobic capacity decrease with caloric restriction but not with exercise-induced weight loss
Authors: Weiss Edward P. , Racette Susan B. , Villareal Dennis T. , Fontana Luigi , Steger-May Karen , Schechtman Kenneth B. , Klein Samuel , Ehsani Ali A. , Holloszy John O. ,   Washington University School of Medicine CALERIE Group
Published: November 2006

Caloric restriction (CR) results in fat loss; however, it may also result in loss of muscle and thereby reduce strength and aerobic capacity (V̇o2 max). These effects may not occur with exercise-induced weight loss (EX) because of the anabolic effects of exercise on heart and skeletal muscle. We tested the hypothesis that CR reduces muscle size and strength and V̇o2 max, whereas EX preserves or improves these parameters. Healthy 50- to 60-yr-old men and women (body mass index of 23.5–29.9 kg/m2) were studied before and after 12 mo of weight loss by CR ( n = 18) or EX ( n = 16). Lean mass was assessed by dual-energy X-ray absorptiometry, thigh muscle volume by MRI, isometric and isokinetic knee flexor strength by dynamometry, and treadmill V̇o2 max by indirect calorimetry. Both interventions caused significant decreases in body weight (CR: −10.7 ± 1.4%, EX: −9.5 ± 1.5%) and lean mass (CR: −3.5 ± 0.7%, EX: −2.2 ± 0.8%), with no significant differences between groups. Significant decreases in thigh muscle volume (−6.9 ± 0.8%) and composite knee flexion strength (−7.2 ± 3%) occurred in the CR group only. Absolute V̇o2 max decreased significantly in the CR group (−6.8 ± 2.3%), whereas the EX group had significant increases in both absolute (+15.5 ± 2.4%) and relative (+28.3 ± 3.0%) V̇o2 max. These data provide evidence that muscle mass and absolute physical work capacity decrease in response to 12 mo of CR but not in response to a similar weight loss induced by exercise. These findings suggest that, during EX, the body adapts to maintain or even enhance physical performance capacity.
Application of the Standard Photodynamic Treatment Protocol for Symptomatic Circumscribed Choroidal Hemangioma
Authors: Vicuna-kojchen Joaquin , Banin Eyal , Averbukh Edward , Barzel Israel , Shulman Marina , Hemo Itzhak , Pe’er Jacob , Chowers Itay
Published: November 2006

Purpose: To describe the results of photodynamic therapy (PDT) using a standard protocol, developed for treating choroidal neovascularization (CNV), for the treatment of circumscribed choroidal hemangioma (CCH). Methods: A prospective, uncontrolled, consecutive case series of patients with symptomatic CCH that were treated using the standard PDT protocol was evaluated periodically with ophthalmic exams and echography. Results: Nine CCH patients were included in the study. Mean tumor height decreased from 2.7 mm before treatment to 0.8 mm at the end of the follow-up period. Mean visual acuity improved from 6/15 to 6/12. Six patients required one PDT session, two patients two sessions, and one patient three sessions. Side effects included transient visual disturbances in two patients. One patient, who concomitantly presented with age-related macular degeneration, developed CNV. Conclusions: The standard PDT protocol is effective for the treatment of CCH. Complications are uncommon. Further studies should assess the optimal PDT protocol for the treatment of CCH.
Study of Patients with Ocular Hypertension with Scanning Laser Polarimetry and Short-Wavelength Automatic Perimetry
Authors: Georgopoulos Gerasimos T. , Halkiadakis Ioannis , Patsea Eleni , Papakonstantinou Dimitrios , Alexiou Michalis , Vergados Ioannis , Andreanos Dimitrios , Theodossiadis George , Moschos Michalis
Published: November 2006

Aims: To compare and correlate retinal nerve fiber layer (RNFL) measurements obtained by scanning laser polarimetry (SLP) with defects detected by short-wavelength automatic perimetry (SWAP) in eyes with ocular hypertension (OHT). Methods: SLP and SWAP were performed in 96 eyes of 48 consecutive patients with OHT. Results: Twenty-five eyes (26%) had SWAP visual field defects. Twenty-seven eyes (28.1%) had abnormal RNFL evaluation defined by the GDx neural network (‘number’ >29). Fourteen eyes of 10 patients (14.5%) had abnormal RNFL evaluation and SWAP visual field defects. RNFL thickness measurements were significantly reduced in eyes with abnormal SWAP. A weak but statistically significant correlation between the ‘number’ and pattern standard deviation (r = 0.3, p = 0.006) and the corrected pattern standard deviation (r = 0.3, p = 0.007) in SWAP was found. Areas of abnormal RNFL thickness corresponded to the localization of the SWAP visual field defects in corrected pattern deviation plots in 10 of the 14 eyes with defects in both tests. Conclusions: SWAP visual field defects frequently coexist and correspond with abnormalities of RNFL detected by SLP in eyes with OHT. In certain eyes, however, the two methods detect different glaucoma properties.
Medial Canthal Reconstruction by a Modified Glabellar Flap
Authors: Bertelmann Eckart , Rieck Peter , Guthoff Rudolf
Published: November 2006

Aims: To present a modified technique for the preparation of glabellar skin flaps to reconstruct medial canthal defects. Methods: Ten consecutively treated patients were included who had skin defects after resection of skin tumours like basal cell carcinomas in the medial canthal area of a medium vertical diameter of 2.5 cm. The defects were closed by preparation of a modified glabellar flap. The pedicle of the flap was guided through a skin tunnel prepared diagonally at the root of the nose. The pedicle was resected 4 weeks after the initial surgery. Results: In all 10 cases, the procedure was adequate for reconstruction of the defect. There were no flap necroses and the cosmetic results were favourable in all cases. The resection of the pedicle could be performed easily in an out-patient procedure 4 weeks after the operation. Conclusion: Glabellar flaps are established procedures to reconstruct medium to large defects of the medial canthus. Skin distortion in the area of the flap pedicle leading to a skin bulge and visible scars at the root of the nose and medial transposition of the eye brows can be reduced by a modification of the surgical technique preparing a skin tunnel for the flap pedicle. In our hands, the cosmetic results are better with the modified technique in comparison to the original procedure.
Flow Cytometrical Analysis of Adhesion Molecules, T-Lymphocyte Subpopulations and Inflammatory Markers in Pterygium
Authors: Tekelioglu Yavuz , Turk Adem , Avunduk Avni Murat , Yulug Esin
Published: November 2006

Background/Aim: Pterygium is a relatively frequent ocular surface disease with an unexplained etiopathogenesis. Our study was carried out with the aim to identify the presence of inflammatory cells and mediators such as T-lymphocyte subgroups (CD4 and CD8), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and human leukocyte antigen-DR (HLA-DR) in pterygium tissue. Methods: Pterygium tissue, obtained from 24 patients, and normal conjunctival tissue, from the nasal bulbar conjunctiva obtained from 14 patients operated for ocular perforations or vitrectomy, were separated into epithelial and stromal components under the microscope and suspended with phosphate-buffered saline solution to form a suspension. Cell suspensions were treated with specific antibodies for ICAM-1, VCAM-1, and HLA-DR and T-lymphocyte subgroups and evaluated with flow cytometry. The obtained data were compared statistically. Results: When compared to the control tissue samples, higher rates of ICAM-1-positive cells, VCAM-1-positive cells and HLA-DR-positive cells were recorded in pterygium tissue samples. CD4 and CD8 lymphocytes were also found to be at higher levels when compared to the control group. There was a statistically significant difference between the two groups. Conclusion: When compared with normal conjunctival tissue, pterygium tissue had increased levels of T-lymphocyte infiltration and inflammatory markers demonstrating the possible contribution of cellular immunity to the pathogenesis.
Morphological Changes of the Retrobulbar Optic Nerve and Its Meningeal Sheaths in Glaucoma
Authors: Pache Mona , Meyer Peter
Published: November 2006

This work focuses on the possible remodeling of the intraorbital portion of the optic nerve and its meningeal sheaths in glaucoma. The bulbar segments of the orbital optic nerve portion from 25 donors with glaucoma (M:F = 8:17; mean age ± SD 85 ± 11 years) and 25 controls (M:F = 14:11; mean age ± SD 81 ± 8 years) were formalin fixed, paraffin embedded and sectioned in series. Sections were stained with PAS, Masson trichrome and CD68, and examined for the following parameters: (1) diameter of the optic nerve; (2) thickness of the pia mater; (3) distance between dura mater and pia mater; (4) occurrence and amount of meningothelial cell nests in the subarachnoid space, and (5) presence and number of corpora arenacea. The mean diameter of the optic nerve was decreased in the glaucoma group when compared to the controls (2.9 ± 0.5 vs. 3.3 ± 0.5 mm; p < 0.01). The thickness of the pia mater was increased in the glaucoma group (0.1 ± 0.04 vs. 0.09 ± 0.03 mm, p < 0.05). Presence and number of corpora arenacea did not differ between the groups. Occurrence and amount of meningo- thelial cell nests in the subarachnoid space were however significantly increased in glaucoma (p < 0.02). Whether this observation is glaucoma specific deserves further investigation.
Corneal Ulcer Caused by a Wooden Foreign Body in the Upper Eyelid 6 Months after Minor Injury
Authors: Baumeister Martin , Kuhli-Hattenbach Claudia , Lüchtenberg Marc
Published: November 2006

Purpose: To describe a case of a wooden foreign body in the upper eyelid that remained asymptomatic for 6 months. Case Report: A 9-year-old boy was presented with moderate upper lid swelling. Medical history was positive for trauma with a wooden stick 6 months ago. At first, the condition resolved under local antibiotic treatment. Three weeks later, the inflammation recurred and a corneal ulcer developed. Examination under general anesthesia revealed a wooden foreign body which had remained in the upper eyelid since the first injury. Conclusion: Organic foreign bodies in the eyelid can remain asymptomatic for a long period of time and can play a role in periocular inflammation. In case of doubt, children and other less cooperative patients should be examined under general anesthesia.
Early-Onset Scleral and Corneal Ectasias following Low-Dose Mitomycin-C-Augmented Trabeculectomy in a Uveitic Glaucoma Patient
Authors: Pirouzian A. , O’Halloran H. , Scher C. , Jockin Y.
Published: November 2006

A case of early-onset sclerolimbal ectasia following low-dose topical mitomycin C application during uveitic glaucoma surgery is reported. Intraoperative and postoperative clinical courses were consistent with sclerolimbal ectasia. Adjunctive utilization of intraoperative low-dose 0.02% mitomycin C for the management of chronic uveitic glaucoma patients who are under concomitant systemic immunosuppressive regimen may enhance the risk of subacute postoperative sclerolimbal ectasia. Mitomycin C concentrations <0.02%, decreased scleral exposure time, and a strict informed consent policy are strongly recommended in this subset of uveitic patients.
An Improved Mouse Sca-1+ Cell-Based Bone Marrow Transplantation Model for Use in Gene- and Cell-Based Therapeutic Studies
Authors: Hall Susan L. , Lau K.-H. William , Chen Shin-Tai , Felt Joshua C. , Gridley Daila S. , Yee Jiing-Kuan , Baylink David J.
Published: November 2006

This study sought to develop a murine bone marrow transplantation strategy that would yield consistently high levels of long-term engraftment without significant morbidity and mortality. Hematopoietic stem cell (HSC)-enriched Sca-1+ cells were used for transplantation because of their propensity of homing to bone marrow. Green fluorescent protein (GFP)-expressing transgenic mice were used as donors. Murine Sca-1+ cells were enriched 13-fold from whole bone marrow with immunomagnetic column chromatography. Retroorbital injections yielded highly reproducible and higher levels of engraftment compared with tail vein injections. The combination of W41/W41 recipient mice and sublethal irradiation preconditioning produced long-term engraftment with minimal morbidity and mortality. A 24-hour delay between the sublethal irradiation and transplantation did not affect the efficiency and level of engraftment, but provided flexibility with respect to the timing of transplantation. Based on these findings, a mouse Sca-1+ cell-based strategy, involving the retroorbital injection of Sca-1+ cells into sublethally irradiated, myelosuppressed W41/W41 recipient mice within 24 h after irradiation, was developed. Transplantation of lentiviral vector-transduced wild-type Sca-1+ cells expressing GFP by this strategy led to consistently high levels of long-term engraftment. In summary, this murine Sca-1+ cell-based strategy could be used in studies of HSC-based gene or cell therapies.
The Multicenter Trial SAKK 37/95 of Cladribine, Cyclophosphamide and Prednisone in the Treatment of Chronic Lymphocytic Leukemias and Low-Grade Non-Hodgkin’s Lymphomas
Authors: Laurencet France , Ballabeni Pierluigi , Rufener Beatrice , Hess Urs , Cerny Thomas , Fey Martin , Luthi Jean-Marc , Plancherel Catherine , Zulian Gilbert B.
Published: November 2006

A multicenter trial was performed to confirm the therapeutic efficacy and the toxicity profile of the combination of cladribine, cyclophosphamide and prednisone in low-grade non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Twenty-three adults with previously treated (61%) or untreated (39%) NHL International Working Formulation A or Binet B and C CLL were administered cladribine 0.1 mg/kg/day as a subcutaneous bolus for 5 days, intravenous cyclophosphamide 500 mg/m2 on day 1, and oral prednisone 40 mg/m2 on days 1–5, every 4 weeks. Unexpected early hematological toxicities led to dose modifications for pretreated patients who received cladribine for 3 days only up to a maximum of five courses. Responses were observed in 75%, with 7 patients obtaining a complete clinical and hematological response. Median duration of complete response was 9 months. Median time to progression or relapse was 31 months. Myelosuppression and infections were dose limiting whereas posttreatment complications, including fatalities, resulted from infections. Median overall survival time from trial entry was 60 months. Activity of the combination of cladribine, cyclophosphamide and prednisone was confirmed. However, in the specific setting of a multicenter trial, unexpected fatal infectious episodes occurred in pretreated patients. Great caution is thus required in these susceptible patients and the routine use of corticosteroids should probably be abandoned.
Paraneoplastic Neurodegeneration in a Murine Host following Progressive Growth of a Spontaneous T-Cell Lymphoma: Role of Proinflammatory Internal Responses
Authors: Singh Mahendra Pal , Singh Gajendra , Singh Sukh Mahendra
Published: November 2006

Objective(s): In the present study, the mechanism of paraneoplastic neurodegeneration associated with progressive in vivo growth of a T-cell lymphoma of spontaneous origin has been investigated. Methods: Histologically, the brain was investigated by hematoxylin-eosin staining of brain sections. Western blotting was performed to detect the expression of cytokines and other proteins. Macrophage-derived interleukin-1 (IL-1) and tumor necrosis factor (TNF) was estimated by immunoassays. Induction of apoptosis in brain and tumor cells was determined by percent specific DNA fragmentation. Results: Tumor growth was associated with the development of multiple lesions in various regions of the brain along with alterations in the structure and alignment of Purkinje cells, and an increase in the water content in the brain. Brain extract and serum of tumor-bearing mice showed higher levels of proinflammatory cytokines. Induction of apoptosis is suggested to be the cause underlying the loss of cellularity of tumor-bearing hosts in the brain owing to an augmentation in the induction of the caspase-dependent pathway of programmed cell death. Further, the study presents investigations to show the role of nitric oxide and proinflammatory cytokines IL-1, TNF, interferon-γ and alkaline phosphatase in the manifestation of paraneoplastic neurodegeneration. Conclusions: Growth of a T-cell lymphoma is associated with the manifestation of neurodegeneration caused by soluble proinflammatory factors of tumor and/or host origin.
Effects of Thalidomide Treatment in Heart Failure Patients
Authors: Orea-Tejeda Arturo , Arrieta-Rodríguez Oscar , Castillo-Martínez Lilia , Rodríguez-Reyna Tatiana , Asensio-Lafuente Enrique , Granados-Arriola Julio , Dorantes-García Joel
Published: November 2006

Background: Several studies have reported a direct association between elevated plasma levels of inflammatory cytokines and worse functional class (New York Heart Association [NYHA]) and cardiac function, measured as left ventricular ejection fraction (LVEF). Thalidomide has recently shown to improve LVEF in chronic heart failure patients, accompanied by a marked decrease in plasma levels of tumor necrosis factor alpha (TNF-α). Methods: In a randomized prospective open label study of men and women with heart failure (HF) due to ischemic and non-ischemic cardiomyopathy who had systolic dysfunction (LVEF <40%) and NHYA classification, functional classes II and III were assigned to control (without thalidomide, 60 patients) or thalidomide group (20 patients). The initial dose of thalidomide was 100 mg once a day, and it was increased to 100 mg twice a day after a period of 10 days, if the prior dosage was well-tolerated. Demographic characteristics, etiology of HF, prior myocardial infarction, co-morbidities associated were registered and laboratory routine test, TNF-α serum levels, and echocardiogram were obtained at the beginning and after 6 months of follow-up. Results: Clinical status (NYHA) at the end of the follow-up period, improved moderately in both groups. TNF-α levels were initially of 5.88 ± 0.9 and 6.49 ± 1.82 vs. 6.32 ± 1.6 and 7.94 ± 3.8 pg/ml during follow-up, for thalidomide and control groups, respectively. There were non-significant differences in echocardiography variables. Conclusion: In conclusion, although there is a large amount of information supporting a direct relationship between TNF-α and worsening of symptoms and prognosis in patients with HF and recently, the beneficial effect on thalidomide treatment has been suggested, these preliminary observations should be confirmed in a larger prospective study, specially trying to clarify the action mechanisms.
Frequency of Hereditary Non-Polyposis Colorectal Cancer among Unselected Patients with Colorectal Cancer in Germany
Authors: Lamberti C. , Mangold E. , Pagenstecher C. , Jungck M. , Schwering D. , Bollmann M. , Vogel J. , Kindermann D. , Nikorowitsch R. , Friedrichs N. , Schneider B. , Houshdaran F. , Schmidt-Wolf I.G.H. , Friedl W. , Propping P. , Sauerbruch T. , Büttner R. , Mathiak M.
Published: November 2006

Introduction: Hereditary non-polyposis colorectal cancer (HNPCC) is a major form of familial colorectal cancer (CRC). It is diagnosed when either the Amsterdam criteria (AC) are fulfilled or mutations in one of the mismatch repair (MMR) genes have been identified. This project aims at estimating the proportion of HNPCC among unselected patients with CRC. Patients and Methods: During a period of 2 years, a total of 351 non-selected patients with CRC were registered prospectively. 92 patients met the Bethesda criteria (9 of them fulfilled the AC) and 259 did not. 348 tumours were examined for microsatellite instability (MSI) and expression of MMR proteins. Results: MSI-H and MSI-L were identified in 17 and 6%, respectively. Loss of MSH2 or MLH1 was found in 1.5 and 8.8%, respectively. Based on the results of tumour tissue analyses, 80 patients with MSI and/or loss of MSH2 or MLH1 expression were identified as candidates for germline mutation screening. DNA of 40/80 patients was available. These patients were screened for MSH2 and MLH1 mutations; 19/40 patients with MSI and normal MSH2 or MLH1 expression were screened for mutations in MSH6. Three patients had relevant MMR gene mutations and six variants of unknown functional relevance were detected. Conclusions: After adjusting for the cases not evaluable for germline mutations, 1.7% of the CRC patients had HNPCC proven by molecular genetics.
Tensile Strength and Host Response towards Silk and Type I Polypropylene Implants Used for Augmentation of Fascial Repair in a Rat Model
Authors: Spelzini Federico , Konstantinovic Maja L. , Guelinckx Isabelle , Verbist Godelieve , Verbeken Erik , De Ridder Dirk , Deprest Jan
Published: November 2006

Objective: We compared host response, architectural integration and tensile strength of two different macroporous silk constructs to a polypropylene type I implant in a rat model for augmentation of primary fascial defect repair. Materials and Methods: Animals were sacrificed on days 7, 14, 30 and 90 after implantation. The explants were evaluated macroscopically for infections, herniations and adhesions, mechanically for tensile strength, and histopathologically, to evaluate collagen deposition and inflammatory response. Results: The tensile strength of the explants showed a gradual increase for all materials. All implants uniformly shrank around one fifth by 90 days. In the silk implants, the inflammatory reaction showed a remarkable higher number of foreign body giant cells that characteristically spread from the periphery into implants. Collagen deposition was comparable for all the materials. In Silk a higher grade of neovascularisation was observed. Conclusion: Silk explants expressed high tensiometric strength, which was associated with a marked fibrotic process. The silk implants induced a strong foreign body reaction accompanied by microscopic signs of architectural degradation at 90 days. Polypropylene explants showed a more moderate foreign body reaction without architectural disturbance.
Torsion of a Nongravid Uterus with a Large Ovarian Cyst: Usefulness of Contrast MR Image
Authors: Matsumoto Hiroki , Ohta Tsuyoshi , Nakahara Kenji , Kojimahara Takanobu , Kurachi Hirohisa
Published: November 2006

Torsion of a nongravid uterus is extremely rare. Most cases of uterine torsion occur during pregnancy. Here we report a case of nongravid uterus torsion with a large adnexal mass. A 73-year-old woman presented at the emergency room with acute abdominal pain. A preoperative diagnosis of torsion of an ovarian cyst was made and laparotomy was performed. The left ovary was twisted 360° in a clockwise rotation, and the uterine corpus had also undergone a 360° rotation. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were carried out. Although a preoperative diagnosis of uterine torsion was not possible, it is noteworthy that in the contrast-enhanced magnetic resonance images the uterine cervix was intensely enhanced, while the uterine corpus was not. This is the first report to show the magnetic resonance imaging findings of a twisted uterus.
Microarray Analysis Reveals Overexpression of CD163 and HO-1 in Symptomatic Carotid Plaques
Authors: Ijäs Petra , Nuotio Krista , Saksi Jani , Soinne Lauri , Saimanen Eija , Karjalainen-Lindsberg Marja-Liisa , Salonen Oili , Sarna Seppo , Tuimala Jarno , Kovanen Petri T. , Kaste Markku , Lindsberg Perttu J.
Published: November 2006

Objective—

We studied by microarray analysis whether symptomatic and asymptomatic carotid plaques from the same patient differ in gene expression and whether the same changes are present in an independent sample set.

Methods and Results—

Carotid plaques from four patients with bilateral high-grade stenosis, one being symptomatic and the other asymptomatic, were analyzed on Affymetrix U95Av2 arrays. 33 genes showed >1.5-fold change between symptomatic and asymptomatic plaques in an intraindividual comparison with FDR ranging from 0.28 to 0.40. Three genes involved in iron-heme homeostasis, CD163, HO-1, and transferrin receptor, were further analyzed in 40 independent plaques. HO-1 (fold-change 1.93, 95%CI 1.04 to 3.94,
P
=0.040) and CD163 (1.58, 1.11 to 2.40,
P
=0.013) mRNAs were again induced, and also HO-1 protein was overexpressed in symptomatic plaques (4.38, 1.54 to 12.20,
P
=0.024). The expression of HO-1 and CD163 correlated with tissue iron content but iron itself was not associated with the symptom status.

Conclusions—

Symptomatic plaques show overexpression of CD163 and HO-1 both in intraindividual and interindividual comparison. Their expression correlates with iron deposits but asymptomatic and symptomatic plaques from isolated patients do not differ in macroscopic hemorrhages or iron deposits. We suggest that symptomatic plaques show a more pronounced induction of CD163 and HO-1 in response to plaque hemorrhages.
Gamma Glutamyl Transferase and Metabolic Syndrome, Cardiovascular Disease, and Mortality Risk
Authors: Lee Douglas S. , Evans Jane C. , Robins Sander J. , Wilson Peter W. , Albano Irene , Fox Caroline S. , Wang Thomas J. , Benjamin Emelia J. , D’Agostino Ralph B. , Vasan Ramachandran S.
Published: November 2006

Objective—To determine whether serum γ-glutamyl transferase (GGT) predicts cardiovascular disease (CVD) morbidity and mortality, accounting for temporal changes in known CVD risk factors and C-reactive protein (CRP).

Methods and Results—In 3451 Framingham Study participants (mean age 44 years, 52% women) we examined the relations of GGT with CVD risk factors, and prospectively determined the risk of new-onset metabolic syndrome, incident CVD, and death. GGT was positively associated with body mass index, blood pressure, LDL cholesterol, triglycerides, and blood glucose in cross-sectional analysis (P<0.005). On follow-up (mean 19 years), 968 participants developed metabolic syndrome, 535 developed incident CVD, and 362 died. The risk of metabolic syndrome increased with higher GGT (multivariable-adjusted hazard ratio [HR] per SD increment log-GGT, 1.26 [95%CI; 1.18 to 1.35]). Adjusting for established CVD risk factors (as time-dependent covariates updated quadriennially) and baseline CRP, a 1-SD increase in log-GGT conferred a 13% increase in CVD risk (P=0.007) and 26% increased risk of death (P<0.001). Individuals in the highest GGT quartile experienced a 67% increase in CVD incidence (multivariable-adjusted HR 1.67, 95%CI; 1.25 to 2.22).

Conclusion—An increase in serum GGT predicts onset of metabolic syndrome, incident CVD, and death suggesting that GGT is a marker of metabolic and cardiovascular risk.
Aging in the Atherosclerosis Milieu May Accelerate the Consumption of Bone Marrow Endothelial Progenitor Cells
Authors: Zhu Shoukang , Liu Xialin , Li Ying , Goldschmidt-Clermont Pascal J. , Dong Chunming
Published: November 2006

Objective—

We have demonstrated that bone marrow cells from young and wild-type (WT), but not old apoE
−/−
, mice are capable of preventing atherosclerosis. This study was performed to elucidate the numerical and functional changes underlying the efficacy difference between young and old bone marrow.

Methods and Results—

CD34
+
/VEGFR2
+
conventional endothelial progenitor cells and lin
−
/cKit
+
/Sca-1
+
hematopoietic stem cells did not differ numerically or functionally between young and old apoE
−/−
bone marrow. Fluorescence- activated cell sorter analysis, however, showed that a group of cells (simple little cells or SLCs), characteristically located in the lower left quadrant of forward scatter/side scatter flow cytometric plot, were markedly decreased in old WT and apoE
−/−
marrow, but abundantly present in young WT and apoE
−/−
bone marrow. The SLC fraction was mainly composed of lin
−
/cKit
−
/Sca-1
−
cells. In vitro differentiation assay demonstrated substantially more efficient endothelial differentiation of lin
−
/cKit
−
/Sca-1
−
SLCs than other bone marrow fractions at a single cell level and en masse. Furthermore, old lin
−
/cKit
−
/Sca-1
−
SLCs had a trend of decreased endothelial differentiation capability.

Conclusions—

Lin
−
/cKit
−
/Sca-1
−
SLCs may represent a previously unrecognized cell population, enriched for endothelial progenitors. The identification of these cells may help improve the efficacy of cell therapy.
The Vasohibin Family
Authors: Sato Yasufumi , Sonoda Hikaru
Published: November 2006

Biological phenomena are under the precise control by the genome. For the regulation of angiogenesis, proangiogenic genes such as VEGFs and angiopoietins are highly conserved, act specifically on endothelial cells, and play a fundamental role. In this sense, nature should prepare specific antiangiogenic genes as well. However, this counterpart of genomic regulation of angiogenesis remains to be established. We recently isolated a novel endothelium-derived angiogenesis inhibitor and named it vasohibin. Vasohibin is dominantly expressed in endothelial cells, induced by the stimulation with VEGF or FGF-2, and selectively affects on endothelial cells and inhibits angiogenesis. Although the mechanism of how vasohibin inhibits angiogenesis remains to be elucidated, our discovery of vasohibin as an endothelium-derived VEGF-inducible angiogenesis inhibitor should shed light on the genomic basis of the negative regulation of angiogenesis.
Establishment of a High Sensitivity Plasma Assay for Human Pentraxin3 as a Marker for Unstable Angina Pectoris
Authors: Inoue Kenji , Sugiyama Akira , Reid Patrick C. , Ito Yukio , Miyauchi Katsumi , Mukai Sei , Sagara Mina , Miyamoto Kyoko , Satoh Hirokazu , Kohno Isao , Kurata Takeshi , Ota Hiroshi , Mantovani Alberto , Hamakubo Takao , Daida Hiroyuki , Kodama Tatsuhiko
Published: November 2006

Objective—Plasma pentraxin 3 (PTX3) levels are increased in patients with acute myocardial infarction, yet its involvement in unstable angina pectoris (UAP) remains unclear. To critically evaluate the role of PTX3 in UAP, a sensitive and precise measurement of PTX3 concentration is needed.

Methods and Results—We established a high sensitive plasma ELISA assay system for the detection of PTX3 using monoclonal antibodies. The lower limit of detection of our ELISA was 0.1 ng/mL, sensitivity far greater than the current commercially available kit. Plasma samples were obtained from 162 consecutive patients treated for hypertension, hyperlipidemia, diabetes mellitus, or cardiovascular disease at a physician’s office. PTX3 was not associated with any known coronary risk factors. Additionally, we collected plasma samples from 252 consecutive subjects admitted to a university hospital for coronary artery assessment by coronary angiography. PTX3 was significantly increased in patients in whom coronary intervention was performed. We further analyzed the plasma level of PTX3 in 52 patients with effort angina (EAP) and 16 patients with UAP. Compared with the control group, PTX3 were significantly higher in the UAP group.

Conclusions—The levels of plasma PTX3 were increased in patients with arterial inflammation, especially UAP. This PTX3 detection system will be useful for the prediction of UAP.