bluuebunny/crossref_metadata_2025 huggingface dataset:
Membrane proteome analysis of the green‐sulfur bacterium Chlorobium tepidum
Authors: Aivaliotis Michalis , Corvey Carsten , Tsirogianni Irene , Karas Michael , Tsiotis Georgios
Published: October 2004

An extensive proteomic approach relies on the possibility to visualize and analyze various types of proteins, including membrane proteins, which are rarely detectable on two‐dimensional electrophoresis gels. In this study, different methods were employed for the enrichment of membrane proteins from Chlorobium tepidum prior to analysis with two‐dimensional electrophoresis (2‐DE). Isolated membranes were solubilized with Triton X‐100 and from the supernatant we identified 58 unique proteins. The use of ionic sodium dodecyl sulfate (SDS) for protein solubilization, combined with acetone precipitation, resulted in an improved 2‐DE pattern and the total number of the identified proteins was increased to 117. The use of acetone for protein precipitation improved the results by extracting compounds potentially deleterious to the resolution of 2‐DE. However, the additional proteins detected by the use of SDS are in the majority more difficult to solubilize than less hydrophobic proteins. Further our attempts for selective extraction of the outer membrane proteins using the acid glycine method allowed the identification of 37 proteins of which 14 were predicted to have a signal sequence indicating their localization in the periplasmic space or in the outer membrane.
Description of an ultrathin multiwire proportional chamber‐based detector and application to the characterization of theSpraguea lophii(Microspora) two‐dimensional genome fingerprint
Authors: Mansour Lamjed , Cheikali Chafik , Desaunais Pierre , Coulon Jean‐Pierre , Daubin Josette , Hassine Oum Kaltoum Ben , Vivarès Christian P. , Jeanjean Jack , Cornillot Emmanuel
Published: October 2004

Multiwire proportional chamber is a useful technology to build detectors that supersede the lack of interactivity of autoradiography in molecular biology experiments. Some drawbacks still limited the diffusion of existing instruments in biological laboratories. The major competitors are storage phosphor imaging systems. The simplified description of a radio‐chromato‐imager prototype (RCI) based on an original ultrathin multiwire proportional chamber is presented. It combines the advantage of the different existing technologies to present competitive properties in terms of efficiency, spatial resolution, robustness, manipulation easiness and production cost. Application of the RCI detector to molecular biology was performed by the analysis of karyotype and restriction display two‐dimensional pulsed‐field gel electrophoresis (KARD 2‐D PFGE) data which are used to describe small eukaryotic genome structures. The comparative analysis with autoradiography was performed with the PDQuest™ software onSpraguea lophii(Microspora) genome fingerprints. The spot detection procedure applied to the different images leads to a similar conclusion considering the genome structure ofS. lophiiwhich appeared to be composed of 15 chromosomes for 13 karyotypic bands (200–880 kbp).
Impact of pre‐treatment weight on weight trajectory in women treated for bulimia nervosa
Authors: Carter Frances A. , McIntosh Virginia V. W. , Joyce Peter R. , Gendall Kelly A. , Bulik Cynthia M.
Published: October 2004

Objective

To describe and evaluate changes in weight‐related measures over 5‐year follow‐up for weight status groups identified at pre‐treatment.

Methods

Participants were 134 non‐pregnant women who had participated in a randomized clinical trial for bulimia nervosa. Women were categorized according to their pre‐treatment body mass index (BMI; weight in kg/height in m2) into the following groups: low weight (BMI < 20), normal weight (BMI 20–25) and overweight (> 25). Participants were assessed across treatment and at yearly intervals (or more) over 5‐year follow‐up.

Results

Descriptive data and repeated measures analyses of variance show a trend for patients identified as being overweight at pre‐treatment to change (gain) more in weight and BMI over time than low weight or normal weight groups.

Conclusion

Weight status groups identified at pre‐treatment may have different patterns of weight change over time. Copyright © 2004 John Wiley & Sons, Ltd and Eating Disorders Association.
Personality and psychopathological traits of males with an eating disorder
Authors: Fernández‐Aranda F. , Aitken A. , Badía A. , Giménez L. , Solano R. , Collier D. , Treasure J. , Vallejo J.
Published: October 2004

Objectives

The aim of this study was to determine whether or not there are gender differences in personality, clinical features and associated traits in people with an eating disorder (ED)

Method

The participants consisted of 40 ED patients (20 males and 20 females) consecutively admitted to our hospital. The two groups were matched in terms of age, diagnosis and duration of illness. All patients fulfilled DSM‐IV‐R criteria for those pathologies.

Assessment

Assessment measures included the Eating Disorders Inventory‐2 (EDI‐2), the Symptom Check List (SCL‐90‐R) and the Temperament and Character Inventory‐R (TCI‐R), as well as a number of other clinical and psychopathological indices.

Results

In terms of personality traits, the males demonstrated less harm avoidance (p < 0.025) compared to females. Males showed significantly lower scores on drive for thinness (p < 0.007), impulse regulation (p < 0.043) and body dissatisfaction (p < 0.01). There were no gender differences on other symptomatological and psychopathological measures. The male group gave a history of premorbid overweight or obesity more frequently (45% vs 15%, p < 0.038)

Conclusions

The results of this study indicate that there were few gender differences in personality and psychological traits. However, higher premorbid obesity and overweight are more common antecedent factors in males. Copyright © 2004 John Wiley & Sons, Ltd and Eating Disorders Association.
Editors' notes
Authors: Rugg Deborah , Peersman Greet , Carael Michel
Published: October 2004

Editors' notes
Politics of monitoring and evaluation: Lessons from the AIDS epidemic
Authors: De Lay Paul , Manda Valerie
Published: October 2004

Monitoring and evaluation programs must strike a balance between generating meaningful tactical information for program managers while taking steps to ensure that public data use does not worsen discrimination and stigma toward people who are positive for the human immunodeficiency virus.
Developing and implementing monitoring and evaluation methods in the new era of expanded care and treatment of HIV/AIDS
Authors: Wolf R. Cameron , Bicego George , Marconi Katherine , Bessinger Ruth , van Praag Eric , Noriega‐Minichiello Shanti , Pappas Gregory , Fronczak Nancy , Peersman Greet , Fiorentino Renée K. , Rugg Deborah , Novak John
Published: October 2004

National program managers need data from different geographical areas within the country to plan for and monitor improvements in service coverage and capacity for care and treatment of patients with HIV/AIDS. They need to ensure equitable access to services by those in need.
Global standards for monitoring and evaluating national AIDS programs: Challenges, concerns, and needs of developing countries
Authors: Meda Nicolas
Published: October 2004

National monitoring and evaluation systems are failing to gather basic information. Too many data are being collected for various donors for their exclusive accountability purposes.
Cre recombinase specificity defined by the tau locus
Authors: Korets‐Smith Ella , Lindemann Lothar , Tucker Kerry Lee , Jiang Caoyang , Kabacs Nikolett , Belteki Gusztav , Haigh Jody , Gertsenstein Marina , Nagy Andras
Published: October 2004

We generated a transgenic mouse line (tau::Cre) by targeting the Cre to the tau locus (Mapt). Based on previous reports on the expression of Tau during development, we expected the Cre recombinase to be expressed in a neuron‐specific and pan‐neuronal manner. However, intercrosses between the tau::Cre and the Cre‐activatable reporter animals resulted in offspring with recombination either restricted to the nervous system or throughout the entire conceptus, indicating expression of Tau early in development. The percentage of neuron‐specific excision was dependent on the Cre reporter used representing different Cre target sites in the mouse genome. In spite of the observed variability, our data suggest that the tau::Cre mouse line can be used for pan‐neuronal recombination of floxed alleles when it is used with caution. genesis 40:131–138, 2004. © 2004 Wiley‐Liss, Inc.
CRBP‐III:lacZ expression pattern reveals a novel heterogeneity of vascular endothelial cells
Authors: Caprioli Arianna , Zhu Hongxin , Sato Thomas N.
Published: October 2004

Vascular endothelial cells are structurally and functionally heterogeneous. However, the molecular basis of this heterogeneity remains poorly defined. We used subtractive and differential screening to identify genes that exhibit heterogeneous expression patterns among vascular endothelial cells. One such gene is cellular retinol binding protein III (CRBP‐III/Rbp7). Analysis of the lacZ knockin line for this gene (CRBP‐III:lacZ) revealed a novel organ‐specific vascular endothelial expression pattern. LacZ was expressed in vascular endothelial cells in heart, skeletal muscle, adipose tissues, thymus, and salivary gland. However, it was not detected in other tissues such as brain, liver, and lung. Furthermore, the expression within each organ was primarily restricted to small capillary endothelial cells, but could not be detected in larger vessels. This organ‐specific vascular endothelial expression of CRPB:lacZ is relatively resistant to the changes of organ microenvironment. However, the level of expression can be modified by vitamin A deficiency. Therefore, our results provide novel molecular evidence for the heterogeneity of vascular endothelial cells. genesis 40:139–145, 2004. © 2004 Wiley‐Liss, Inc.
Isolation of mutations with dumpy‐like phenotypes and of collagen genes in the nematodePristionchus pacificus
Authors: Kenning Charlotte , Kipping Isabel , Sommer Ralf J.
Published: October 2004

The nematodePristionchus pacificuswas developed as a satellite system in evolutionary developmental biology and forward and reverse genetic approaches allow a detailed comparison of various developmental processes betweenP. pacificusandCaenorhabditis elegans. To facilitate map‐based cloning inP. pacificus, a genome map was generated including a genetic linkage map of ∼300 molecular markers and a physical map of 10,000 BAC clones. Here, we describe the isolation and characterization of more than 40 morphological mutations that can be used as genetic markers. These mutations fall into 12 Dumpy genes and one Roller gene that represent morphological markers for all sixP. pacificuschromosomes. Using an in silico approach, we identified ∼150 hits ofP. pacificuscollagen genes in the available EST, BAC‐end, and fosmid‐end sequences. However, 1:1 orthologs could only be identified for fewer than 20 collagen genes. genesis 40:176–183, 2004. © 2004 Wiley‐Liss, Inc.
Breast cancer risk associated with estrogen receptor expression in epithelial hyperplasia lacking atypia and adjacent lobular units
Authors: Gobbi Helenice , Dupont William D. , Parl Fritz F. , Schuyler Peggy A. , Plummer W. Dale , Olson Sandra J. , Page David L.
Published: October 2004

Estrogen is associated with many epidemiologic risk factors for invasive breast cancer. Cells that express estrogen receptors (ERs) in epithelial hyperplasia lacking atypia (EHLA) may influence breast cancer progression. We conducted a nested case‐control study of 268 women with biopsy‐confirmed EHLA to determine whether immunohistochemical expression of ERα in EHLA affects subsequent breast cancer risk. Study subjects could not have a prior or current history of breast cancer or atypical hyperplasia. Immunohistochemical stains in individual lesions and adjacent normal lobules were considered positive if ≥ 10% of epithelial cells stained for ERα. The risk of invasive breast cancer in EHLA patients with ERα‐positive normal lobules was twice that of other EHLA patients (95% CI = 1.0–3.8). This risk was not affected by the ERα status of EHLA lesions. ERα expression in adjacent normal lobules increases the moderate breast cancer risk previously associated with EHLA. © 2004 Wiley‐Liss, Inc.
Low doses of β‐carotene and lutein inhibit AOM‐induced rat colonic ACF formation but high doses augment ACF incidence
Authors: Raju Jayadev , Swamy Malisetty V. , Cooma Indranie , Patlolla Jagan M.R. , Pittman Brian , Reddy Bandaru S. , Steele Vernon E. , Rao Chinthalapally V.
Published: October 2004

Epidemiological studies suggest that carotenoids such as β‐carotene and lutein play an important role in reducing the risk for several cancers. However, in colon cancer there is ambiguity with regard to the role of these compounds in that both preventive effects and tumor promotion have been observed. In the present study we observed that male F344 rats were able to tolerate up to 2,500 ppm of β‐carotene as well as of lutein. We have then assessed the chemopreventive efficacy of β‐carotene and lutein at dose levels of ∼4 and 8% of the 2,500 ppm tolerated dose (TD) and also ∼40 and 80% of the TD on azoxymethane (AOM)‐induced colon carcinogenesis, using aberrant crypt foci (ACF) as a surrogate biomarker for colon cancer. Throughout the experiments, 5‐week‐old male F344 rats were fed the control diet (modified AIN‐76A) or experimental diets containing 100 or 200 ppm (∼4 or 8% of the 2,500 ppm TD), or 1,000 or 2,000 ppm (∼40 or 80% of the 2,500 ppm TD) of β‐carotene and lutein (n=10 rats/group). After 2 weeks on the experimental or control diets, all animals were injected with AOM (15 mg/kg body wt., once weekly for 2 weeks). At 14 weeks of age, all rats were killed, and their colons were evaluated for ACF. Administration of 100 or 200 ppm of β‐carotene inhibited AOM‐induced total colonic ACF formation by 24% (p<0.01) and 36% (p<0.001), respectively, whereas lutein at 200 ppm produced a 27% inhibition (p<0.01) yet had no significant effect at the 100 ppm dose level. Surprisingly, administration of 1,000 or 2,000 ppm of β‐carotene and lutein increased colonic ACF formation in a dose‐dependent manner, i.e., to 124% and 144% for the former and 110% and 159% for the latter. These results clearly suggest that further studies are warranted to determine whether the increase in ACF incidence by high doses of β‐carotene and lutein will also lead to an increase in tumor outcome. Taken together these data indicate that the chemopreventive activity of β‐carotene and lutein against colon carcinogenesis depends on the dose level. © 2004 Wiley‐Liss, Inc.
Investigation of human brain tumors for the presence of polyomavirus genome sequences by two independent laboratories
Authors: Rollison Dana E.M. , Utaipat Utaiwan , Ryschkewitsch Caroline , Hou Jean , Goldthwaite Patricia , Daniel Richard , Helzlsouer Kathy J. , Burger Peter C. , Shah Keerti V. , Major Eugene O.
Published: October 2004

JC virus (JCV), BK virus (BKV) and simian virus 40 (SV40) may be associated with human brain tumors. These polyomaviruses have been shown to induce brain tumors in experimentally infected animals. Several studies have found polyomavirus genomic sequences in human brain tumor tissues by using polymerase chain reaction (PCR), while others have not. Inconsistencies in previous findings may be due in part to small sample sizes and differences in underlying patient populations, laboratory techniques and quality control measures. To assess the role of polyomaviruses in human brain tumors and address inconsistencies of previous reports, we investigated the prevalence of viral sequences in a series of 225 brain tumor tissue specimens in 2 independent laboratories. PCR followed by Southern hybridization was performed at the National Institute of Neurological Disorders and Stroke (NINDS). Real‐time quantitative PCR was performed on the same tissues at Johns Hopkins University (JHU). Only those tumors with amplifiable DNA were tested further for polyomavirus sequences. Positive and negative control tissues were included, and all specimens were masked. Amplifiable DNA was detected in 225/225 (100%) tumors at NINDS, 9 (4%) of which contained polyomavirus sequences (3 JCV‐positive, 3 BKV‐positive and 3 SV40‐positive). The JHU laboratory amplified DNA from 165/225 (73%) tumors, of which 1 tumor tested positive (for SV40). No tumors tested positive in both laboratories. Results for masked quality control tissues were concordant between laboratories. Nucleotide sequences for JCV, BKV and SV40 are rarely present in a large series of adult and pediatric brain tumors. © 2004 Wiley‐Liss, Inc.
Tyrosine phosphorylation of PYK2 mediates heregulin‐induced glioma invasion: Novel heregulin/HER3‐stimulated signaling pathway in glioma
Authors: van der Horst Edward Htun , Weber Igor , Ullrich Axel
Published: October 2004

Receptor tyrosine kinases of the EGFR family transmit extracellular signals that control diverse cellular functions such as proliferation, differentiation and survival. Signaling function of a member of this family, HER3, is believed to be impaired due to deviations in its kinase consensus motifs. Here we address the functional role and signaling mechanisms of HER3. HER3 preferentially forms heterodimers with HER2 inducing the most potent mitogenic signal among EGFR family members. Our data show that in a glioma‐derived cell line the cytoplasmic tyrosine kinase PYK2 is constitutively associated with HER3 and that stimulation with Heregulin results in PYK2 tyrosine phosphorylation. HER3, but not HER2, mediates the phosphorylation of the C‐terminal region of PYK2 to promote a mitogenic response through activation of the MAPK pathway. A central role of PYK2 in signaling downstream of HER3 is substantiated by the demonstration that expression of a dominant‐negative PYK2‐KM construct abrogates the Heregulin‐induced MAPK activity and inhibits the invasive potential of glioma cells. These results suggest a novel Heregulin/HER3‐stimulated signaling pathway in glioblastoma‐derived cell lines that involves phosphorylation of PYK2 and mediates invasiveness of glioma cells. © 2004 Wiley‐Liss, Inc.
Invasiveness of breast cancer cells MDA‐MB‐231 through extracellular matrix is increased by the estradiol metabolite 4‐hydroxyestradiol
Authors: Paquette Benoit , Bisson Martine , Baptiste Catherine , Therriault Hélène , Lemay Rosalie , Cantin André M.
Published: October 2004

In malignant breast cancer, estrogen metabolism is altered, favoring the accumulation of hydroxyestradiols, which can generate free radicals. These reactive species can activate matrix metalloproteinases (MMPs), which in turn can hydrolyze the proteins of the extracellular matrix (ECM) that act as a barrier to tumor cell passage. The aim of this study was to determine whether reactive oxygen species generated by 4‐hydroxyestradiol (4‐OHE2) can activate MMP‐2 and then enhance the invasiveness of breast cancer cells MDA‐MB‐231 in vitro. Enzymatic assay and gel zymography demonstrated that 4‐OHE2 at a concentration as low as 10−8 M led to the conversion of proMMP‐2 to active MMP‐2. Activation of proMMP‐2 by 4‐OHE2 was inhibited by the Cu,Zn‐SOD supporting the involvement of the free radical superoxide anion (O). Using invasion chambers coated with matrigel (artificial ECM), 4‐OHE2 (10−8 M) enhanced the invasiveness of MDA‐MB‐231 breast cancer cells by 3‐fold. The addition of Cu,Zn‐SOD reduced the invasiveness of MDA‐MB‐231 cells by more than 2‐fold, supporting the involvement of O generated by 4‐OHE2. Addition of an MMP‐2 inhibitor completely inhibited the enhancement of invasiveness induced by 4‐OHE2, which demonstrates the importance of activating MMP‐2 by 4‐OHE2. On the other hand, estradiol, which does not have a catechol structure, did not generate free radicals, and it could not activate proMMP‐2 or enhance the invasiveness of beast cancer cells. Although these data need to be confirmed in an animal model, this study suggests that the accumulation of 4‐OHE2 in breast tumors could enhance the invasiveness of breast cancer cells. © 2004 Wiley‐Liss, Inc.
Dietary intervention in prostate cancer patients: PSA response in a randomized double‐blind placebo‐controlled study
Authors: Kranse Ries , Dagnelie Pieter C. , van Kemenade Monique C. , de Jong Frank H. , Blom Jan H.M. , Tijburg Lilian B.M. , Weststrate Jan A. , Schröder Fritz H.
Published: October 2004

The objective of this study was to show or to exclude an effect of dietary supplement on rising prostate‐specific antigen (PSA) levels. We have studied the effect of a dietary supplement (verum, administered for 6 weeks) containing plant estrogens, antioxidants, including carotenoids, selenium and other putative prostate cancer inhibiting substances in a randomized placebo‐controlled double‐blind crossover study in 37 hormonally untreated men with prostate cancer and increasing PSA levels. Outcome measures were changes in the rates of change of serum concentrations of total and free PSA and changes in male sex hormone levels. Male sex hormone levels were significantly lower during the verum phase (DHT: −0.11 nmol/L, p = 0.005; testosterone: −1 nmol/L, p = 0.02). Total PSA doubling time was unaffected. Free PSA, which increased during the placebo phase (average doubling time of 68 weeks), decreased during the verum period (average half‐life of 13 weeks; p = 0.02). In those men in whom the free androgen index decreased (21 out of 32), a significant decrease in the slopes of both total and free PSA was observed (p = 0.04). Overall total PSA doubling times did not increase significantly during verum. However, the study demonstrates that this dietary intervention reduces DHT and testosterone levels and increases free PSA doubling time (and total PSA doubling time in a relevant subgroup). If future studies confirm that these observations translate into a slowing of disease progression, a dietary intervention may become an attractive option for prostate cancer treatment and prevention. © 2004 Wiley‐Liss, Inc.
Bone marrow genesis after subcutaneous delivery of rat osteogenic cell‐seeded biodegradable scaffolds into nude mice
Authors: Gomi Kazuhiro , Kanazashi Mikimoto , Lickorish David , Arai Takashi , Davies John E.
Published: October 2004

This study describes the generation of an active hematopoietic marrow within the confines of a biodegradable, macroporous polyester scaffold, seeded with rat osteogenic cells, after subcutaneous implantation in nude mice. A macroporous, poly(DL‐lactide‐co‐glycolide) polymer scaffold, into which resorbable calcium phosphate particles were incorporated, was seeded with rat bone marrow‐derived cells. Scanning electron microscopy of the cell‐seeded scaffold demonstrated confluent cell colonization. Scaffolds seeded with cells were implanted under the dorsum of immunocompromised mice for 5 weeks. Histological analysis revealed bone formation along the scaffold pores creating bony cavities within which a host‐derived, hematopoietic marrow was observed which included hematopoietic precursors, megakaryocytes, fat cells, and numerous marrow sinusoids. In those areas where bone was not elaborated on the scaffold surface, no marrow genesis was observed and the scaffold interstices were filled with fibrous tissue. These results demonstrate the utility of this biodegradable scaffold in delivery of a phenotypically functional cell population for bone tissue and bone marrow engineering applications. Moreover, the recapitulation of hematopoietic marrow tissue within the engineered bony cavities also provides a new experimental environment with which to further investigate the interactions of hematopoietic and nonhematopoietic compartments of the marrow microenvironment. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 71A: 602–607, 2004
Plasmapheresis in the treatment of hyperthyroidism associated with agranulocytosis: A case report
Authors: Guvenc Birol , Unsal Cagatay , Gurkan Emel , Dincer Süleyman
Published: October 2004

Plasmapheresis, also known as therapeutic plasma exchange, is used in the treatment of several disorders. Temporary improvement after plasmapheresis in cases with thyrotoxicosis has been reported. A 55‐year‐old woman presented with agranulocytosis induced by propylthiouracil and clinical signs of heart failure. Three sessions of plasmapheresis were performed. We observed an improvement of thyroid hormone levels and clinical findings as well. Plasmapheresis can be an option when drug treatment of thyrotoxicosis fails. J. Clin. Apheresis 19:148–150, 2004. © 2004 Wiley‐Liss, Inc.
The generation of leukemic dendritic cells from acute myeloid leukemia cells is potentiated by the addition of CD40L at the terminal maturation stage
Authors: Lee Je‐Jung , Choi Bo‐Hwa , Nam Jong‐Hee , Park Myong‐Suk , Song Won‐Hyun , Yang Deok‐Hwan , Kim Yeo‐Kyeoung , Cho Sang‐Hee , Chung Ik‐Joo , Park Kyeong‐Soo , Lee II‐Kwon , Kim Hyeoung‐Joon
Published: October 2004

Leukemic dendritic cells (DCs) that are derived from acute myeloid leukemia (AML) cells display low‐level expression of several key molecules. We investigated the optimal combination of cytokines needed to generate potent leukemic DCs from AML cells in vitro. AML cells were cultured in the presence of the following combinations of cytokines: Group A, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) + interleukin‐4 (IL‐4) + tumor necrosis factor‐alpha (TNF‐α); Group B, GM‐CSF + IL‐4 + CD40L; and Group C, CD40L addition at the terminal maturation point of cells that were grown as for Group A. The AML cells showed clear upregulation of CD80, CD83, CD86, CD40, and HLA‐DR expression under all culture conditions, without significant differences between these groups. However, the addition of CD40L (as in Group C) showed a slight upregulation in the expression of CD83 and CD86 on leukemic DCs. The leukemic DCs in Groups A and B had higher allogeneic T‐cell stimulatory capacities than untreated AML cells, and the addition of CD40L (Group C) enhanced this effect. The function of the cytotoxicity‐stimulating autologous T cells was also augmented by the addition of CD40L (Group C). These results suggest that AML cells may be used to generate leukemic DCs using various cytokine combinations, and that the most potent, mature leukemic DCs are generated by the addition of CD40L to terminal‐stage AML cultures that are grown in the presence of conventional cytokine combinations. J. Clin. Apheresis 19:130–136, 2004. © 2004 Wiley‐Liss, Inc.
Differentiating thrombotic microangiopathies induced by severe hypertension from anemia and thrombocytopenia seen in thrombotic thrombocytopenia purpura
Authors: Egan J.A. , Bandarenko N. , Hay S.N. , Paradowski L. , Goldberg R. , Nickeleit V. , Brecher M.E.
Published: October 2004

Thrombotic microangiopathy (TMA) is a recognized complication of malignant hypertension (HTN). Such patients have blood pressures ≥200/140 mmHg but the condition is defined by the presence of papilledema and is frequently complicated by acute renal failure. Here we report two patients with severe HTN (systolic ≥180 mmHg or diastolic ≥120 mmHg), TMA, thrombocytopenia, renal failure, and, in one case, neurological changes (4 of 5 manifestations of the TTP pentad). A 50‐year‐old male with HTN presented with blurred vision, dizziness, headache, confusion, renal failure, and a TMA (PLT = 39 × 109/L and LD = 2,781 normal <600 U/L). On presentation, BP was 214/133 mmHg and an ophthalmic exam demonstrated no papilledema. With HTN control over 7 days, his platelet count rebounded (220 × 109/L), LD declined (1,730 U/L), and mental status improved. A 60‐year‐old female with diabetes, HTN, Lupus erythematosus, mild chronic anemia, and thrombocytopenia presented with abdominal pain, shortness of breath, renal failure, and a TMA (PLT = 83 × 109/L and LD = 2,929 U/L). Blood pressures were 180–210/89–111 mmHg and ophthalmic exam demonstrated no papilledema. With HTN control over 8 days, her platelet count rebounded (147 × 109/L), and LD declined (1,624 U/L). Although in both cases a diagnosis of TTP was considered because of overlap with the classic diagnostic pentad, neither received plasmapheresis. TTP is a diagnosis of exclusion, where there is no other likely diagnosis to explain the TMA. In cases of severe HTN (with or without papilledema), the diagnosis of TTP should be held in abeyance until the effect of HTN control can be assessed. J. Clin. Apheresis 19:125–129, 2004. © 2004 Wiley‐Liss, Inc.
Randomised phase 2 trial of SIR‐Spheres® plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer
Authors: Van Hazel Guy , Blackwell Anthony , Anderson James , Price David , Moroz Paul , Bower Geoff , Cardaci Giuseppe , Gray Bruce
Published: October 2004

Purpose

Selective internal radiation therapy (SIRT) with SIR‐Spheres® is a new technique for selectively targeting high doses of radiation to tumours within the liver. The primary objectives of this randomised trial were to compare the response rate, time to progressive disease (PD), and toxicity of a regimen of systemic fluorouracil/leucovorin chemotherapy versus the same chemotherapy plus a single administration of SIR‐Spheres in patients with advanced colorectal liver metastases. The trial was designed to presage a larger trial that would have survival as the primary outcome.

Patients and Methods

Twenty‐one patients with previously untreated advanced colorectal liver metastases, with or without extrahepatic metastases, were randomised into the study.

Results

Using RECIST criteria, the response rate for 11 patients receiving the combination treatment was significantly greater than for 10 patients receiving chemotherapy alone (First Integrated Response; 10 PR, 1 SD vs. 0 PR, 6 SD, 4 PD, P < 0.001 and Best Confirmed Response; 8 PR, 3 SD vs. 0 PR, 6 SD, 4 PD P < 0.001). The time to PD was greater for patients receiving the combination treatment (18.6 months vs. 3.6 months, P < 0.0005). Median survival was significantly longer for patients receiving the combination treatment (29.4 months vs. 12.8 months, P = 0.02). One patient in the combination arm died from chemotherapy induced neutropenic sepsis after the fourth chemotherapy cycle. There were more Grade 3 and 4 toxicity events in patients receiving the combination treatment. There was no difference in quality‐of‐life over a 3 month period between the two treatments when rated by patients (P = 0.96) or physicians (P = 0.98).

Conclusions

This small phase 2 randomised trial demonstrated that the addition of a single administration of SIR‐Spheres to a regimen of systemic fluorouracil/leucovorin chemotherapy significantly increased both treatment related response, time to PD, and survival with acceptable toxicity. The combination of SIR‐Spheres plus systemic chemotherapy is now the subject of ongoing trials to further define patient benefit. J. Surg. Oncol. 2004;88:78–85. © 2004 Wiley‐Liss, Inc.
Elevated expression of cyclooxygenase‐2 in breast cancer and ductal carcinoma in situ has no correlation with established prognostic markers
Authors: Singh Ranger Gurpreet , Jewell Andrew , Thomas Valerie , Mokbel Kefah
Published: October 2004

Background and Objectives

Elevated expression of cyclooxygenase‐2 (COX‐2) has been established to be a feature of breast cancer. There has been inconsistency in the literature regarding the precise significance of this—some studies have found no clinicopathological relevance at all, whilst others have concluded COX‐2 expression is an important biomarker in invasive disease and pre‐cancerous lesions, correlating with poor prognostic features. We studied COX‐2 expression in invasive ductal cancer (IDC) specimens and ductal carcinoma in situ (DCIS) in order to clarify these issues.

Method

Archival specimens of IDC and DCIS (n = 39) were stained with a polyclonal antibody to COX‐2. Results were correlated with recognised clinicopathological parameters.

Results

COX‐2 expression occurred in 36.7% of IDCs and 54.5% of DCIS lesions. There was no correlation between increased expression and any clinicopathological features. COX‐2 expression did not occur in adjacent non‐cancerous tissue (ANCT).

Conclusion

We have confirmed that COX‐2 expression does occur in invasive cancers, in DCIS, and is not associated with established prognostic markers. The presence of COX‐2 expression in DCIS and invasive cancers has positive implications for the future prevention and treatment of breast cancer with COX‐2 inhibitors. A large proportion of tumours are, however, COX‐2 negative and may be poor candidates for COX‐2 suppression. J. Surg. Oncol. 2004;88:100–103. © 2004 Wiley‐Liss, Inc.
Microbial reduction in periodontal pockets under exposition of a medium power diode laser: An experimental study in rats
Authors: Fontana Carla Raquel , Kurachi Cristina , Mendonça Cleber Renato , Bagnato Vanderlei Salvador
Published: October 2004

Background and Objective

This work evaluates the application of a 810 nm diode laser operating in the range of 400–1,200 mW for bacterial reduction at periodontal treatment. The aim of this study is to examine the immediate effect of the diode medium power laser in reducing the bacterial concentration at periodontal pockets induced in Wistar rats.

Study Design/Materials and Methods

Two bacterial collections were performed on each animal. Microbiological samples were collected before and immediately after laser irradiation. In each group of laser power, eight animals were used, totaling 40 animals.

Results

The initial and the final bacterial count revealed that laser irradiation induces considerable bacterial elimination, especially for Prevotella sp, Streptococcus beta‐hemolitico, Fusobacterium sp, Pseudomonas sp.

Conclusions

Our results indicate that this laser can constitute an alternative device to traditional infrared systems for bacterial reduction, with some advantage when economical and practical standpoints are considered. Lasers Surg. Med. 35:263–268, 2004. © 2004 Wiley‐Liss, Inc.
NIR laser tissue welding of in vitro porcine cornea and sclera tissue
Authors: Savage Howard E. , Halder Rabindra K. , Kartazayeu Uladzimir , Rosen Richard B. , Gayen Tapan , McCormick Steven A. , Patel Neil S. , Katz Alvin , Perry Henry D. , Paul Misu , Alfano R.R.
Published: October 2004

Background and Objective

The objective of this study was to test the hypothesis that an near infrared (NIR) laser system (1,455 nm) in combination with a motorized translational stage to control the position and speed of the laser beam and a shutter to control the laser exposure to the tissue being welded could be used to successfully weld ocular tissues.

Study Design/Materials and Methods

Seventy‐five porcine corneas and 23 porcine scleral tissues were welded in vitro in this study. The welded tissues were examined using histopathology and tensile strength analysis. Eight different welding conditions were analyzed for porcine cornea and one for sclera tissues. The tensile strength of the welded groups was compared to a sutured cornea control group.

Results

The NIR laser welding system provides strong, full thickness welds and does not require the use of extrinsic dyes, chromophores, or solders. Mean weld strengths of 0.15–0.45 kg/cm2 were obtained for the cornea and 1.01 kg/cm2 for sclera welds. The native H2O in the ocular tissue serves as an absorber of the 1,455 nm radiation and helps to induce the welds.

Conclusions

We conclude that an NIR laser system using an optimal laser radiation wavelength of 1,455 nm can effectively weld cornea and sclera tissue and that this laser tissue welding (LTW) methodology typically causes minimal disruption of tissue, and thus, avoids opacities and irregularities in the tissue which may result in decreased visual acuity. The optimization of a laser welding system that leads to a strong full thickness tissue bond without tissue destruction, an instant seal that promotes wound healing, and the absence of a continued presence of a foreign substance like a suture, is of considerable importance to the ophthalmology medical community. This need is especially apparent with respect to corneal transplantation and fixing the position of corneal flaps in Laser‐Assisted In Situ Keratomileusis (LASIK), a laser procedure used to permanently change the shape of the cornea. Lasers Surg. Med. 35:293–303, 2004. © 2004 Wiley‐Liss, Inc.
Time‐dependent hexaminolaevulinate induced protoporphyrin IX distribution after topical application in patients with cervical intraepithelial neoplasia: A fluorescence microscopy study
Authors: Andrejevic‐Blant Snezana , Major Attila , Lüdicke Franck , Ballini Jean‐Pierre , Wagnières Georges , van den Bergh Hubert , Pelte Marie‐Françoise
Published: October 2004

Background and Objectives

Compared to the conventional management of cervical intraepithelial neoplasia (CIN) the potential advantage of photodynamic therapy (PDT) for the treatment of cervical human papilloma virus (HPV)‐related disease encompasses a minimal invasive procedure with reduced risk of profuse bleeding as a consequence of conization, and possibly more favorable long‐term results avoiding cervical stenosis. At present little is known about the precise time‐dependent distribution and histological localization of hexaminolaevulinate (HAL) induced protoporphyrin IX (PPIX) fluorescence in healthy tissue and in CIN. The aim of this study was to use ex vivo fluorescence microscopy to determine whether PPIX is selectively induced by neoplastic cells of the cervical epithelium at various times after topical application.

Study Design/Materials and Methods

Cold cream containing 0.5% HAL was applied by means of cervical cap over various periods of time. We analyzed 52 healthy cervical mucosa and 84 CINs.

Results

At time delay 100 (±10) minutes, high epithelial fluorescence and a significant selectivity between epithelium and underlying lamina propria was found. By contrast, no significant difference between healthy and neoplastic tissues, or between low and high‐grade epithelial dysplasia (P ≥ 0.05), was observed at any time point.

Conclusions

Application of HAL 0.5% cream to the cervix induced selective fluorescence in epithelial cells. The optimal ratio with a homogeneous PPIX distribution was obtained after 100 ( ± 10) minutes cream application, which should be evaluated further for PDT. Lasers Surg. Med. 35:276–283, 2004. © 2004 Wiley‐Liss, Inc.
Intraluminal laser light source and external solder: In vivo evaluation of a new technique for microvascular anastomosis
Authors: Ott Beat , Constantinescu Mihai A. , Erni Dominique , Banic Andrej , Schaffner Thomas , Frenz Martin
Published: October 2004

Background and Objectives

Current laser‐assisted end‐to‐end anastomoses are performed by irradiating the vessel wall from outside after additional fixation with three to six sutures. These sutures are needed to provide adequate approximation of the vessel stumps. We present a new laser soldering technique that is based on an intraluminal laser light source centered in a balloon catheter, and external application of a solder. This technique was applied in vivo in order to test its feasibility under clinical conditions.

Study Design/Materials and Methods

Seven white pigs were treated with a total of fourteen end‐to‐end laser‐anastomoses of their saphenous arteries having outer diameters of 2 mm. The vessels were stented over an intraluminal balloon catheter, which was maximally dilated and which allowed for a precise approximation of the vascular stumps. An 808 nm diode laser was coupled into a specially designed optical fiber producing a 360° radiation ring inside the balloon catheter. An indocyanine green (ICG) doped liquid albumin solder was applied on the external surface of the vascular stumps. Laser soldering was achieved by irradiating with a 808 nm laser diode for 75 seconds. Tightness of the anastomoses was evaluated by clamping the artery distal to the anastomosis for 1 hour, and patency was tested over an observation period of 3 hours, during which the animals were heparinized. Thereafter, the anastomoses were harvested for histomorphological examination.

Results

All anastomoses remained patent over the entire observation period. Some leakage was observed in three anastomoses, which was explained by a deviation of the illumination fiber from the center of the balloon leading to an inhomogeneous irradiation of the vessel wall. Histology revealed perfect adaptation of the vascular stumps. A segment of denaturated vascular collagen was observed, that corresponded to the irradiated, solder‐covered zone.

Conclusion

Patent, maximally dilated and well adapted microvascular anastomoses could be obtained without the need of stay sutures. A well centered laser light source is indispensable for avoiding inhomogenous welding, thus causing leakage. Lasers Surg. Med. 35:312–316, 2004. © 2004 Wiley‐Liss, Inc.
In vivo optical coherence tomography for the diagnosis of oral malignancy
Authors: Wilder‐Smith Petra , Jung Woong‐Gyu , Brenner Matthew , Osann Kathryn , Beydoun Hamza , Messadi Diana , Chen Zhongping
Published: October 2004

Background and Objective

Oral cancer results in 10,000 U.S. deaths annually. Improved highly sensitive diagnostics allowing early detection of oral cancer would benefit patient survival and quality of life. Objective was to investigate in vivo non‐invasive optical coherence tomography (OCT) techniques for imaging and diagnosing neoplasia‐related epithelial, sub‐epithelial changes throughout carcinogenesis.

Study Design/Materials and Methods

In the standard hamster cheek pouch model for oral carcinogenesis (n = 36), in vivo OCT was used to image epithelial and sub‐epithelial change. OCT‐ and histopathology‐based diagnoses on a scale of 0 (healthy) to 6 (squamous cell carcinoma, SCC) were performed at all stages throughout carcinogenesis by two blinded investigators.

Results

Epithelial, sub‐epithelial structures were clearly discernible using OCT. OCT diagnosis agreed with the histopathological gold standard in 80% of readings.

Conclusion

In vivo OCT demonstrates excellent potential as a diagnostic tool in the oral cavity. Lasers Surg. Med. 35:269–275, 2004. © 2004 Wiley‐Liss, Inc.
Healing of perforating rat corneal incisions closed with photodynamic laser‐activated tissue glue
Authors: Khadem John , Martino Michael , Anatelli Florencia , Dana M. Reza , Hamblin Michael R.
Published: October 2004

Background and Objectives

Laser‐activated photodynamic biologic tissue glues may be useful for closing incisions in ophthalmology. We report on the use of two such preparations to close perforating corneal incisions in living rats.

Study Design/Materials and Methods

A previously described preparation containing a covalent albumin‐chlorin e6 (ce6) conjugate (bovine serum albumin (BSA)–ce6), and a novel mixture of albumin and Janus Green (BSA/JG), both activated with a 665‐nm diode laser were used to glue mouse skin ex vivo. The optimized glues were then used to seal incisions in rat corneas and results were compared to control incisions. Rats were sacrificed at day 1, 7, and 14 and eyes tested for leaking pressure and examined histopathologically.

Results

One day after treatment eyes closed with BSA–ce6 had a leaking pressure (in mmHg) of 357 compared to 193 for control incisions (P<0.01); closure with BSA/JG gave a leaking pressure of 430 (P<0.05 compared to BSA–ce6, and P<0.001 compared to control). Histological examination showed eyes sealed with BSA/JG have less inflammation present than untreated eyes at 7 days.

Conclusions

These data demonstrate that photodynamic laser activated tissue glues can be used to effectively seal corneal incisions in living animals without thermal damage or undue inflammation. Lasers Surg. Med. 35:304–311, 2004. © 2004 Wiley‐Liss, Inc.
Transformation of Biodegradable Polyesters into Cyclic Oligomers under Continuous Flow Using an Enzyme‐Packed Column
Authors: Osanai Yasushi , Toshima Kazunobu , Matsumura Shuichi
Published: October 2004

Summary: The enzymatic degradation of typical chemically synthesized biodegradable plastics, such as poly(butylene adipate) and poly(ε‐caprolactone), to a repolymerizable cyclic oligomer under continuous flow using an enzyme column was studied, directed towards green chemical recycling. It was confirmed that both polymers were quantitatively transformed into the corresponding cyclic oligomers by passage through the column packed with immobilized lipase from Candida antarctica (Novozym 435) at 40 °C using a toluene solution. Compared to the batch treatment in a flask, a short reaction time and a low reaction temperature occurred for complete transformations of the polyesters by continuous flow through the enzyme column. The degradation activity of the enzyme column was maintained for at least six months at 40 °C.

Conceptual scheme of the continuous degradation equipment using the enzyme column.

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Conceptual scheme of the continuous degradation equipment using the enzyme column.
Asymmetric ABC‐Triblock Copolymer Membranes Induce a Directed Insertion of Membrane Proteins
Authors: Stoenescu Roxana , Graff Alexandra , Meier Wolfgang
Published: October 2004

Summary: Asymmetric molecules and materials provide an important basis for the organization and function of biological systems. It is well known that, for example, the inner and outer leaflets of biological membranes are strictly asymmetric with respect to lipid composition and distribution. This plays a crucial role for many membrane‐related processes like carrier‐mediated transport or insertion and orientation of integral membrane proteins. Most artificial membrane systems are, however, symmetric with respect to their midplane and membrane proteins are incorporated with random orientation. Here we describe a new approach to induce a directed insertion of membrane proteins into asymmetric membranes formed by amphiphilic ABC triblock copolymers with two chemically different water‐soluble blocks A and C. In a comparative study we have reconstituted His‐tag labeled Aquaporin 0 in lipid, ABA block copolymer, and ABC block copolymer vesicles. Immunolabeling, colorimetric, and fluorescence studies clearly show that a preferential orientation of the protein is only observed in the asymmetric ABC triblock copolymer membranes.

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Spectrophotometric Determination of Deacetylation Degree of Chitinous Materials Dissolved in Phosphoric Acid
Authors: Hsiao Hsien‐Yi , Tsai Chih‐Cheng , Chen Suming , Hsieh Bo‐Chuan , Chen Richie L.C.
Published: October 2004

Summary: A simple spectrophotometric method is proposed for determining deacetylation degrees (DD) of chitinous materials using phosphoric acid as the UV‐transparent solvent system. Calibrating by the extinction coefficients (A210) of D‐glucosamine and N‐acetyl‐D‐glucosamine, DD values (24–88%) were computed numerically. The results correlated well (R2 = 0.9805, n = 50) with those obtained by solid‐state 13C NMR.

Comparison of the results obtained by the proposed UV method and solid‐state 13C NMR.

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Comparison of the results obtained by the proposed UV method and solid‐state 13C NMR.
Modeling of the Phase Separation Behavior of Polydisperse Semi‐Flexible Diblock Copolymers
Authors: John Andreas , Friedel Peter , Pospiech Doris , Jehnichen Dieter , Kunert Christoph
Published: October 2004

Summary: A modified random phase approximation method with a cumulant expansion for the semi‐flexible structure factor of diblock copolymers was exercised to describe the phase separation behavior of semi‐flexible and polydisperse diblock copolymers. Scattering curves and spinodal diagrams were calculated applying monomer specific input parameters. The influence of polydispersity was included applying basic concepts of mathematical statistics utilizing several probability density distributions in the case of the two single blocks. In contrast to semi‐flexibility, the main effect of polydispersity was found to shift the spinodal up, thus to enlarge the range of existence of the homogeneous phase.

Twofold Schultz‐Zimm distribution of diblock copolymers.

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Twofold Schultz‐Zimm distribution of diblock copolymers.