bluuebunny/crossref_metadata_2025 huggingface dataset:
Weekly Low-Dose Docetaxel in Advanced Hormone-Resistant Prostate Cancer Patients Previously Exposed to Chemotherapy
Authors: Petrioli Roberto , Pozzessere Daniele , Messinese Simona , Sabatino Marianna , Di Palma Teresa , Marsili Stefania , Correale Pierpaolo , Manganelli Antonio , Salvestrini Francesco , Francini Guido
Published: May 2003

Objective: The aim of this study was to evaluate the activity and tolerability of docetaxel in patients with hormone-resistant prostate cancer previously exposed to chemotherapy. Methods: We enrolled 27 patients with hormone-resistant prostatic cancer that had progressed during first-line chemotherapy. The primary end-point was palliative response defined as a 2-point reduction in the 6-point present pain intensity scale, and an improvement in Karnofsky performance status of one 10-point category. The treatment consisted of weekly docetaxel 25 mg/m² body surface area administered by means of a 1-hour intravenous infusion with corticosteroid premedication. Results: The primary criterion of palliative response was met in 13 patients (48%) after eight treatment cycles; its median duration was 6 months (range 1–8). Mean global quality of life improved in 8 and 10 patients after respectively four and eight treatment cycles. After a median follow-up of 8 months, 21 patients had died: the median survival was 9+ months (range 2–18). Weekly docetaxel was very well tolerated: grade 3 neutropenia occurred in 1 patient and grade 3 anemia in 2. Conclusions: Weekly low-dose docetaxel is an effective and well-tolerated treatment for patients with hormone-resistant prostate cancer previously exposed to chemotherapy.
A Systemic Hyperthermia Oncologic Working Group Trial
Authors: Westermann A.M. , Wiedemann G.J. , Jager E. , Jager D. , Katschinski D.M. , Knuth A. , Vörde sive Vörding P.Z. , van Dijk J.D.P. , Finet J. , Neumann A. , Longo W. , Bakhshandeh A. , Tiggelaar C.L. , Gillis W. , Bailey H. , Peters S.O. , Robins H.I.
Published: May 2003

Background: Based on earlier clinical and preclinical studies, we conducted a phase II trial in metastatic sarcoma patients of the combination of 41.8°C (×60 min) radiant heat (Aquatherm®) whole-body hyperthermia (WBH) with ‘ICE’ chemotherapy. The ICE regimen consists of ifosfamide (5 g/m2), carboplatin (300 mg/m2) and etoposide (100 mg/m2), concurrent with WBH, with etoposide also on days 2 and 3 post-WBH. Methods: Therapy was delivered every 4 weeks for a maximum of 4 cycles. All patients received filgrastim or lenograstim. Results: Of 108 patients enrolled as of September 2001, 95 are evaluable for response. Of the evaluable patients (mean ECOG performance status ∼1; mean age 42.3; 58% male) 33 had no prior therapy for metastatic disease, and 62 were pretreated (mean: 1.5 prior regimens). The overall response rate was 28.4% (4 complete remissions and 23 partial remissions) with stable disease (SD) in 31 patients. For no prior therapy, the response rate was 36%; in pretreated patients it was 24%. The median overall survival by Kaplan-Meier estimates was 393 days (95% CI 327, 496); the median time to treatment failure was 123 days (95% CI 77, 164). The major toxicity (287 cycles) was grade 3 or 4 neutropenia and thrombocytopenia seen in 79.7 and 60.6% of treatments respectively; there were 7 episodes of infection (grade 3/4) with 2 treatment-related deaths, bot involving disease progression and ureteral obstruction. Conclusion: These results are consistent with continued clinical investigation of this combined modality approach.
Endometrial Cancer and the IGF System: A Case-Control Study in Greece
Authors: Petridou Eleni , Koukoulomatis Panagiotis , Alexe Delia Marina , Voulgaris Zannis , Spanos Evagelos , Trichopoulos Dimitrios
Published: May 2003

Objectives: Insulin-like growth factor I (IGF-I) and other components of the IGF system have been implicated in the etiology of several human malignancies. We have undertaken a case-control study among Greek women to explore the relation of major components of the IGF system (IGF-I, IGF-II and IGF-binding protein 3, IGFBP-3) with endometrial cancer risk. Methods: During a 1-year period (1999), 84 incident cases of histologically confirmed endometrial cancer were compared with 84 control women admitted to the same clinical department for small gynecological operations, mainly pelvic prolapse. Data were modeled through multiple logistic regression. Results: Endometrial cancer was positively associated with IGF-II and inversely with IGF-I. Both associations were statistically significant and they appear symmetrical around the null value. IGFBP-3 is positively associated with endometrial cancer risk, but this association does not reach statistical significance. Conclusions: This study adds to the gradually developing consensus that components of the IGF system play a central role in human carcinogenesis. It is possible that IGF-II, rather than IGF-I, is closely linked to the etiology of endometrial cancer, the form of cancer most strongly associated with obesity.
Radiation Treatment for Aggressive Fibromatosis: Findings from Observed Patterns of Local Failure
Authors: Park Hee Chul , Pyo Hong Ryull , Shin Kyoo-Ho , Suh Chang Ok
Published: May 2003

Purpose: We retrospectively evaluated the outcome of patients treated with radiotherapy, with or without surgery, for aggressive fibromatosis. The patterns of local failure were analyzed to determine the optimum radiation dose and volume for irradiation. Patients and Methods: Twenty-four patients with histologically confirmed aggressive fibromatosis were treated with radiation therapy at the Yonsei Cancer Center between 1990 and 1998. The radiation dose per patient ranged from 39.6 to 59.4 Gy (mean: 49.4 Gy). The entire operative bed, with a generous margin, was included in the radiotherapy volume. Patients were considered as locally controlled if there was no evidence of the disease during their follow-up period, and if the tumors were stable for more than 2 years. The minimum duration of the follow-up period was 26 months, with a median of 69 months. Results: The actuarial 10-year recurrence-free and overall survival were 88.5 and 100%, respectively. Patients who had a recurrence were salvaged by combined surgery and re-irradiation. Recurrences developed only in patients who had a recurrent disease after surgery and were treated with an inadequate radiation volume. In 9 patients with a gross measurable disease, there were no in-field failures; these had been treated with a median of 50.4 Gy (range: 40–60 Gy) of radiation. Eight patients with a microscopic residual disease were also locally controlled with 41.4–59.4 Gy (median: 45 Gy) of radiation. No patient has developed either secondary malignancy or any serious radiation complications. Conclusion: Radiotherapy for aggressive fibromatosis can be an effective treatment option for maintaining a disease-free status. As fibromatosis, with either a microscopic, or a gross residual disease, can be controlled with a moderate dose of radiation, adjuvant postoperative radiotherapy following surgical excision is recommended with the least sufficient margin to preserve good function and cosmesis. The geographic relationship may require a more precise definition; in addition, regardless of the existence of neighborhood normal tissue barriers, a wide coverage of the radiation volume may be needed.
Heterogenous S-100B Protein Expression Patterns in Malignant Melanoma and Association with Serum Protein Levels
Authors: Bánfalvi T. , Udvarhelyi N. , Orosz Z. , Gergye M. , Gilde K. , Tímár J.
Published: May 2003

Objective: Serum S-100B is a reliable tumor marker of malignant melanoma, but efficient use is restricted to patients with metastatic disease. Therefore, the aim of our study was to assess serum S-100B levels at different stages of malignant melanoma and to compare these levels with the expression of the S-100B phenotype in primary tumors and lymph node metastases. Methods: Fifty-nine patients were included in this study; serum S-100B protein was measured using an immunoluminometric assay while the expression pattern in the primary tumor was determined by immunohistochemistry using an anti-S-100B monoclonal antibody. Results: Serum S-100B concentrations were significantly elevated in stage III (p = 0.01) patients, with normal levels in stage I–II. The most frequent S-100B protein expression pattern of the melanoma tissue was found to be diffuse staining observed in around half of the cases (52.5%) followed by heterogeneous (30.5%) and focal patterns (17%), being independent of the stage as well as the lymph node involvement. In stage I–II patients, the various staining patterns did not correlate with the serum concentration of the S-100B protein, while in stage III patients with heterogenous or diffuse S-100B staining patterns in tumor tissue, the serum marker concentration was significantly higher (p < 0.05) than in patients with focal staining. Furthermore, S-100B staining of the melanoma tissue also differed (low/negative, medium and strong staining), and serum marker concentrations corresponded to the pattern of the staining intensity. In stage I–II, only strong staining was associated with elevated serum S-100B concentrations while in stage III medium and strong staining was found to be associated with significantly higher serum marker concentrations compared to patients with tumors with low/negative staining (p < 0.05). Conclusions: In malignant melanoma characterized by focal and/or low S-100B staining in the tumor tissue determined by immunohistochemistry, S-100B monitoring in the serum may not suffice to detect disease progression.
Expression of Vascular Endothelial Growth Factor D Is Associated with Lymph Node Metastasis in Human Colorectal Carcinoma
Authors: Funaki Hiroshi , Nishimura Genichi , Harada Shin-ichi , Ninomiya Itasu , Terada Itsuro , Fushida Sachio , Tani Takashi , Fujimura Takashi , Kayahara Masato , Shimizu Koichi , Ohta Tetsuo , Miwa Koichi
Published: May 2003

Objective: Expression of vascular endothelial growth factor (VEGF)-D by tumors is associated with metastasis to lymph nodes in mice. However, there are few reports concerning the clinical significance of VEGF-D protein in human carcinoma. Methods: After confirming production of VEGF-D by eight colorectal carcinoma cell lines, we investigated relationships between the expression of VEGF-D protein, lymph node metastasis and postoperative survival in 83 colorectal carcinoma patients. mRNA levels in cell lines were evaluated using the real-time reverse transcriptase-polymerase chain reaction, and protein was detected by Western blotting in cell lines and by immunohistochemistry in resected tissues using an antibody recognizing the processed form of the molecule. Results: Immunohistochemistry showed VEGF-D-positive staining in 26 of the 83 carcinomas (31%). There was a significant relationship between the presence of VEGF-D protein and the incidence of lymph node metastasis (p < 0.01). Multivariate logistic regression analysis revealed that VEGF-D protein expression was an independent factor affecting lymph node metastasis (p < 0.01). Nonetheless, the presence or absence of VEGF-D protein had no significant impact on the survival of the patients (p = 0.15). Conclusion: These results suggest that the expression of VEGF-D protein could be useful in predicting the nodal status of colorectal carcinoma patients.
Reduced Expression of the TSP1 Gene and Its Association with Promoter Hypermethylation in Gastric Carcinoma
Authors: Oue Naohide , Matsumura Shunji , Nakayama Hirofumi , Kitadai Yasuhiko , Taniyama Kiyomi , Matsusaki Keisuke , Yasui Wataru
Published: May 2003

Thrombospondin-1 (TSP1) is a potent peptide shown in some tumor systems to be linked with angiogenesis. Epigenetic alteration of TSP1 has been reported in various primary tumors. However, the expression pattern of TSP1 has not been characterized in gastric carcinoma. We measured levels of TSP1 mRNA expression using quantitative RT-PCR in 30 gastric carcinomas and 10 non-neoplastic mucosae. In addition, we examined the correlation of the levels of TSP1 mRNA expression levels with promoter methylation status of TSP1 monitored by methylation-specific PCR as well as p53 mutation status detected by PCR-single-strand conformation polymorphism. Promoter hypermethylation of the TSP1 gene was found in 10 (33%) of 30 gastric carcinomas, and TSP1 mRNA expression levels were associated with promoter hypermethylation of TSP1 (p = 0.017; Mann-Whitney U test). p53 mutation was found in 5 (17%) of 30 gastric carcinomas, however, TSP1 mRNA expression was not associated with p53 mutation status (p = 0.858; Mann-Whitney U test). There was no correlation between TSP1 mRNA expression levels and T grade, N grade, tumor stage, or histological type. Our results suggest that transcriptional inactivation of TSP1 by aberrant DNA methylation of the promoter region may participate partly in stomach carcinogenesis through TSP1 down-regulation.
Apoptotic Index and bcl-2 Expression as Prognostic Factors in Colorectal Carcinoma
Authors: Bendardaf R. , Ristamäki R. , Kujari H. , Laine J. , Lamlum H. , Collan Y. , Pyrhönen S.
Published: May 2003

Objectives: To examine programmed cell death in 57 colorectal carcinomas (49 primary tumours and 8 metastases) and determine the prognostic significance of apoptosis in colorectal cancer. Methods: Apoptotic index (AI) was ascertained by counting apoptotic bodies, using terminal deoxynucleotidyl transferase mediated digoxigenin nick end labelling (Tunel assay) and the expression of bcl-2 was examined immunohistochemically. Statistical analysis was used to test the value of clinical variables, histopathological data, AI and bcl-2 expression in predicting the clinical outcome of these patients and the survival function was calculated using the Kaplan-Meier method. Results: AI was found to have a significant independent effect on survival (p = 0.0006), with lower values of AI conveying better survival. Conclusion: In summary, these findings reveal that AI is a useful prognostic factor in colorectal carcinoma.
Relationship and Differential Validity of Alexithymia and Depression: A Comparison of the Toronto Alexithymia and Self-Rating Depression Scales
Authors: Müller Jochen , Bühner Markus , Ellgring Heiner
Published: May 2003

Theoretically, the constructs of alexithymia and depression share many common characteristics. Empirically moderate correlations between measures of alexithymia and depression have been found, hence it has been argued that the Toronto Alexithymia Scale (TAS) may be, at least in some part, just another measure for depression. The purpose of this study was to evaluate the construct validity of alexithymia and to analyze the relationship between alexithymia and depression. Exploratory and confirmatory factor analyses were conducted on the combined items of the TAS-20 and the Self-Rating Depression Scale (SDS) in a psychosomatic and alcoholic inpatient sample (n = 199) and a sample of normal adults (controls, n = 174). The exploratory factor analysis in the patient sample yielded a 4-factor structure. Within each factor there was no overlap between the items of the TAS-20 and the SDS. Two factors were comprised of items of the TAS-20 and two factors consisted of items of the SDS. This 4-factor model also showed an acceptable fit for the data of the normal sample in a confirmatory factor analysis. Moderate correlations between the TAS- 20 and SDS total scores and some factors were found. Both instruments, the TAS-20 and the SDS, seem to measure distinct constructs and are not just different measures for the same underlying construct. This provides support for the differential validity of the alexithymia and depression constructs and is in accordance with previous findings.
Combining the Rorschach Test and the Temperament Character Inventory: A New Perspective on Personality Assessment
Authors: Fassino S. , Amianto F. , Levi M. , Rovera G.G.
Published: May 2003

Background: The numerous reports on research involving the clinical assessment of personality in axis I disorders highlight the importance of temperament features in the current approach to all mental disorders. However, the available instruments of personality assessment have many limits. Self-administered questionnaires depend on the patient’s insight, and projective instruments (i.e. the Rorschach test) often lack objectivity. This study compared the results of personality assessment with the Temperament and Character Inventory (TCI) and the Rorschach test to verify their validity. Patients and Methods: TCI and Rorschach tests were administered to a wide sample of patients (n = 180) in a short period. The most common Rorschach siglatures were correlated with the TCI raw scores using the Pearson correlation test. Results: All TCI temperament dimensions and facets displayed at least two correlations with Rorschach siglatures. The description of each dimension and facet of the TCI obtained with the interpretation of Rorschach siglatures was consistent with its original meaning. Conclusions: The TCI and Rorschach tests adequately validated each other. In the future, the administration and integration of these tests will overcome the biases of both. Further, the theoretical bases of the TCI could facilitate the study of psychological functions, whereas the psychodynamic bases of the Rorschach test provide an in-depth insight into temperament traits.
Musical Hallucinations in Schizophrenia
Authors: Baba Akira , Hamada Hidemichi , Kocha Hiroki
Published: May 2003

The musical hallucinations reported by 33 schizophrenics who fulfilled ICD-10 diagnostic criteria were assessed semiologically. The subjects were 24 men and 9 women. The duration of 48 episodes of musical hallucinations varied. They occurred at all times during the course of schizophrenia, and 9 of them (18.8%) occurred before the diagnosis was made. All of the episodes could be divided into three stages: 17 (35.4%) were first stage, close to obsession, 5 (10.4%) were second stage, close to Schneiderian first-rank symptoms, and 26 (54.2%) were third stage, which is the autochthonous experience. The sounds were in a subjective space in 38 episodes and in the majority of cases, their content was familiar. The second stage was associated with xenopathic experience (‘gemachtes Erlebnis’) and audition of thought, and words were added to melodies that normally had no lyrics. Musical hallucinations in schizophrenia are pseudohallucinations that originate in memory representations, and they may undergo a transition to true hallucinations. The authors think that the three stages are related to the severity of the disease.
Proliferation and Hepatic Differentiation of Adult-Derived Progenitor Cells
Authors: Wang Jian , Clark J. Brian , Rhee Gyu-Seek , Fair Jeff H. , Reid Lola M. , Gerber David A.
Published: May 2003

Hepatic progenitor cells, capable of maturing into hepatocytes and biliary cells, are hypothesized to be involved in all forms of liver regeneration and may prove clinically useful at reconstituting damaged livers. A murine hepatic progenitor cell population from young adult liver tissue has been isolated and characterized to establish a model for the development of liver cell therapies and for analysis of immune responses after transplantation. Hepatic progenitor cells were isolated from 3- to 6-week-old C57BL/6 mice using modifications of a two-stage liver perfusion technique followed by low speed centrifugation. Cellular analysis by phase contrast, fluorescent and confocal microscopy demonstrated that the hepatic progenitors (1) formed ex vivo colonies with a morphological appearance similar to committed hepatocytic progenitors isolated from embryonic mice and rats; (2) they are smaller than mature hepatocytes; (3) in culture they demonstrated peak expression of an oval cell marker at day 14, whereas albumin expression continued to increase beyond day 21 of culture, and (4) a subset of the progenitors phenotypically differentiated into mature hepatocytes or biliary cells. The unique antigenic profile of these hepatic progenitor cells and their ability to differentiate suggests that purification of the cells should allow for their potential use in transplantation.
Hyaluronan Is Differently Located in Arteries and Veins
Authors: Hellström Martin , Mattsson Cecilia , Hellström Sten , Engström-Laurent Anna
Published: May 2003

The matrix components of the vessel wall are of great importance for the function of the vessel system of which both endurance and elasticity are prerequisites. One component of the vessel wall is the glycosaminoglycan hyaluronan (HYA) with its unique physico-chemical properties, e.g. viscoelasticity and barrier function. The present study aimed to map and compare the normal localisation and distribution of hyaluronan in the arteries and veins of both adult and newborn rats, using a specific staining method utilizing a hyaluronan-binding protein. The hyaluronan stained clearly different in veins and arteries both in newborn and adult rats. In the veins, the tunica intima stained intensely whereas the corresponding area in the arteries only showed a weak and scattered staining pattern. In the adult rats, the matrix between the smooth muscle cells of the tunica media of the veins had a clearly positive staining pattern compared to the media in the arteries which showed only a few scattered areas of positive staining. In the newborn rats, the media of the arteries stained more intensely. In both newborn and adult rats, the adventitia stained intensely both in veins and arteries. Moreover, the HYA-staining pattern differed in veins in different regions of the body. Since HYA is known to be involved in many different biological processes, the results are of importance to understand physiological properties of the vessel tree and to explain the development of vascular diseases.
Adjuvant Chemotherapy after Radical Resection of Squamous Cell Carcinoma in the Thoracic Esophagus: Who Benefits?
Authors: Heroor Anil , Fujita Hiromasa , Sueyoshi Susumu , Tanaka Toshiaki , Toh Uhi , Mine Takashi , Sasahara Hiroko , Sudo Tomoya , Matono Satoru , Yamana Hideaki , Shirouzu Kazuo
Published: May 2003

Background: A definitive combined modality therapy superior to surgery alone has not yet been found for esophageal cancer. This retrospective study investigated the impact of postoperative adjuvant chemotherapy in patients who underwent curative (R0) esophagectomy with radical lymphadenectomy. Study Design: Two hundred and eleven patients with a squamous cell carcinoma in the thoracic esophagus who underwent transthoracic curative (R0) esophagectomy with radical lymphadenectomy, such as 3-field lymphadenectomy or total 2-field lymphadenectomy, between 1988 and 2000, were retrospectively reviewed. Ninety-four patients received postoperative chemotherapy – 2 courses of cisplatin (CDDP) plus fluorouracil (5-FU) or vindesine (VDS) – while the other 117 patients received surgery alone. The overall survival rate was compared between the two groups after being stratified by the numbers of the metastasis- positive lymph nodes. Results: Only in the subgroup of patients with 8 or more lymph nodes metastasis- positive, the surgery-with-postoperative-chemotherapy group had a significantly better survival than the surgery-alone group. No significant difference was found in survival between the two groups in any other stratified subgroup. Conclusions: Postoperative adjuvant chemotherapy following curative (R0) esophagectomy with radical lymphadenectomy such as 3-field lymphadenectomy or total 2-field lymphadenectomy provided a benefit only in patients having metastasis in a large number – 8 or more – lymph nodes.
Results of Endoscopic Septal Fenestration in the Treatment of Isolated Ventricular Hydrocephalus
Authors: Aldana Philipp R. , Kestle John R.W. , Brockmeyer Douglas L. , Walker Marion L.
Published: May 2003

A surgical series detailing the results and complications of neuroendoscopy for the treatment of isolated lateral ventricular hydrocephalus (ILVH) has yet to be presented. This retrospective case review of 32 patients examines our experience at the Primary Children’s Medical Center with endoscopic fenestration of the septum pellucidum (septostomy) for ILVH. The patients who underwent endoscopic septostomy between the years of 1993 and 2001 were identified from our database. Forty-three septostomies were performed, with a mean follow-up of 30.9 months. Fifty-three percent of initial septostomies remained patent. Nine patients had a least one more septostomy performed after failure of their initial septostomy. All but one was successful. Including repeat septostomies, 81% of the patients had relief of their ILVH on the last follow-up. No septostomy failures occurred later than 6 months postoperatively. A history of multiple previous shunt procedures was highly predictive of initial septostomy failure, increasing this risk 4.5 times. Complications involved significant intraventricular hemorrhage, wound breakdown, shunt infection and sterile meningitis in four cases. We conclude that endoscopic septostomy is a reasonable treatment option for ILVH, avoiding additional shunts. Outcome is negatively affected by multiple prior shunt procedures. Favorable results can be achieved with repeat septostomies in patients who have failed prior septostomy. Lasting results are expected for septostomies that remain patent after 6 months.
Brain Mapping for Hemispheric Tumors in Children
Authors: Gupta Nalin , Berger Mitchel S.
Published: May 2003

Hemispheric tumors are common in children. Pathologically, they range from indolent low grade astrocytic tumors to high grade malignant neoplasms. In general, the extent of resection correlates favorably with survival. Advances in technology are permitting surgical resection to be extended to near eloquent and eloquent regions of the brain. These techniques include advanced neuronavigation, brain mapping, and intra-operative MRI scanners. Incorporation of functional information in surgical planning should lead to safer surgical procedures with improvements in patient outcome.
Stereotactic Radiosurgery for CNS Nongerminomatous Germ Cell Tumors
Authors: Hasegawa Toshinori , Kondziolka Douglas , Hadjipanayis Constantinos G. , Flickinger John C. , Lunsford L. Dade
Published: May 2003

In this study, we evaluated the results in four patients with nongerminomatous germ cell tumors (NGGCT) of the pineal region. All underwent radiosurgery in conjunction with surgical resection, fractionated radiotherapy or chemotherapy. Four male patients with pineal region NGGCT were treated with radiosurgery. The mean age was 16.5 years. Three patients had histological confirmation by stereotactic biopsy or craniotomy prior to radiosurgery. One patient was diagnosed by serum and CSF tumor markers. The mean tumor volume was 10.5 cm3. Radiosurgery was performed with mean maximum and marginal doses of 28 and 14 Gy, respectively. At last follow-up, three patients were alive and one was dead. The mean follow-up after diagnosis and after radiosurgery was 34 and 25 months, respectively. At last follow-up, two tumors had regressed, one was unchanged and one had progressed. No patient had complications after radiosurgery. Radiosurgery can play an important adjuvant role for NGGCT patients who also undergo multimodal management. In the case of prepubertal patients, radiosurgery may play an important role by reducing the radiation dose to the surrounding normal brain.
A Late Result of an Early Operation for Unilateral Coronal Synostosis
Authors: Piatt Jr. Joseph H. , Iocono Joseph A.
Published: May 2003

An infant underwent strip craniectomy for unilateral coronal synostosis in 1967. This report presents the cosmetic, functional and psychosocial outcome at 34 years of age. Although aggressive, reconstructive treatment of the various forms of single-suture craniosynostosis is the current standard of care, neither the natural history of these conditions nor the long-term results of treatment have been documented systematically.
Effect of Low-Dose Aspirin on the International Normalized Ratio Variability in Patients with Mechanical Heart Valve Prostheses
Authors: Casais Patricia , Meschengieser Susana S. , Sanchez Luceros Analia G. , Bermejo Emilse I. , Lazzari Maria A.
Published: May 2003

An increased risk of bleeding is associated with a more intense oral anticoagulation, a greater international normalized ratio (INR) variability and the use of aspirin. We studied the INR variability of patients (n = 121) with modern heart valves who had been prospectively randomized to receive acenocoumarol at a targeted INR of 2.4–3.6 plus aspirin 100 mg/day or acenocoumarol alone at the same dosage, to evaluate whether aspirin influences variability and thus the risk of bleeding. Variability was similar in patients with no events regardless of the use of aspirin. A statistically significantly higher variability was observed in patients with bleeding events independently of the use of aspirin. Nevertheless, the concomitant use of aspirin in patients with a high variability should be monitored closely and thoroughly.
Effect of Phenprocoumon on Monitoring of Lepirudin, Argatroban, Melagatran and Unfractionated Heparin with the PiCT Method
Authors: Fenyvesi T. , Jörg I. , Harenberg J.
Published: May 2003

Prothrombinase-induced clotting time (PiCT) is a clotting-time test for heparins and direct thrombin inhibitors to reduce drawbacks of aPTT. Effects of the direct thrombin inhibitors lepirudin, argatroban, melagatran and of unfractionated heparin (UFH) were investigated in normal and oral anticoagulant plasma samples. Lepirudin showed potentiating interferences with phenprocoumon effects. Melagatran, argatroban and UFH delivered distinct linear additive effects in both plasma sample groups. PiCT ratio reduces differences between both groups with UFH, and argatroban inhibitor-receptor-binding mode plays a role in interaction patterns.
Impaired Flow-Mediated Vasodilation in vivo and Reduced Shear-Induced Platelet Reactivity in vitro in Response to Nitric Oxide in Prothrombotic, Stroke-Prone Spontaneously Hypertensive Rats
Authors: Taka Tomomi , Ohta Yoshio , Seki Junji , Giddings John C. , Yamamoto Junichiro
Published: May 2003

Previous investigations using an He-Ne laser-induced thrombosis method have shown that stroke-prone spontaneously hypertensive rats (SHRSP) have an enhanced thrombotic tendency in vivo compared to normotensive, Wistar Kyoto rats (WKY). In addition, studies in the presence of acetylcholine have suggested the presence of endothelial dysfunction in SHRSP. In contrast, shear-induced platelet reactivity in vitro appeared to be depressed in SHRSP. The aim of the present study was to investigate endothelial function in SHRSP using a new physiological in vivo model, and to determine the response of platelets to nitric oxide (NO) in non-anticoagulated blood using a shear-induced platelet function in vitro method (haemostatometry). Endothelial function was estimated by measuring flow-mediated vasodilation (FMV) of the femoral artery. Vessels were exposed and blood flow was arrested using a silicone-coated arterial clamp. Vasodilation was measured by computer-assisted image analysis 3 min after release of stasis. Arterial vasodilation was observed in the femoral artery of WKY, but not in SHRSP. Vasodilation was seen in both WKY and SHRSP; however, in response to the NO donor, 1-hydroxy-2-oxo-3-(3-aminopropyl)-3-isopropyl-1-triazene (NOC 5). In contrast, 100 µM NOC 5 did not affect platelet reactivity in SHRSP. The NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide, sodium salt (carboxy-PTIO) and the NO synthase inhibitor, NG-nitro-L-arginine methyl ester, hydrochloride (L-NAME), did not affect shear-induced platelet reactivity. NOC 5 at 10 µM (final concentration) inhibited shear-induced platelet reactivity in WKY. These results confirm the presence of endothelial dysfunction in SHRSP and indicate that platelets are non-responsive to NO in this hypertensive model. The data suggest that defective endothelial reactions or disturbed thrombogenic mechanisms outweigh the platelet hyporeactivity and contribute to the prothrombotic status in SHRSP.
Linkage and Association Studies of STAT6 Gene Polymorphisms and Allergic Diseases
Authors: Tamura Kazushi , Suzuki Michiko , Arakawa Hirokazu , Tokuyama Kenichi , Morikawa Akihiro
Published: May 2003

Background: Signal transducer and activator of transcription 6 (STAT6) is a key transcription factor involved in both interleukin-4 (IL-4) and IL-13-mediated biological responses, such as allergies. Recently, we reported that the polymorphism of the STAT6 gene exon 1 was associated with allergic diseases, while another group studied the G2964A variant of the STAT6 gene’s association with atopic asthma. We undertook an association study between these variants of the STAT6 gene and allergic diseases, including atopic dermatitis, bronchial asthma, and food-related anaphylaxis in a Japanese population. Methods: STAT6 gene polymorphisms were genotyped by polymerase chain reaction (PCR) fragment length polymorphism analysis, and PCR-SSCP analysis in 106 allergic and 66 control subjects. Results: The 2964A variant was in significant linkage disequilibrium with the dinucleotide repeat polymorphism, the 13-GT repeat allele of STAT6 exon 1 (p < 0.0000000003). There was no association between the STAT6 2964A variant and allergic subjects in a Japanese population (p = 0.2724). The genotype of 13/15-GT repeat allele heterozygosity was significantly associated with allergic subjects (p = 0.0006), as previously reported. In one major genotype of the STAT6 exon 1 (15 GT repeat homozygosity), wild-type 2964G allele homozygosity was significantly associated with allergic subjects (p = 0.0382). Conclusions: Our findings indicate that in combination the dinucleotide repeat polymorphism of the STAT6 exon 1 gene and the 2964A variant may be useful markers for predicting allergic diseases in a Japanese population.
Immunological and Clinical Changes in Allergic Asthmatics following Treatment with Omalizumab
Authors: Noga Oliver , Hanf Gerald , Kunkel Gert
Published: May 2003

IgE plays a key role in allergic asthma. We investigated whether omalizumab treatment of patients with moderate to severe allergic asthma leads to changes in inflammatory mediators and clinical symptoms. This sub-study was conducted on 35 patients with a positive skin prick test (SPT) requiring daily administration of beclomethasone dipropionate (500–1,000 µg), who participated in a multicentre, randomised, double-blind, placebo-controlled study. Omalizumab or placebo was administered at 0.016 mg/kg/IgE every 4 weeks. Patients recorded peak expiratory flow, asthma symptom score and β2-agonist use in daily diaries and spirometry was performed at each visit. β2-Agonist use and SPT wheal reaction decreased significantly (p < 0.05). Circulating levels of IL-5, IL-6, IL-8, IL-10, IL-13 and s-ICAM were measured before and after 16 weeks of treatment. IL-13 and s-ICAM were measured before and after 16 weeks of treatment. IL-13 decreased significantly (p < 0.01). IL-5 and IL-8 decreased in the omalizumab group compared to baseline. The other circulating mediators did not demonstrate any changes. Histamine release was significantly reduced (p < 0.01). Airway resistance (p < 0.05) and the provocative concentration inducing a 20% decrease in FEV1 (p < 0.05) were measured before, after 16 weeks, and 3 months after completion of treatment. Both parameters decreased significantly (p < 0.05). Peripheral eosinophil count decreased significantly compared to placebo (p < 0.01). These findings suggest that omalizumab has potential as a novel treatment for allergic asthma.
The Nonionic Radiocontrast Medium Iopromide Does Not Release Endothelin-1 or Activate Cardiac Mast Cells during Coronary Angiography
Authors: Simon Michael R. , Reher Randall L. , Long P. Michael , Yellayi Kalyani
Published: May 2003

Background: High osmolal ionic radiocontrast media (RCM) cause vascular release of endothelin-1 (ET-1) and activate mast cells. Iomeprol, a nonionic RCM, has recently been reported not to activate cardiac mast cells. This coronary angiography study was performed to extend those findings using another nonionic RCM, iopromide, and to further determine whether iopromide causes release of ET-1. Methods: Pulmonary artery plasma ET-1, histamine and serum tryptase were determined before and 30 min following angiography with iopromide in 11 subjects. ET-1, histamine and tryptase were measured using immunoassays. Results: The concentrations of ET-1 (1.36 ± 0.66 pg/ml), histamine (2.63 ± 1.15 nM), and β (<1 µg/l) as well as total tryptase (8.25 ± 4.63 µg/l) in the preangiography samples were within the normal range. Following angiography, the concentrations of ET-1 (0.95 ± 0.80 pg/ml), histamine (3.08 ± 1.06 nM), and β (<1 µg/l) and total tryptase (7.00 ± 5.56 µg/l) were not significantly different. None of the subjects demonstrated a postangiography increase in mediator concentration. Conclusions: This study demonstrates the lack of release of ET-1 by iopromide. The lack of cardiac mast cell activation by iopromide is consistent with the report that iomeprol also does not activate cardiac mast cells.
15-Deoxy-Δ12,14-Prostaglandin J2 Inhibits IFN-γ-Induced Galectin-9 Expression in Cultured Human Umbilical Vein Endothelial Cells
Authors: Imaizumi Tadaatsu , Kumagai Mika , Nishi Nozomu , Hirashima Mitsuomi , Hatakeyama Masaharu , Tamo Wakako , Yoshida Hidemi , Nakamura Takanori , Okumura Ken , Satoh Kei
Published: May 2003

Background: Galectin-9 is involved in chemotaxis and adhesion of eosinophils, and is induced in vascular endothelial cells by interferon-γ (IFN-γ). 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is a ligand for peroxisome proliferator-activated receptor-γ (PPAR-γ), and known to modulate the expression of various genes. Methods: We have studied the effect of 15d-PGJ2 on the IFN-γ-induced galectin-9 expression in human umbilical vein endothelial cells (HUVEC) in culture. Results: 15d-PGJ2 inhibited the IFN-γ-induced galectin-9 expression in a PPAR-γ-independent manner, and also inhibited the adhesion of EoL-1 cells to an HUVEC monolayer treated with IFN-γ. 15d-PGJ2 partially inhibited IFN-γ-induced phosphorylation of STAT-1 in HUVEC. Conclusions: 15d-PGJ2 may regulate inflammatory reactions through the inhibition of galectin-9 expression.
Transcriptional Control in Drosophila
Authors: Reinitz John , Hou Shuling , Sharp David H.
Published: May 2003

We present a new model of transcriptional control. A central goal of this model is to show how modular enhancers arise from groups of binding sites. The model has a three-layer organization. The first layer describes the binding of activators and repressors to the regulatory region of a gene and incorporates the effects of repression by competition and quenching. The second layer describes adapter molecules binding to DNA-bound activators, and incorporates the effect of direct repression. Finally, the activation of transcription is modeled by an Arrhenius mechanism in which activating adapters lower the activation energy barrier. We show that this model is testable against transcription data derived from early Drosophila embryos. We believe this model is sufficiently refined to give a realistic account of the physiological consequences of complex interactions of regulatory molecules. The present approach supplements and supports, in an essential way, the insights into multigenic regulation derived from work aimed at formulating logical design principles for regulatory networks.
Nanostructure Analysis Using Spatially Modulated Illumination Microscopy
Authors: Failla A.V. , Albrecht B. , Spöri U. , Schweitzer A. , Kroll A. , Hildenbrand G. , Bach M. , Cremer C.
Published: May 2003

For an improved understanding of cellular processes, it is highly desirable to develop light optical methods for the analysis of biological nanostructures and their dynamics in the interior of three-dimensionally (3D) conserved cells. Here, important structural parameters to be considered are the topology, i.e. the mutual positions and distances, as well as the sizes of the constituting subunits. This has become possible by the development of a novel method of far-field light fluorescence microscopy, spatially modulated illumination (SMI) microscopy. Using this approach, axial distances between fluorescence-labeled targets can be measured with an accuracy close to 1 nm; their sizes can be determined down to a few tens of nanometers. This approach can be extended to the determination of 3D positions and mutual 3D distances and sizes of any number of small objects/subunits that can be discriminated due to their spectral signatures. Consequently, the new approach allows an ‘in situ nanostructure elucidation, until now regarded to be beyond the possibilities of far-field light microscopy. Application examples discussed are: colocalization/nanosizing and topological analysis of large protein-protein complexes, of nucleic acid-protein complexes (such as transcription factories), or of the highly complex DNA-protein nanostructures of which active/ inactive gene regions in the eukaryotic cell nucleus are constituted.
Role of IgE in Th2 Cell-Mediated Allergic Airway Inflammation
Authors: Maezawa Yuko , Nakajima Hiroshi , Kumano Kotaro , Kubo Shuichi , Karasuyama Hajime , Iwamoto Itsuo
Published: May 2003

Recent studies with gene knockout mice have demonstrated that T helper 2 (Th2) cell-derived cytokines, including IL-4, IL-5, and IL-13, play important roles in causing allergic airway inflammation. In addition to Th2 cytokines, IgE-dependent activation of mast cells has been suggested to play a role in allergic airway inflammation. In this review, we will discuss the role of IgE in Th2 cell-mediated allergic airway inflammation. We used IgE transgenic mice, which enabled us to investigate the role of IgE without the influence of activated T cells and other immunoglobulins. Whereas IgE cross-linking by antigens did not induce eosinophil recruitment into the airways or airway hyperreactivity, IgE cross-linking induced CD4+ T cell recruitment into the airways. In addition, when antigen-specific Th2 cells were transferred to IgE transgenic mice, IgE cross-linking significantly enhanced antigen-induced eosinophil recruitment into the airways. These findings suggest that IgE-dependent mast cell activation plays an important role in allergic airway inflammation by recruiting Th2 cells into the site of allergic inflammation.
Distinct Isoforms of Protein Kinase C Are Involved in Human Eosinophil Functions Induced by Platelet-Activating Factor
Authors: Takizawa Takumi , Kato Masahiko , Suzuki Masato , Tachibana Atsushi , Motegi Youichi , Fujiu Toru , Kimura Hirokazu , Arakawa Hirokazu , Mochizuki Hiroyuki , Tokuyama Kenichi , Morikawa Akihiro
Published: May 2003

Background: Platelet-activating factor (PAF) is a potent stimulator of eosinophils. Recently, treatment with a protein kinase C (PKC) inhibitor which generally inhibits PKC isoforms has been shown to modulate several eosinophil functions in distinct manners, in that PKC inhibition enhanced CD11b expression and cellular adhesion, but inhibited superoxide generation and degranulation in PAF-stimulated human eosinophils. These results suggested that distinct PKC isoforms were likely to be involved in each eosinophil function induced by PAF. We have therefore investigated whether or not the PKC isoforms involved in PAF-induced CD11b expression and superoxide generation were different. Methods: Human eosinophils prepared from healthy volunteers were treated with PKC inhibitors, bis-indolylmaleimide I (BisI; a general PKC inhibitor), myristoylated PKC inhibitor peptide (myr-ψPKC; a PKCα, β and δ inhibitor) and rottlerin (a PKCδ inhibitor), followed by stimulation with PAF. CD11b expression was determined using flow cytometry and superoxide generation was evaluated using a cytochrome c reduction assay. Results: BisI treatment led to enhancement of PAF-induced CD11b expression, while myr-ψPKC and rottlerin did not. In contrast, PAF-induced superoxide generation was inhibited by treatment with BisI, myr-ψPKC and rottlerin. Conclusions: PKCα, β and δ are not involved in PAF-induced CD11b expression, but PKCδ is involved in the PAF-induced activation of superoxide anion generation.
Eosinophil Degranulation during Pregnancy and after Delivery by Cesarean Section
Authors: Matsumoto Kenji , Ogasawara Takahisa , Kato Atsushi , Homma Toshiki , Iida Makoto , Akasawa Akira , Wakiguchi Hiroshi , Saito Hirohisa
Published: May 2003

Background: The physiological roles of eosinophils that accumulate in the uterus during pregnancy and of uterus-dwelling mast cells remain unknown. In the present study, we investigated the degranulation of eosinophils and mast cells within the normal course of pregnancy and after delivery by measuring the urinary concentrations of eosinophil-derived neurotoxin (EDN) and N-methylhistamine. Methods: Spot urine samples from 65 pregnant women and 15 nonpregnant, age-matched women were examined. Urinary EDN and N-methylhistamine concentrations were measured by radioimmunoassay and standardized with urinary creatinine concentration. Results: A significant increase in the urinary EDN concentration was observed until the second trimester in the normal pregnancies. The elevated urinary EDN levels decreased after the onset of labor in the third trimester and normalized within 1 month after normal vaginal delivery. In women who underwent a cesarean section, the urinary EDN concentration was significantly higher for up to 1 month after delivery, compared to that in women who underwent a vaginal delivery. In contrast, the urinary N-methylhistamine concentration did not change until the second trimester and was significantly decreased during the third trimester. No significant correlation between the peripheral blood eosinophil count and the urinary EDN concentration was observed in these subjects. Conclusions: Eosinophils appear to play a role in the progression of pregnancy and recovery after a cesarean section through the degranulation of eosinophils. In addition, mast cell degranulation does not appear to be related to the contraction of uterine smooth muscle during labor.
Decreased Lymphocyte 3H-Paroxetine Binding in Obsessive-Compulsive Disorder
Authors: Marazziti Donatella , Baroni Stefano , Masala Irene , Giannaccini Gino , Mungai Francesco , Di Nasso Elena , Cassano Giovanni B.
Published: May 2003

The pathophysiology of obsessive-compulsive disorder (OCD) is mainly focused on the serotonin (5-HT) system and transporter. The presence of this structure in blood lymphocytes prompted us to investigate it, by means of the specific binding of 3H-paroxetine (3H-PAR), in a group of drug-free OCD patients as compared with healthy control subjects matched for sex and age. Lymphocyte membranes and 3H-PAR binding were carried out according to standard protocols. The results showed that the patients had a statistically significant lower density of 3H-PAR-binding sites than the control subjects. On one hand, this finding confirms previous data of an abnormal platelet 5-HT transporter in OCD, on the other it provides the possibility to explore the regulation of this structure in this and other disorders, since lymphocytes are nucleate cells.