bluuebunny/crossref_metadata_2025 huggingface dataset:
RSR13 Plus Cranial Radiation Therapy in Patients With Brain Metastases: Comparison With the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases Database
Authors: Shaw Edward , Scott Charles , Suh John , Kadish Sidney , Stea Baldassarre , Hackman John , Pearlman Andrew , Murray Kevin , Gaspar Laurie , Mehta Minesh , Curran Walter , Gerber Michael
Published: June 2003

Purpose: This phase II, open-label, multicenter study assessed the efficacy and safety of the potential radiation enhancer RSR13 plus cranial radiation therapy (RT) in patients with brain metastases. The primary end point was patient survival in comparison with the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases Database (RTOG RPA BMD).

Patients and Methods: Eligibility criteria were age ≥ 18 years, Karnofsky performance score ≥ 70, and brain metastases with solid tumor histology. Patients received cranial RT, 30 Gy in 10 fractions of 3 Gy each, preceded by RSR13, 50 to 100 mg/kg intravenously over 30 minutes. Univariate and multivariate comparisons of survival and cause of death were made between class II study patients and RTOG BMD patients.

Results: Fifty-seven RPA class II patients were enrolled. With a minimum follow-up of 24 months, the median survival time and 1- and 2-year survival rates were 6.4 months, 23%, and 11% for the RSR13-treated patients compared with 4.1 months, 15%, and 3% for the RTOG BMD patients (P = .0174). In an exact-matched case analysis (n = 38), median survival time for RSR13 patients was 7.3 months versus 3.4 months for the RTOG BMD patients (P = .006). There was a 54% reduction in the risk of death for RSR13 patients (P = .0267). RSR13-related adverse events of greater than or equal to grade 3 toxicity that occurred in more than one patient included hypoxia, headache, anemia, fatigue, hypertension, and intracranial hypertension.

Conclusion: RSR13 plus cranial RT resulted in a significant improvement in survival, as well as a reduction in death due to brain metastases, compared with class II patients in the RTOG BMD.
Single Nucleotide Polymorphism of the Human Kallikrein-2 Gene Highly Correlates With Serum Human Kallikrein-2 Levels and in Combination Enhances Prostate Cancer Detection
Authors: Nam Robert K. , Zhang William W. , Trachtenberg John , Diamandis Eleftherios , Toi Ants , Emami Marjan , Ho Minnie , Sweet Joan , Evans Andrew , Jewett Michael A.S. , Narod Steven A.
Published: June 2003

Purpose: We examined the relationship between a mutant (T) for wild-type (C) allele substitution of the human kallikrein-2 gene (KLK2), circulating human kallikrein-2 (hK2) levels and prostate cancer risk.

Patients and Methods: We studied 1,287 consecutive men who underwent prostate biopsies because of an abnormal prostate-specific antigen level. Serum and DNA were obtained before biopsy. Cases were patients with cancer, and controls were patients with no cancer. The mutant and wild-type alleles of the KLK2 gene were designated as the T and C alleles, respectively.

Results: Of the 1,287 men, 616 had cancer, and 671 had no cancer. The overall distribution of the CC, CT, and TT KLK2 genotypes was 55.1%, 38.2%, and 6.8%, respectively. The median hK2 levels for men with the CC, CT, and TT genotypes were 0.24, 0.18, and 0.062 ng/mL and correlated with the genotypes, respectively (P = .0001). The adjusted odds ratios for prostate cancer for patients with the TT and CT genotypes compared with patients with the CC genotype, were 2.13 (95% confidence interval [CI], 1.3 to 3.5; P = .004) and 1.51 (95% CI, 1.2 to 2.0; P = .002), respectively. The adjusted odds ratio for prostate cancer for patients in the fourth quartile of hK2 compared with the first quartile was 4.33 (95% CI, 2.9 to 6.4; P = .0001). When combined, the adjusted odds ratio for having prostate cancer was 13.92 (95% CI, 6.6 to 29.2; P = .0001) for patients with high hK2 levels and at least one T allele.

Conclusion: The C/T polymorphism of the KLK2 gene and circulating levels of hK2 are correlated and, in combination, are highly predictive for prostate cancer.
High-Dose Therapy and Autologous Stem-Cell Transplantation Versus Conventional Therapy for Patients With Advanced Hodgkin’s Lymphoma Responding to Front-Line Therapy
Authors: Federico Massimo , Bellei Monica , Brice Pauline , Brugiatelli Maura , Nagler Arnon , Gisselbrecht Christian , Moretti Luciano , Colombat Philippe , Luminari Stefano , Fabbiano Francesco , Di Renzo Nicola , Goldstone Anthony , Carella Angelo Michele
Published: June 2003

Purpose: To determine whether high-dose therapy (HDT) with autologous stem-cell transplantation (ASCT) should be included in the initial consolidative treatment of patients with advanced, unfavorable Hodgkin’s lymphoma (HL).

Patients and Methods: One hundred sixty-three patients achieving complete remission (CR) or partial remission (PR) with four initial courses of doxorubicin, bleomycin, vinblastine, and dacarbazine, or other doxorubicin-containing regimens, were randomly assigned to receive HDT plus ASCT (83 patients) versus four courses of conventional chemotherapy (80 patients). Unfavorable HL was defined as the presence of at least two of the following poor prognostic factors: high lactate dehydrogenase level, large mediastinal mass (greater than at least 33% of the thoracic diameter), more than one extranodal site, low hematocrit level, and inguinal involvement.

Results: At the end of the treatment program, 92% of patients in arm A and 89% in arm B achieved a CR (P = .6). After a median follow-up of 48 months, the 5-year failure-free survival rates were 75% (95% confidence interval [CI], 65 to 85) in arm A and 82% (95% CI, 73 to 90) in arm B (P = .4). The 5-year overall survival rates were 88% (95% CI, 80 to 96) in arm A and 88% (95% CI, 79 to 96) in arm B (P = .99). The 5-year relapse-free survival rates were 88% in arm A (95% CI, 80 to 96) and 94% in arm B (95% CI, 88 to 100), and the difference was not significant (P = .3).

Conclusion: Patients with advanced unfavorable HL achieving CR or PR after four courses of doxorubicin-containing regimens have a favorable outcome with conventional chemotherapy. No benefit from an early intensification with HDT and ASCT was shown.
Metall‐Alkinyl‐σ‐Komplexe: Synthesen und Materialien
Authors: Long Nicholas J. , Williams Charlotte K.
Published: June 2003

Metallalkinylkomplexe bergen eine große Anziehungskraft für die Synthesechemie, die Strukturchemie und die Materialwissenschaften, sodass mittlerweile eine Vielzahl von Reaktionen zur M‐CC‐Verknüpfung mit einer ganzen Skala von Übergangsmetall‐ und Alkinylreagentien entwickelt wurde. Einige Methoden sind breit anwendbar, andere beschränken sich auf ein spezielles Metall oder Substrat. Wegen der linearen Geometrie der Alkinyleinheit und ihrem ungesättigten Charakter sind die Metallalkinyle attraktive Bausteine für molekulare Drähte und polymere metallorganische Materialien, die interessante physikalische Eigenschaften wie flüssigkristallines Verhalten, optische Nichtlinearität, Lumineszenz und elektrische Leitfähigkeit aufweisen können. Dieses einzigartige Spektrum an Eigenschaften steht als treibende Kraft hinter der intensiven Erforschung von Metall‐Alkinyl‐σ‐Komplexen. Die Entwicklung und Fortschritte insbesondere der letzten zehn Jahre werden in diesem Aufsatz zusammengefasst.
Metal Alkynyl σ Complexes: Synthesis and Materials
Authors: Long Nicholas J. , Williams Charlotte K.
Published: June 2003

Metal alkynyl complexes hold a fascination for synthetic chemists, structural chemists, and materials scientists alike. Harnessing the unique overlap of metal and carbon orbitals is a challenge that can be overcome in many ways and hence, there are many synthetic routes toward MCC bond‐forming reactions that utilize a wide variety of transition‐metal and alkynyl reagents. Some methods can be widely applied, while others are specific to a particular metal or compound. The linear geometry of the alkynyl unit and its π‐unsaturated character have led to metal alkynyls becoming attractive building blocks for molecular wires and polymeric organometallic materials, which can possess interesting properties, such as optical nonlinearity, luminescence, liquid crystallinity, and electrical conductivity. A unique, multifaceted approach, often combining talents from all three of the above chemical disciplines, has served as a driving force behind the intense research into the development of metal alkynyl σ complexes, the progress of which, particularly in the last ten years, is summarized in this review.
Specific roles of cyclooxygenase‐1 and cyclooxygenase‐2 in lipopolysaccharide‐induced fever and fos expression in rat brain
Authors: Zhang Yi‐Hong , Lu Jun , Elmquist Joel K. , Saper Clifford B.
Published: June 2003

Fever is a coordinated autonomic, endocrine, and behavioral response mediated by the brain in reaction to inflammatory stimuli. An essential step in transmitting the immune signal to the brain is the formation of prostaglandin E2. Cyclooxygenase (COX) is the critical enzyme in the synthesis of prostaglandins and COX‐2, the inducible form of the enzyme, is markedly induced in cells associated with the cerebral blood vessels and the leptomeninges by immune stimuli such as intravenous administration of lipopolysaccharide (LPS). However, the specific roles of COX‐1, the constitutive form of cyclooxygenase, and COX‐2 in LPS‐induced fever are not well understood. We injected LPS i.v. in combination with either a highly selective COX‐1 (SC‐560) or COX‐2 (SC‐236) inhibitor to determine the effects of each drug on the subsequent fever response and on the pattern of expression of Fos protein in the brain. The COX‐2 inhibitor blocked LPS‐induced fever and Fos expression in sites such as the ventromedial preoptic nucleus (VMPO) and the hypothalamic paraventricular nucleus (PVH), although Fos‐immunoreactivity in the nucleus of the solitary tract (NTS), ventrolateral medulla (VLM), and parabrachial nucleus (PB) remained. In contrast, the COX‐1 inhibitor resulted in a profound hypothermic response to LPS and blocked LPS‐induced Fos‐immunoreactivity in the PVH, PB, NTS, and VLM, although it had no effect on the VMPO. Although COX‐2 plays a dominant role in mediating fever responses to i.v. LPS, at least some components of the response, including avoiding hypothermia and the induction of Fos in the NTS, VLM, PB, and PVH, appear to depend on COX‐1. J. Comp. Neurol. 463:3–12, 2003. © 2003 Wiley‐Liss, Inc.
Reelin‐immunoreactive neurons, axons, and neuropil in the adult ferret brain: Evidence for axonal secretion of reelin in long axonal pathways
Authors: Martínez‐Cerdeño Verónica , Galazo María J. , Clascá Francisco
Published: June 2003

Reelin is a large secretable protein which, when developmentally defective, causes the reeler brain malformation in mice and a recessive form of lissencephaly with cerebellar hypoplasia in humans. In addition, Reelin is heavily expressed throughout the adult brain, although its function/s there are still poorly understood. To gain insight into which adult neuronal circuits may be under the influence of Reelin, we systematically mapped Reelin‐immunoreactive neuronal somata, axons, and neuropil in the brain and brainstem of ferrets. Results show that Reelin immunoreactivity is found in widespread but specific sets of neuronal bodies, axonal tracts, and gray matter neuropil regions. Depending on the region, the immunoreactive neuronal somata correspond to interneurons, projection neurons, or both. Some well‐defined axonal projection systems are immunoreactive, whereas most other white matter tracts are unlabeled. The labeled pathways include, among others, the lateral olfactory tract, the entorhinohippocampal (perforant) pathway, the retroflex bundle, and the stria terminalis. Labeled axons in these tracts contain large numbers of discrete, very small, immunoreactive particles, suggestive of secretory vesicles under the light microscope. The neuropil in the terminal arborization fields of these axons is also heavily immunoreactive. Taken together, our observations are consistent with the notion that some neurons may anterogradely transport Reelin along their axons in large membrane‐bound secretory vesicles (Derer et al. [2001] J. Comp. Neurol. 440:136–143) and secrete it into their terminal arborization fields, which may be quite distant from the somata synthesizing the protein. These findings have implications for identifying where Reelin acts in adult brain circuits. J. Comp. Neurol. 463:92–116, 2003. © 2003 Wiley‐Liss, Inc.
Linguistic expressions of picture information considering connections between pictures
Authors: Iwata Mitsura , Onisawa Takehisa
Published: June 2003

This paper describes the construction of a system for generating linguistic expressions explaining circumstances related to people or objects that appear in multiple pictures as a means of modeling one form of human intellectual information processing. This system outputs linguistic expressions explaining the emotions of a human object, positional relationship between objects, apparent behavior of an animate object, or relationships connecting pictures based on objective information such as the facial expression, position, or size of an object. To implement the system, soft computing techniques such as neural networks, fuzzy reasoning, and case‐based reasoning are used. Neural networks are used to recognize the degree of emotion from the facial expression of a human object, and fuzzy reasoning is used to infer the degree to which an animate object can discern another object. Case‐based reasoning is used to explain the apparent behavior of an object and relationships connecting pictures. Fuzzy sets are used to convert the information that is obtained to the linguistic expressions that are output. Finally, the effectiveness of the system was confirmed by using the constructed system to perform simulations and evaluation experiments. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 86(12): 38–53, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.10141
Volatile components of Centaurea cineraria L. subsp. umbrosa (Lacaita) Pign. and Centaurea napifolia L. (Asteraceae), two species growing wild in Sicily
Authors: Senatore Felice , Rigano Daniela , De Fusco Raffaele , Bruno Maurizio
Published: June 2003

The volatile components of the ﬂowerheads of Centaurea cineraria L. subsp. umbrosa (Lacaita) Pign. and Centaurea napifolia L. were obtained by hydrodistillation and identiﬁed by GC and GC–MS. Altogether 55 components were identiﬁed, mostly sesquiterpenes and hydrocarbons. Copyright © 2003 John Wiley & Sons, Ltd.
The essential oils of Rinorea subintegrifolia O. Ktze and Drypetes gossweileri S. Moore occurring in Gabon
Authors: Agnaniet Huguette , Mounzeo Hortense , Menut Chantal , Bessiere Jean‐Marie , Criton and Marc
Published: June 2003

The essential oils from root bark of Rinorea subintegrifolia (Violaceae) and bark of Drypetes gossweileri (Euphorbiaceae) from Gabon were analysed by GC–FID and GC–MS. The oils were characterized by a high percentage of benzyl cyanide and a minor amount of terpenes (<1.5%). The antioxidant and the antiradical activity of both samples were evaluated. Copyright © 2003 John Wiley & Sons, Ltd.
Compositional analysis of the essential oil of Lallemantia royleana (Benth. in Wall.) Benth. from Iran
Authors: Ghannadi Alireza , Zolfaghari Behzad
Published: June 2003

Water‐distilled essential oil from aerial parts of Lallemantia royleana (Benth. in Wall.) Benth., grown in Isfahan Province, Iran, was analysed by GC and GC–MS. Forty‐six compounds, constituting 94.5% of the total components detected, were identiﬁed. Among them, verbenone (16.4%) and trans‐carveol (9.8%) were the major components of the oil, which was obtained in 0.1% yield. Copyright © 2003 John Wiley & Sons, Ltd.
Relation between brain activation and lexical performance
Authors: Booth James R. , Burman Douglas D. , Meyer Joel R. , Gitelman Darren R. , Parrish Todd B. , Mesulam M. Marsel
Published: June 2003

Functional magnetic resonance imaging (fMRI) was used to determine whether performance on lexical tasks was correlated with cerebral activation patterns. We found that such relationships did exist and that their anatomical distribution reflected the neurocognitive processing routes required by the task. Better performance on intramodal tasks (determining if visual words were spelled the same or if auditory words rhymed) was correlated with more activation in unimodal regions corresponding to the modality of sensory input, namely the fusiform gyrus (BA 37) for written words and the superior temporal gyrus (BA 22) for spoken words. Better performance in tasks requiring cross‐modal conversions (determining if auditory words were spelled the same or if visual words rhymed), on the other hand, was correlated with more activation in posterior heteromodal regions, including the supramarginal gyrus (BA 40) and the angular gyrus (BA 39). Better performance in these cross‐modal tasks was also correlated with greater activation in unimodal regions corresponding to the target modality of the conversion process (i.e., fusiform gyrus for auditory spelling and superior temporal gyrus for visual rhyming). In contrast, performance on the auditory spelling task was inversely correlated with activation in the superior temporal gyrus possibly reflecting a greater emphasis on the properties of the perceptual input rather than on the relevant transmodal conversions. Hum. Brain Mapping 19:155–169, 2003. © 2003 Wiley‐Liss, Inc.
Phonological short‐term memory networks following recovery from Landau and Kleffner syndrome
Authors: Majerus Steve , Laureys Steven , Collette Fabienne , Del Fiore Guy , Degueldre Christian , Luxen André , Van der Linden Martial , Maquet Pierre , Metz‐Lutz Marie‐Noëlle
Published: June 2003

Landau‐Kleffner syndrome (LKS) is a rare acquired aphasia occurring in otherwise healthy children, together with spike‐wave discharges predominating over superior temporal regions and activated by sleep. Although the outcome of language abilities is variable, a residual impairment in verbal short‐term memory (STM) is frequent. This STM deficit might be related to the persistent dysfunction of those temporal lobe regions where epileptic discharges were observed during the active phase of the disorder. We tested this hypothesis by measuring brain activation during immediate serial recall of lists of 4 words, compared to single word repetition, using H215O positron emission tomography (PET), in 3 LKS patients after recovery and in 14 healthy controls. The patients (TG, JPH, and DC) had shown abnormally increased or decreased glucose metabolism in left or right superior temporal gyrus (STG) at different stages during the active phase of their disease. At the time of this study, the patients were 6–10 years from the active phase of LKS. Results showed that Patients JPH and DC had impaired performance in the STM condition, whereas TG showed near normal performance. PET data showed that JPH and DC activated significantly less than controls left and right posterior STG. TG, having near normal STM performance, showed increased activity in the posterior part of the right STG. These data suggest that impaired verbal STM at late outcome of LKS might indeed be related to a persistent decrease of activity in those posterior superior temporal gyri that were involved in the epileptic focus during the active phase. Hum. Brain Mapping 19:133–144, 2003. © 2003 Wiley‐Liss, Inc.
Human‐derived vascular smooth muscle cells produce angiotensin II by changing to the synthetic phenotype
Authors: Hu Wen‐Yang , Fukuda Noboru , Ikeda Yukihiro , Suzuki Ryo , Tahira Yosiko , Takagi Hiroto , Matsumoto Koichi , Kanmatsuse Katsuo , Mugishima Hideo
Published: June 2003

We investigated whether vascular smooth muscle cells (VSMC)‐derived from human produce angiotensin (Ang) II upon change from the contractile phenotype to the synthetic phenotype by incubation with fibronectin (FN). Expression of α‐smooth muscle (SM) actin, apparent in the contractile phenotype, was decreased by FN. Expressions of matrix Gla and osteopontin, apparent in the synthetic phenotype, were increased by FN. Ang II measured by radioimmunoassay (RIA) was significantly increased in human VSMC by FN. Expression of mRNAs for Ang II‐generating proteases cathepsin D, cathepsin G, ACE, and chymase was increased by FN. Expressions of cathepsin D and cathepsin G proteins were also increased by FN. Ang I‐generating activity, which was inhibited by an aspartyl protease inhibitor pepstatin A, was readily detected in the conditioned medium from human VSMC. Antisense oligodeoxynucleotides (ODNs) that hybridize with cathepsin D and cathepsin G significantly inhibited FN‐increased Ang II in conditioned medium and cell extracts. In VSMC conditioned medium, FN‐induced elevation of Ang II was significantly inhibited by temocapril but not by chymostatin. Ang II type 1 receptor antagonist CV11974 completely, and antisense cathepsin D and cathepsin G ODNs partially inhibited the FN‐stimulated growth of human VSMC. These results indicate that the change of homogeneous cultures of human VSMC from the contractile to the synthetic phenotype sequentially increases expression of proteases cathepsin D, cathepsin G, and ACE, production of Ang II and productions of growth factors, culminating in VSMC proliferation. These findings implicate a new mechanism for the pathogenesis of human vascular proliferative diseases. J. Cell. Physiol. 196: 284–292, 2003. © 2003 Wiley‐Liss, Inc.
Angiotensin II activates extracellular signal regulated kinases via protein kinase C and epidermal growth factor receptor in breast cancer cells
Authors: Greco S. , Muscella A. , Elia M.G. , Salvatore P. , Storelli C. , Mazzotta A. , Manca C. , Marsigliante S.
Published: June 2003

Angiotensin II (Ang II) induces, through AT1, intracellular Ca2+ increase in both normal and cancerous breast cells in primary culture (Greco et al., 2002 Cell Calcium 2:1–10). We here show that Ang II stimulated, in a dose‐dependent manner, the 24 h‐proliferation of breast cancer cells in primary culture, induced translocation of protein kinase C (PKC)‐α, ‐β1/2, and δ (but not ‐ε, ‐η, ‐θ, ‐ζ, and ‐ι), and phosphorylated extracellular‐regulated kinases 1 and 2 (ERK1/2). The proliferative effects of Ang II were blocked by the AT1 antagonist, losartan. Also epidermal growth factor (EGF) had mitogenic effects on serum‐starved breast cancer cells since induced cell proliferation after 24 h and phosphorylation of ERK1/2. The Ang II‐induced proliferation of breast cancer cells was reduced by (a) Gö6976, an inhibitor of conventional PKC‐α and ‐β1, (b) AG1478, an inhibitor of the tyrosine kinase of the EGF receptor (EGFR), and (c) downregulation of 1,2‐diacylglycerol‐sensitive PKCs achieved by phorbol 12‐myristate 13‐acetate (PMA). A complete inhibition of the Ang II‐induced cell proliferation was achieved using the inhibitor of the mitogen activated protein kinase kinase (MAPKK or MEK), PD098059, or using Gö6976 together with AG1478. These results indicate that in human primary cultured breast cancer cells AT1 regulates mitogenic signaling pathways by two simultaneous mechanisms, one involving conventional PKCs and the other EGFR transactivation. J. Cell. Physiol. 196: 370–377, 2003. © 2003 Wiley‐Liss, Inc.
Folate uptake in the human intestine: Promoter activity and effect of folate deficiency
Authors: Subramanian Veedamali S. , Chatterjee Nabendu , Said Hamid M.
Published: June 2003

The intestinal folate absorption process occurs via a specialized mechanism that involves the reduced folate carrier (RFC). In humans, multiple variants of the hRFC (driven by multiple promoters) have been identified with variant I being the prominent form expressed in the intestine. While it is known that promoter B (pB) of hRFC drives the expression of this variant, little is known about the minimal region required for basal activity of this promoter in human intestinal epithelial cells. Also not known is whether folate absorption in the human intestine is up‐regulated during folate deficiency (as occur in animal studies), and if so, whether transcriptional mechanisms via activation of hRFC pB are involved in such regulation. To address these issues, we have used deletion constructs of the hRFC pB and determined their activity in two human intestinal epithelial cell lines: the colon‐derived Caco‐2 cells, and the duodenum‐derived HuTu‐80 cells. Our results showed that activity of hRFC pB to be significantly higher in Caco‐2 cells compared to HuTu‐80 cells, a finding that corresponds with a higher level of folate uptake and endogenous hRFC mRNA levels in the former compared to the latter cell type. The minimal region required for basal activity of hRFC pB in Caco‐2 cells was found to be encoded in a sequence between −1088 and −1043, while in HuTu‐80 cells it was encoded in a sequence between −1431 and −1088. Growing Caco‐2 cells in a folate deficient medium led to a significant and specific up‐regulation in folate uptake. This up‐regulation was associated with a parallel increase in hRFC protein and mRNA levels, and in the activity of hRFC pB. The most responsive sequence of pB to the effect of folate deficiency was found to be encoded in a sequence between −2016 and −1431, i.e., outside the minimal region of the pB. These results show that different minimal regions for hRFC pB are utilized by different intestinal epithelial cells. In addition, folate‐deficiency was found to up‐regulate folate uptake by human intestinal epithelial cells and that this regulation involves activation of hRFC pB. J. Cell. Physiol. 196: 403–408, 2003. © 2003 Wiley‐Liss, Inc.
Phenotype modulation in cultures of vascular smooth muscle cells from diabetic rats: Association with increased nitric oxide synthase expression and superoxide anion generation
Authors: Pandolfi Assunta , Grilli Alfredo , Cilli Carlo , Patruno Antonia , Giaccari Andrea , Di Silvestre Sara , De Lutiis Maria Anna , Pellegrini Giuliana , Capani Fabio , Consoli Agostino , Felaco Mario
Published: June 2003

Proliferative modification of vascular smooth muscle cell (vSMC) and impaired bioavailability of nitric oxide (NO) have both been proposed among the mechanisms linking diabetes and atherosclerosis. However, diabetes induced modifications in phenotype and nitric oxide synthase(s) (NOS) expression and activity in vSMC have not been fully characterized. In this study, cell morphology, proliferative response to serum, alpha‐SMactin levels, eNOS expression and activity, cGMP intracellular content, and superoxide anion release were measured in cultures of vSMC obtained from aorta medial layer of ten diabetic (90% pancreatectomy, DR) and ten control (sham surgery, CR) rats. Vascular SMC from DR showed a less evident “hill and valley” culture morphology, increased growth response to serum, greater saturation density, and lower levels of α‐SMactin. In the same cells, as compared to CR cells, eNOS mRNA levels and NOS activity were increased, while intracellular cGMP level was lower and superoxide anion production was significantly greater. These data indicate that chronic hyperglycemia might induce, in the vascular wall, an increased number of vSMC proliferative clones which persist in culture and are associated with increased eNOS expression and activity. However, upregulation of eNOS and increased NO synthesis occur in the presence of a marked concomitant increase of O2− production. Since NO bioavailabilty, as reflected by cGMP levels, was not increased in DR cells, it is tempting to hypothesize that the proliferative phenotype observed in DR cells is associated with a redox imbalance responsible quenching and/or trapping of NO, with the consequent loss of its biological activity. J. Cell. Physiol. 196: 378–385, 2003. © 2003 Wiley‐Liss, Inc.
Nonsurgical diagnosis and management of an inflammatory pseudotumor of the spleen in a child
Authors: Yesildag Ebru , Sarimurat Nuvit , Ince Umit , Numan Firuzan , Buyukunal Cenk
Published: June 2003

Primary splenic tumors in children are rare and usually benign. We report the case of a 7‐year‐old boy with a splenic mass that initially resembled an infectious process. Histopathologic examination of a specimen obtained using sonographically guided Tru‐cut needle biopsy, performed after angiography, revealed an inflammatory pseudotumor of the spleen, an extremely rare benign lesion. The lesion has been managed conservatively with clinical and sonographic follow‐up. This case shows that benign lesions of the spleen can easily be diagnosed using current radiologic and histopathologic techniques without the need for surgery, thus allowing total or even partial splenectomy to be reserved for patients in whom a mass cannot be diagnosed or in whom clinical progression is evident. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:335–338, 2003
Enlarged fetal bladder: Differential diagnosis and outcomes
Authors: Pinette Michael G. , Blackstone Jacquelyn , Wax Joseph R. , Cartin Angelina
Published: June 2003

The sonographic finding of an enlarged fetal bladder may simply be a transitory normal variant, but it may also be secondary to reflux or to obstructive, neurogenic, or myopathic causes. In this report, we describe the cases of 3 fetuses with an enlarged bladder, each of which had a different cause. The first fetus had posterior urethral valve obstruction, the second, a ruptured neurogenic bladder, and the third, megacystic‐microcolon‐intestinal hypoperistalsis syndrome. When sonographic examination reveals an enlarged fetal bladder, the ureter, kidneys, genitalia, and spine should be evaluated carefully. Although sonography is good at identifying urinary tract abnormalities, it often cannot provide the specific diagnosis or cause. We recommend frequent sonographic monitoring to evaluate such fetuses for persistence of or changes in bladder enlargement and for changes in the volume of amniotic fluid because these signs may be indicators of abnormalities of renal function and risk factors for a poor prognosis. Analysis of fetal electrolyte levels can also aid in determining the prognosis and whether the condition is amenable to therapeutic intervention. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:328–334, 2003
Quantitative assessment of fetal bowel echogenicity: Comparison of harmonic, compound, and fundamental sonographic images
Authors: Lee Hak Jong , Cho Jeong Yeon
Published: June 2003

Purpose

The aims of this study were to assess normal fetal bowel echogenicity quantitatively and to compare the levels of bowel echogenicity observed with the use of 3 different sonographic image‐processing techniques—harmonic plus compound imaging, harmonic imaging alone, and fundamental imaging—and 2 different broadband transducers.

Methods

Women with normal singleton second‐trimester fetuses underwent sonographic scanning with both a 2–5‐MHz and a 4–7‐MHz transducer. The use of the 3 imaging techniques and the 2 transducers resulted in 6 types of images: 2–5‐HC (harmonic plus compound images), 2–5‐H (harmonic images), and 2–5‐F (fundamental images), and 4–7‐HC, 4–7‐H, and 4–7‐F images. The relative echogenicities (brightness) of the fetal bowel and iliac bone were measured, and bowel echogenicity ratios (bowel echogenicity/iliac bone echogenicity × 100) were calculated using graphics software. The resulting data were analyzed to evaluate differences in echogenicity ratios between the 6 types of images.

Results

We examined 37 fetuses during the study period. The bowel echogenicity ratios were highest on the images obtained with harmonic and compound—imaging techniques (2–5‐HC, 84.7 ± 23.4%; 4–7‐HC, 98.5 ± 36.4%). The bowel echogenicity ratio for the 2–5‐HC images was significantly higher than those for the 2–5‐H and the 2–5‐F images (p < 0.01 and p < 0.001, respectively), and those for the 4–7‐HC and 4–7‐H images were higher than that for the 4–7‐F images (p < 0.01 for both comparisons).

Conclusions

A sonographic finding of echogenic fetal bowel should be interpreted cautiously because the use of special image‐processing techniques can artificially enhance the apparent level of echogenicity of the bowel. We recommend rescanning without the use of those techniques if the fetal bowel appears to have an increased level of echogenicity. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:302–307, 2003
Color Doppler sonography of orbital and vertebral arteries in migraineurs without aura
Authors: Kara Simay Altan , Erdemoğlu A. Kemal , Karadeniz M. Yasemin , Altınok Deniz
Published: June 2003

Purpose

The objective of this study was to investigate whether the retrobulbar hemodynamics in the ophthalmic (OA), posterior ciliary (PCA), central retinal (CRA), and vertebral (VA) arteries are affected in migraineurs without aura.

Methods

The eyes of migraineurs without aura and those of healthy control subjects were evaluated during both headache and headache‐free periods. Retrobulbar and vertebral blood flow velocities in the OA, PCA, CRA, and the extracranial part of the VA were measured bilaterally using color Doppler sonography. The peak systolic and end‐diastolic flow velocities and the pulsatility (PI) and resistance (RI) indices were determined for all arteries.

Results

In total, we enrolled 30 migraineurs and 31 healthy control subjects. Statistically significant differences between headache‐free migraineurs and control subjects were observed in the PI and RI of both right and left PCAs and in the RI of both right and left CRAs. The PI and RI of the left VA of the migraineurs were significantly lower during both headache and headache‐free periods than were those of the control subjects. Among the migraineurs, the peak systolic and end‐diastolic velocities of the left VA were increased during headache periods relative to those found during the headache‐free periods.

Conclusions

The retrobulbar circulation and flow hemodynamics in the left VA may be altered in both headache and headache‐free periods in migraineurs without aura. The differences found between migraineurs and control subjects may implicate autonomic dysfunction in migraineurs. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:308–314, 2003
Cellular and molecular mechanisms leading to cortical reaction and polyspermy block in mammalian eggs
Authors: Sun Qing‐Yuan
Published: June 2003

Following fusion of sperm and egg, the contents of cortical granules (CG), a kind of special organelle in the egg, release into the perivitelline space (cortical reaction), causing the zona pellucida to become refractory to sperm binding and penetration (zona reaction). Accumulating evidence demonstrates that mammalian cortical reaction is probably mediated by activation of the inositol phosphate (PIP2) cascade. The sperm‐egg fusion, mediated by GTP‐binding protein (G‐protein), may elicit the generation of two second messengers, inositol 1,4,5 triphosphate (IP3) and diacylglycerol (DAG). The former induces Ca2+ release from intracellular stores and the latter activates protein kinase C (PKC), leading to CG exocytosis. Calmodulin‐dependent kinase II (CaMKII) may act as a switch in the transduction of the calcium signal. The CG exudates cause zona sperm receptor modification and zona hardening, and thus block polyspermic penetration. Oolemma modification after sperm‐egg fusion and formation of CG envelope following cortical reaction also contribute to polyspermy block. Microsc. Res. Tech. 61:342–348, 2003. © 2003 Wiley‐Liss, Inc.
Fertilization abnormalities following human in vitro fertilization and intracytoplasmic sperm injection
Authors: Feng H. , Hershlag A.
Published: June 2003

Fertilization abnormalities are commonly encountered following in vitro fertilization. The widespread introduction of assisted fertilization methods has rapidly led to a changes in both the incidence and types of these aberrations. Such abnormalities can be identified by careful morphological evaluation at the early zygote stage, of pronuclei as well as of polar body formation, and may be confirmed by cytogenetic assessment. The recognition and understanding of fertilization abnormalities have led to the development of novel techniques aimed at preventing them, as well as recent bold attempts at correction. Removal of one pronucleus may allow some triploid embryos to revert to a normal diploid stage. These new developments should provide insight into the understanding of parthenogenesis, androgenesis, and gynogenesis in the human. Microsc. Res. Tech. 61:358–361, 2003. © 2003 Wiley‐Liss, Inc.
Sphincter electromyography and multiple system atrophy
Authors: Nahm Frederick , Freeman Roy
Published: June 2003

Electromyographic studies of the sphincter in patients with multiple system atrophy have shown increased duration and polyphasia of motor unit potentials. These electrophysiological markers have been used to argue for the selective degeneration of sacral motor neurons in Onuf's nucleus in patients with multiple system atrophy. Studies comparing sphincter electromyographic changes in patients with multiple system atrophy and Parkinson's disease have shown significant differences between these two patient populations. Despite the controversy surrounding this claim, recent studies using quantitative electromyographic techniques support the view that reinnervation of the anal sphincter muscles may be a useful diagnostic marker for distinguishing multiple system atrophy from Parkinson's disease. A critical review of these data is needed to assess the validity and reliability of electromyographic changes in multiple system atrophy. © 2003 Wiley Periodicals, Inc. Muscle Nerve 28: 18–26, 2003
Knee extensor torque, work, and EMG during subjectively graded dynamic contractions
Authors: Pincivero Danny M. , Dixon Paul T. , Coelho Alan J.
Published: June 2003

We examined knee extensor peak torque, work, and electromyogram (EMG) during dynamic contractions to perceived exertion levels in men and women. Thirty subjects performed three maximal effort isokinetic knee extensions (60 deg.s−1), followed by three contractions to each of nine separate levels of perceived exertion. Surface EMG of the vastus medialis (VM), vastus lateralis (VL), and rectus femoris (RF), and knee extensor peak torque and work were normalized to a percent of each respective value obtained during the maximal effort contractions. The results demonstrated a significant linear increase in voluntary knee extensor peak torque and work across perceived exertion levels. Knee extensor peak torque and work were less than 70%, 80%, and 90% maximal voluntary contraction (MVC) at perceived exertion levels 7, 8, and 9, respectively. A significant increase in VM, VL, and RF muscle EMG was observed across perceived exertion levels 1 through 9, with EMG increase highest for the VL. The findings demonstrate that dynamic contractions guided by perceived exertion are underproduced at relatively high perceptual intensities, and that reliance on VL activation occurs across submaximal torque levels. The overestimation of knee extensor peak torque and work at relatively high perceptual intensities may suggest the presence of a subconscious mechanism aiming to reduce high muscle and joint forces. Muscle Nerve 28: 54–61, 2003
Ethical review of research involving human subjects: When and why is IRB review necessary?
Authors: Wagner Richard M.
Published: June 2003

Requirements for ethical review of research involving human subjects are based on widely accepted international standards that are implemented by various national regulations and institutional policies. In the United States, most human research is reviewed by institutional review boards (IRBs) applying federal standards. Researchers may not realize the variety of studies that should be submitted for review. Studies involving interventions must be reviewed regardless of whether these are standard interventions, nonmedical interventions, or retrospective studies. Quality improvement activities require IRB review if the results may be published. Research use of information from medical records or of biomedical specimens requires review unless no identifiers are recorded. Review must be sought at least annually and whenever the research changes. Even human research that is technically exempt from Federal regulations usually needs to have that exemption certified by someone other than the researcher. Muscle Nerve 28: 27–39, 2003
Analysis of high mass peptides using a novel matrix‐assisted laser desorption/ionisation quadrupole ion trap time‐of‐flight mass spectrometer
Authors: Martin Rachel L. , Brancia Francesco L.
Published: June 2003

A novel matrix‐assisted laser desorption/ionisation quadrupole ion trap time‐of‐flight (MALDI QIT ToF) mass spectrometer has been used to analyse high mass peptide ions exceeding 2000 Da. Human adrenocorticotropic hormone (fragment 18–39) and oxidised bovine insulin chain B were utilised to evaluate the performance of the instrument both in MS and in MS/MS mode. Its ability to efficiently isolate ions and to fragment them using collisionally activated decomposition (CAD) has been demonstrated using mixtures diluted to the low‐femtomole level on target. Additionally, multiple stage mass spectrometry (MS/MS/MS) provides a second‐generation product ion spectrum in which new fragment ions are detected and new stretches of amino acids are identified. Copyright © 2003 John Wiley & Sons, Ltd.
Cluster chemical ionization for improved confidence level in sample identification by gas chromatography/mass spectrometry
Authors: Fialkov Alexander B. , Amirav Aviv
Published: June 2003

Upon the supersonic expansion of helium mixed with vapor from an organic solvent (e.g. methanol), various clusters of the solvent with the sample molecules can be formed. As a result of 70 eV electron ionization of these clusters, cluster chemical ionization (cluster CI) mass spectra are obtained. These spectra are characterized by the combination of EI mass spectra of vibrationally cold molecules in the supersonic molecular beam (cold EI) with CI‐like appearance of abundant protonated molecules, together with satellite peaks corresponding to protonated or non‐protonated clusters of sample compounds with 1–3 solvent molecules. Like CI, cluster CI preferably occurs for polar compounds with high proton affinity. However, in contrast to conventional CI, for non‐polar compounds or those with reduced proton affinity the cluster CI mass spectrum converges to that of cold EI. The appearance of a protonated molecule and its solvent cluster peaks, plus the lack of protonation and cluster satellites for prominent EI fragments, enable the unambiguous identification of the molecular ion. In turn, the insertion of the proper molecular ion into the NIST library search of the cold EI mass spectra eliminates those candidates with incorrect molecular mass and thus significantly increases the confidence level in sample identification. Furthermore, molecular mass identification is of prime importance for the analysis of unknown compounds that are absent in the library. Examples are given with emphasis on the cluster CI analysis of carbamate pesticides, high explosives and unknown samples, to demonstrate the usefulness of Supersonic GC/MS (GC/MS with supersonic molecular beam) in the analysis of these thermally labile compounds. Cluster CI is shown to be a practical ionization method, due to its ease‐of‐use and fast instrumental conversion between EI and cluster CI, which involves the opening of only one valve located at the make‐up gas path. The ease‐of‐use of cluster CI is analogous to that of liquid CI in ion traps with internal ionization, and is in marked contrast to that of CI with most other standard GC/MS systems that require a change of the ion source. Copyright © 2003 John Wiley & Sons, Ltd.
Quantification of isoflavones and lignans in serum using isotope dilution liquid chromatography/tandem mass spectrometry
Authors: Grace Philip B. , Taylor James I. , Botting Nigel P. , Fryatt Tara , Oldfield Mark F. , Al‐Maharik Nawaf , Bingham Sheila A.
Published: June 2003

Phytoestrogens (isoflavones and lignans) are receiving increasing attention due to a potential protective effect against a number of complex diseases. However, in order to investigate these associations, it is necessary to accurately quantify the levels of phytoestrogens in foods and biological fluids. We report an assay for three isoflavones (daidzein, genistein, and glycitein), two metabolites of daidzein (O‐desmethylangolensin and equol), and two lignans (enterodiol and enterolactone) in human serum using electrospray ionisation liquid chromatography/mass spectrometry (LC/MS) with selective reaction monitoring. A simple, highly automated sample preparation procedure requires only 200 μL of sample and utilises one solid‐phase extraction stage. Limits of detection are in the region of 10 pg/mL for all analytes except equol, which had a limit of detection of approximately 100 pg/mL. The method developed is suitable for measuring the concentrations of phytoestrogens in blood samples collected from large epidemiological studies. The results of the analysis of serum samples from 300 men and women living in the UK are reported. Copyright © 2003 John Wiley & Sons, Ltd.
Status and perspectives of capillary optics at a third‐generation synchrotron radiation source
Authors: Vincze L. , Riekel C.
Published: June 2003

Glass capillary optics has been used routinely at the ESRF microfocus beamline for several years. A large fraction of applications has been to solid polymers and biopolymers. Flux densities up to 108 photons s−1µm−2 mA−1 at 13 keV have been obtained for a beam size down to 2 µm fwb (full‐width‐at‐base). By better matching the divergence from the condensing mirror system to the acceptance of the capillary and increasing the brilliance by an undulator optimized to 13 keV, the flux density is expected to increase by up to a factor of 100. A reduction of beam size to about 100 nm by maintaining current flux density levels is in principle possible. Copyright © 2003 John Wiley & Sons, Ltd.
Characterization of a polycapillary lens for use in micro‐XANES experiments
Authors: Proost K. , Vincze L. , Janssens K. , Gao N. , Bulska E. , Schreiner M. , Falkenberg G.
Published: June 2003

Polycapillary lenses permit x‐rays to be focused down to relatively small (<50 µm) beam diameters. A polycapillary device, suitable for focusing of synchrotron radiation, was characterized at beam line L of HASYLAB (Hamburg, Germany). Beam parameters such as beam size, transmission efficiency and gain in flux density were determined as a function of the energy of the primary monochromatic beam entering the polycapillary. At a distance of 4 mm between the lens tip and the sample, the smallest beam diameters were recorded: 30 µm at 7 keV, decreasing to 8 µm at 21 keV. In the energy range from 7 to 15 keV, the transmission efficiency varied between 30 and 45%, while the maximum gain in flux density was calculated to be around 3500. When the energy was changed from 7 to 30 keV, a vertical translation of only 7–8 µm was observed, indicating that this optic is highly suitable for use in µ‐XANES investigations. To illustrate this point, the investigation of paper corrosion due to iron gall inks and the speciation of Ni in environmental particles is described. Copyright © 2003 John Wiley & Sons, Ltd.
Interference and diffraction in capillary x‐ray optics
Authors: Kukhlevsky S. V.
Published: June 2003

The optical guiding of x‐ray radiation by capillary waveguides is analysed by using the Fresnel–Kirchhoff diffraction theory and the method of images. The guiding of the continuous, short‐pulse, coherent, partially coherent and incoherent waves is presented as the diffraction and interference of several x‐ray beams produced in free space by the Fresnel source of the waveguide. Using the Fresnel source properties, the necessary conditions for influence of the diffraction and interference on the output characteristics of the capillary x‐ray optics in the near‐ and far‐field diffraction zones are derived. The experimental data and computer simulations presented confirm the wave optics behaviour of x‐rays under such conditions. Copyright © 2003 John Wiley & Sons, Ltd.