bluuebunny/crossref_metadata_2025 huggingface dataset:
Motor nervous pathway function is impaired after treatment of childhood acute lymphoblastic leukemia: A study with motor evoked potentials*
Authors: Harila‐Saari Arja H. , Huuskonen Usko E.J. , Tolonen Uolevi , Vainionpää Leena K. , Lanning B. Marjatta
Published: August 2002

Background

The objective was to evaluate whether motor nervous pathways are affected when patients are treated for childhood acute lymphoblastic leukemia (ALL).

Procedure

Thirty‐two children with ALL were studied at the end of treatment by means of motor evoked potentials (MEPs) elicited by magnetic stimulation (MS) transcranially and peripherally and underwent a detailed neurological examination. Thirty‐two healthy children matched with them for age, sex, and height served as a control group.

Results

The latencies of the MEPs were significantly prolonged along the entire motor nervous pathway in the patients with ALL compared with the healthy controls, indicating demyelination in the thick motor fibres. The MEP amplitudes of the distal extremities elicited by stimulation at the brachial plexus and LV spinal level were significantly lowered in the patients treated for ALL, also indicating anatomical or functional loss of descending motor fibres and/or muscle fibres. The MEP amplitudes elicited by cortical MS showed wider variation and no clear abnormalities were found. Neurological signs and symptoms were common after treatment: 41% of the patients had depressed deep tendon reflexes, 31% had fine motor difficulties and 63% gross motor difficulties, and 34% had dysdiadochokinesia. The conduction delay within the peripheral nerve was related to the post‐therapeutic interval after administration of vincristine and the lesions within the CNS to the number of injections of intrathecal methotrexate.

Conclusions

The present results show adverse effects of the ALL treatment on the entire motor nervous pathways. In our experience, the measurement of MEPs by MS provides an objective, painless, and practical tool for assessing the treatment‐related neurotoxicity in both the CNS and the peripheral nerves. These disturbances in the motor nervous pathways at the end of treatment raise the question of the long‐term effects of ALL treatment on the motor nerve tracts, and have led us to employ MEPs to study these effects in long‐term survivors of ALL. Med. Pediatr. Oncol. 36:345–351, 2001. © 2001 Wiley‐Liss, Inc.
Effects of high‐dose methotrexate on the hemostatic system in childhood acute lymphoblastic leukemia
Authors: Totan Mehmet , Dagdemir Ayhan , Ak Ali Riza , Albayrak Davut , Kucukoduk Sukru
Published: August 2002

Background

Tromboembolic and hemorrhagic complications are significant causes of death in patients with malignancy. These are well‐known with the use of certain drugs. This study was planned to investigate whether there was any effect of high‐dose methotrexate on the hemostatic system in childhood acute lymphoblastic leukemia.

Procedure

To evaluate the hemostatic system, we investigated coagulation screening tests (prothrombin time, activated partial thromboplastin time, and fibrinogen), coagulation inhibitors (protein C, protein S, and antithrombin III), and fibrinolytic system (fibrin degradation products and tissue plasminogen activator). These parameters were measured in 35 cycles of high dose‐methotrexate (3 g/m2) of 20 childhood acute lymphoblastic leukemia cases at baseline and on days 1 and 7 after the therapy.

Results

We found that high‐dose methotrexate administration adversely affected both the coagulation system (prolonged prothrombin time and activated partial thromboplastin time and decreased fibrinogen levels) and coagulation inhibitors (decreased protein C, protein S, antithrombin III) on day 1 after chemotherapy compared to the baseline values. The hemostatic parameters began to improve on day 7 after chemotherapy, except for fibrin degradation products. Tissue plasminogen activator levels were not changed with the therapy.

Conclusions

Coagulation cascade (prolonged prothrombin time and activated partial thromboplastin time and decreased fibrinogen) and coagulation inhibitors (decreased protein C, protein S, and antithrombin III levels) have been found to be affected by high‐dose methotrexate therapy, but these transient changes did not cause clinical thromboembolic or hemorrhagic complications. Med. Pediatr. Oncol. 36:429–433, 2001. © 2001 Wiley‐Liss, Inc.
Outcome of high‐risk neuroblastoma using a dose intensity approach: Improvement in initial but not in long‐term results
Authors: Castel Victoria , Cañete A. , Navarro S. , García‐Miguel P. , Melero C. , Acha T. , Navajas A. , Badal M.D.
Published: August 2002

Background

Stage 4 and MYCN amplified (MNA) neuroblastoma in children have a poor prognosis. Our aim was to increase initial and long‐term reponse in this population.

Procedure

High‐risk children were studied according to the International Neuroblastoma Staging System, then treated with high‐dose cyclophosphamide and high‐dose carboplatin, followed by surgery and autologous stem cell transplant or maintenance chemotherapy.

Results

From June 1992 to December 1998, 83 children were admitted in the study (72 stage 4> 1 year, 5 stage 4 MNA infants, and 6 MNA stage 3 children); tumor tissue was obtained from 73, MYCN was performed in 65, being amplified in 21 (32%). Induction chemotherapy was administered in the expected time in 35% of patients. Its toxicity was mainly hematologic followed by infections, and there were 3 chemotherapy‐related deaths. Delayed surgery was performed on 60 patients with complete or >90% resection in 80% of cases. Chemotherapy plus surgery produced some response in 90% of patients, 53% were in CR/VGPR; 49 children received autologous SCT, and 16 received maintenance chemotherapy for 9 months. Follow‐up ranges are 1–87 months, mean 30 months. S and EFS at 4 years are 0.33 (SD 0.02).

Conclusions

High‐dose cyclophosphamide and high‐dose carboplatin are effective in the initial treatment of neuroblastoma; combined with surgery they produce some response in most patients. Nevertheless, the CR/VGPR rate reaches only 53%. Survival time has also been prolonged but most patients relapse with metastases. Med Pediatr Oncol 2001;37:537–542. © 2001 Wiley‐Liss, Inc.
17O NMR spectra of some butyltin(IV) acetates
Authors: Lyčka Antonín , Holeček Jaroslav
Published: August 2002

The 17O NMR spectra of 17O isotope‐enriched tributyltin(IV) acetate (1) and dibutyltin(IV) diacetate (2) were recorded in various solvents over wide temperature ranges. Only a single 17O signal was observed for both oxygen atoms of the —COOSn—groups under these experimental conditions, in both non‐coordinating and coordinating solvents. The 17O NMR spectra of tert‐butyl acetate (3) were obtained for comparison. Copyright © 2002 John Wiley & Sons, Ltd.
Optimizing HMQC for ISn spin systems
Authors: Xiang Bosong , Winemiller Mark D. , Briggs Timothy F. , Fuller David J. , Collum David B.
Published: August 2002

A general analysis of the HMQC experiment for ISn nuclear spin systems is described. The optimal condition for setting up the HMQC experiment was derived. At this optimal condition, the expected HMQC signal was maximized and unwanted signals were satisfactorily reduced. The result was confirmed with the HMQC spectra of an organolithium compound. Copyright © 2001 John Wiley & Sons, Ltd.
GIAO/DFT calculated chemical shifts of tautomeric species. 2‐Phenacylpyridines and (Z)‐2‐(2‐hydroxy‐2‐phenylvinyl)pyridines
Authors: Ośmiałowski Borys , Kolehmainen Erkki , Gawinecki Ryszard
Published: August 2002

1H, 13C and 15N NMR chemical shifts for 28 substituted 2‐phenacylpyridines (ketimine forms) and their enolimine tautomers, (Z)‐2‐(2‐hydroxy‐2‐phenylvinyl)pyridines, were calculated via the GIAO/DFT approach. Among four tested methods at the B3LYP level of theory, the 6–311G, 6–311++G and 6–311G** basis sets gave acceptable result for 13C NMR chemical shifts whereas the 6–311++G** basis set was the minimum needed for reproduction of 15N NMR chemical shifts. Satisfactory reproduction of 13C and 15N NMR chemical shifts for different tautomers revealed that intramolecular hydrogen bonding could be modeled reliably by these calculations when the geometry optimizations were done with the HF/3–21G method. Agreements between theoretical and experimental 13C and 15N NMR chemical shifts and also HF/3–21G and HF/6–31G** optimized structural parameters with those obtained by x‐ray crystallographic measurements suggests that it is not necessary to select too sophisticated and CPU time‐intensive methods for geometry optimizations. Copyright © 2001 John Wiley & Sons, Ltd.
Proton chemical shifts in NMR: Part 17. Chemical shifts in alkenes and anisotropic and steric effects of the double bond
Authors: Abraham Raymond J. , Canton Marcos , Griffiths Lee
Published: August 2002

The 1H NMR spectra of a number of alkenes of known geometry were recorded in CDCl3 solution and assigned, namely ethylene, propene, 4‐methylcyclohexene, 1,4‐dimethylcyclohexene, methylene cyclohexane (in CFCl3–CD2Cl2 at 153 K), 5‐methylene‐2‐norbornene, camphene, bicyclopentadiene, styrene and 9‐vinylanthracene. These results together with literature data for other alkenes, i.e. 1,3‐ and 1,4‐cyclohexadiene, norbornene, norbornadiene, bicyclo[2.2.2]oct‐2‐ene and α‐ and β‐pinene, and other data allowed the determination of the olefinic shielding in these molecules. The shielding was analysed in terms of the magnetic anisotropy and steric effects of the double bond together with a model (CHARGE7) for the calculation of the two‐ and three‐bond electronic effects. For the aromatic alkenes ring current and π‐electron effects were included. This analysis showed that the double bond shielding arises from both anisotropic and steric effects. The anisotropy is due to the perpendicular term only with a value of Δχ(CC) of −12.1 × 10−6cm3mol−1. There is also a steric deshielding term of 82.5/r6 (r in Å). The shielding along the π‐axis changes sign from shielding at long range (>2.5 Å) to deshielding at short range (<2 Å). The model gives the first comprehensive calculation of the shielding of the alkene group. For the data set considered (172 proton chemical shifts) ranging from δ=0.48 to 8.39, the r.m.s. error of observed vs calculated shifts was 0.11 ppm. Copyright © 2001 John Wiley & Sons, Ltd.
Structure of a new isobenzofuranone derivative from Nigella sativa Linn
Authors: Joshi B. S. , Singh K. L. , Roy Raja
Published: August 2002

The seeds of Nigella sativa Linn contain a new isobenzofuranone derivative, 5‐hydroxy‐2,2‐dimethyl‐2,8‐dihydro‐6H‐furo[3,4‐g]chromen‐6‐one (1), obtained from the CHCl3 extract. Complete 1H and 13C assignments of the compound were carried out using one‐dimensional steady‐state difference NOE together with HMQC and HMBC experiments. Copyright © 2001 John Wiley & Sons, Ltd.
Complete analysis of the 1H NMR spectra of bicyclo[3.2.0]hept‐2‐en‐6‐one and the 7,7‐dimethyl, 7,7‐dichloro and 7‐endo‐chloro derivatives
Authors: Abraham Raymond J. , Bedford Geoffrey R. , Canton Marcus , Leonard Paul
Published: August 2002

The proton spectra of bicyclo[3.2.0]hept‐2‐en‐6‐one and the 7,7‐dimethyl, 7,7‐dichloro and 7‐endo‐chloro derivatives were analysed and the chemical shifts and coupling constants are reported. Molecular modelling and chemical shift calculations together with the observed couplings show that only minor conformational changes occur on substitution. Copyright © 2001 John Wiley & Sons, Ltd.
Hydroacridines: Part 23.1H and 13C NMR spectra of sym‐octahydroacridine, its 9‐(3‐pyridyl) and 9‐(4‐pyridyl) derivatives and the corresponding N(10)‐oxides. An experimental approach to the diamagnetic anisotropy of the pyridine nucleus
Authors: Potmischil Francisc , Deleanu Călin , Marinescu Maria , Gheorghiu Mircea D.
Published: August 2002

The complete 1H NMR chemical shift assignments of 1,2,3,4,5,6,7,8‐octahydroacridine (1), 1,2,3,4,5,6,7,8‐octahydro‐9‐(3‐pyridyl)acridine (2), 1,2,3,4,5,6,7,8‐octahydro‐9‐(4‐pyridyl)acridine (3) and the corresponding N(10)‐oxides 1a, 2a and 3a, respectively, were achieved on the basis of 400 MHz 1H NMR spectra and proton–proton decoupling, HMQC and NOEDIFF experiments. The spectral data for the above compounds provided the first experimental evidence of the difference in the anisotropy effect of the two non‐symmetrical moieties of the pyridine nucleus, and allowed us to ascertain that the shielding effect of the moiety defined by the C(2′)—N—C(6′) atoms is weaker than that of the C(3′)—C(4′)—C(5′) moiety. The 13C NMR spectra of 1–3 and 1a–3a and the effect of N(10)‐oxidation on the 13C NMR chemical shifts are also discussed. The N‐oxidation of 2 and 3 with m‐chloroperbenzoic acid occurred regiospecifically, affording the N(10)‐oxides 2a and 3a free of N(1′)‐oxide isomers. Copyright © 2002 John Wiley & Sons, Ltd.
A estradiol‐17β receptor in the reproductive system of the female of Octopus vulgaris: Characterization and immunolocalization
Authors: Cosmo Anna Di , Di Cristo Carlo , Paolucci Marina
Published: August 2002

In this study, for the first time we have identified an estradiol‐17β receptor (ER) in the reproductive system of the female of Octopus vulgaris. Scatchard analysis revealed that one binding component with high affinity and low capacity for the ligand was present in the cytosol, but not in the nuclear extract of the ovary and the oviduct. A steroid specificity competition assay showed that 3H‐estradiol‐17β binding activity showed a preference for estradiol‐17β. DNA‐cellulose chromatography confirmed the presence of one 3H‐estradiol‐17β binding component. By using antibodies anti ER (578‐595), we have localized by Western blotting one band of about 70 kDa. ER immunoreactivity has been localized in the nuclei of the follicle cells of the ovary, in the nuclei of the epithelium lining the proximal portion of the oviduct and in the nuclei, and in the cytoplasm of the inner region of the oviducal gland and in the cytoplasm of the outer region of the oviducal gland. These data, taken together, provide evidence that in Octopus vulgaris the ER has biochemical and immunohistochemical characteristics resembling those of ER in vertebrates.Mol. Reprod. Dev. 61: 367–375, 2002. © 2002 Wiley‐Liss, Inc.
DNA topoisomerase II distribution in mouse preimplantation embryos
Authors: St. Pierre Jason , Wright David J. , Rowe Thomas C. , Wright Shirley J.
Published: August 2002

DNA topoisomerase II (topo II) is an essential enzyme that mediates a variety of chromosome activities including DNA replication, transcription, recombination, and chromosome condensation and segregation. Isoform‐specific anti‐topo II antibodies were used to determine the distribution of topo II α and β in mouse gametes and embryos. Immunoblot analysis with two anti‐topo IIα antibodies revealed that a 170 kDa topo IIα band was present in ovary and testis. Mature sperm exhibited an 89 kDa band only, which may be a degradation product of topo IIα. Immunoblots probed with a monoclonal antibody that recognizes both isoforms, showed bands at 170 and 180 kDa, which correspond to topo IIα and β, respectively. An additional 100 kDa band was also present in ovary and testis. Mature sperm did not exhibit staining with this antibody. We also localized topo II in mouse gametes and embryos up to the blastocyst stage using immunofluorescence microscopy. While both isoforms were found in nuclei and nucleoli of germinal vesicle oocytes, topo IIα localized to metaphase chromosomes during meiosis, and only to nucleoli during embryonic interphase. Topo IIβ was absent from chromosomes of metaphase II oocytes, but localized to embryonic interphase nuclei. Both full‐length isoforms were absent from sperm, indicating topo II is stored maternally. These results identify topo II as an important component of mouse oocyte and embryonic chromatin, and suggest its involvement in oocyte maturation and preimplantation embryonic development. The different immunofluorescent staining patterns indicate topo IIα and β may serve different roles during the embryonic cell cycle. Mol. Reprod. Dev. 61: 335–346, 2002. © 2002 Wiley‐Liss, Inc.
Association of MPF, MAPK, and nuclear progression dynamics during activation of young and aged bovine oocytes*
Authors: Tian X. Cindy , Lonergan Patrick , Jeong Being‐Seon , Evans Alexander C.O. , Yang Xiangzhong
Published: August 2002

We have previously shown that bovine oocytes parthenogenetically activated after 40 hours (hr) of in vitro maturation proceed through the cell cycle faster than those after 20 hr of maturation. In the present study, we used this model of different speed of nuclear progression to investigate the correlation of two hallmarks of nuclear events, exit of metaphase arrest and pronuclear formation, with dynamics of MPF and MAPK. Bovine oocytes were matured in vitro for 20 hr (young) or 40 hr (aged) and activated in 7% ethanol followed by incubation in cycloheximide for 0, 0.5, 1, 3, 5, or 7 hr. Activity of MPF and MAPK was lower in aged than young oocytes. The responses to oocyte activation by both the two kinases and nuclear progression were faster in aged than in young oocytes. The activity of MPF declined to undetectable levels (P < 0.05) as early as 0.5 hr after activation in aged oocytes, while this did not happen in young oocytes until 3 hr after activation. The inactivation of MAPK occurred approximately 2 hr earlier in aged oocytes (5 hr post‐activation) than in young oocytes (7 hr post‐activation). Furthermore, the decline in MPF activity preceded that of MAPK in both young and aged oocytes by about 2 hr. The decrease in activity of MPF and MAPK corresponded with the exit from meiosis and pronuclei formation regardless of the speed of nuclear progression. Despite dramatic changes in activity of MPF and MAPK, the levels of Cdc2 and Erk2 proteins were unchanged (P > 0.05) during the first 7 hr of activation. These observations suggest that inactivation of MPF and MAPK are pre‐requisite for the release from metaphase arrest and formation of pronuclei in bovine oocytes. Mol. Reprod. Dev. 62: 132‐138, 2002. © 2002 Wiley‐Liss, Inc.
Betaine is a highly effective organic osmolyte but does not appear to be transported by established organic osmolyte transporters in mouse embryos
Authors: Hammer Mary‐Anne , Baltz Jay M.
Published: August 2002

Betaine protects early preimplantation mouse embryos against increased osmolarity in vitro, functioning as an organic osmolyte. Betaine is effective at very low external concentrations, with half‐maximal protection of 1‐cell embryo development to blastocysts at approximately 50 μM, making it one of the best osmoprotectants for mouse preimplantation embryos. We performed studies designed to determine whether known high‐affinity organic osmolyte transporters could account for the ability of betaine to act as an organic osmolyte in preimplantation embryos. We found no evidence in 1‐cell embryos of transport by a betaine/GABA transporter (BGT1), the osmoregulated betaine transporter found in a number of cell types, as betaine and GABA did not inhibit each other's transport. Instead, all saturable GABA transport in embryos was apparently via the β‐amino acid transporter. We also found that the glycine transporter, GLY, which mediates osmoprotective transport of glycine in early preimplantation embryos, does not appear to transport betaine. Finally, increased osmolarity did not induce any detectable System A amino acid transporter activity, which is osmotically‐inducible in other cells and can transport betaine. There does appear, however, to be a saturable betaine transporter in 1‐cell mouse embryos, as considerable 14C‐betaine transport was measured which was substantially inhibited by excess unlabeled betaine. Our data imply that betaine functions as an organic osmolyte in embryos due to its saturable transport via a mechanism distinct from known osmolyte transporters. We propose that an unidentified high‐affinity betaine transporter may be expressed in early embryos and mediate transport of betaine as an organic osmolyte. Mol. Reprod. Dev. 62: 195–202, 2002. © 2002 Wiley‐Liss, Inc.
A novel asparaginase‐like protein is a sperm autoantigen in rats
Authors: Bush Leigh Ann , Herr John C. , Wolkowicz Michael , Sherman Nicholas E. , Shore Amy , Flickinger Charles J.
Published: August 2002

A novel asparaginase‐like protein (ALP) of spermatozoa was cloned from rat and human testis cDNA libraries on the basis of reactivity with antibodies produced after vasectomy. Although obstruction of the male reproductive tract is known to cause an immunologic response, few of the sperm antigens responsible for the generation of autoantibodies have been characterized. We are identifying proteins of interest by coring autoantigenic protein spots from two‐dimensional (2‐D) gels of rat sperm extracts and microsequencing them by mass spectrometry. The peptide sequences from ALP, a 28 kDa, pI 5.7 protein, matched to a single partial length rat EST. These peptide sequences were used to clone a cDNA encoding a novel 333 amino acid open reading frame. The new protein had a similarity to portions of L‐asparaginases of plants (43%) and to glycosylasparaginases in animal cells (32%). Human ALP cDNA was subsequently cloned. It showed 77% identity to the rat ALP sequence and the gene, ASRGL1 (asparaginase‐like 1), mapped to chromosome locus 11q12.3. Purified recombinant rat ALP (rALP), expressed in E. coli, was used to raise polyclonal antiserum in guinea pigs. Two observations verified that the correct protein had been cloned: 1) the anti‐rALP antibody reacted with both rALP and rat sperm; and 2) post‐vasectomy sera bound rALP. Anti‐rALP antibody stained the midpiece of rat and human sperm coincident with staining by MitoTracker Green FM, suggesting that ALP is associated with the mitochondria. Northern analysis revealed that rat ALP message was abundantly expressed in the testis but was also present in heart, brain, liver, skeletal muscle, and kidney. © 2002 Wiley‐Liss, Inc. Mol. Reprod. Dev. 62: 233–247, 2002. © 2002 Wiley‐Liss, Inc.
Stage‐specific expression of proprotein form of hyaluronan binding protein 1 (HABP1) during spermatogenesis in rat
Authors: Bharadwaj Archana , Ghosh Ilora , Sengupta Aniruddha , Cooper Trevor G. , Weinbauer Gerhard F. , Brinkworth Martin H. , Nieschlag Eberhard , Datta Kasturi
Published: August 2002

The presence of the 34‐kDa hyaluronan binding protein 1 (HABP1) on sperm surface and its role in fertilization is already established (Ranganathan et al., 1994: Mol Reprod Dev 38:69–76). In the present communication, we examined the expression of HABP1 in adult rat testis during spermatogenesis. Interestingly, using anti‐rHABP1 antibody, we detected a protein of 55 kDa which was present only in testis, but not in other somatic tissues like spleen and liver. However, even in testis, only one transcript of HABP1 mRNA of 1.63 kb was observed. In addition, we confirm that this testis‐specific 55 kDa protein was immunologically identical with proprotein form of HABP1 using antibody raised against a decapeptide present in the proprotein region of HABP1. Comparative immunohistochemistry of testis, spleen, and liver tissues using both the antibodies supported the observation that the proprotein form of HABP1 is present only in testis. Higher mRNA expression of HABP1 in testis as compared to that of liver and spleen could be speculated from the RT‐PCR product. Finally, detailed study of the immunohistochemical staining of the seminiferous tubules revealed the expression of the HABP1 proprotein in specific stages of germ cells, like pachytene spermatocytes and round spermatids, but not in elongated ones, suggesting a possible role of HABP1 proprotein in spermatogenic differentiation. Mol. Reprod. Dev. 62: 223–232, 2002. © 2002 Wiley‐Liss, Inc.
Control of trophectoderm differentiation by inner cell mass‐derived fibroblast growth factor‐4 in mouse blastocysts and corrective effect of fgf‐4 on high glucose‐induced trophoblast disruption
Authors: Leunda‐Casi Amaya , de Hertogh René , Pampfer Serge
Published: August 2002

Previous studies have suggested that fibroblast growth factor‐4 (FGF‐4) may be a paracrine signal used by inner cell mass (ICM) cells to maintain adjacent trophectoderm (TE) cells in an undifferentiated state. In the present work, immunocytochemical analysis of mouse blastocysts confirmed that FGF‐4 was predominantly detected in the ICM before and after spreading over a fibronectin‐coated culture substrate. Addition of human recombinant FGF‐4 did not influence morphological progression, cell allocation and proliferation in ICM and TE lineages or mitosis and karyorhexis frequencies during blastocyst expansion. Addition of FGF‐4 to outgrowing blastocysts, in contrast, induced a significant decrease in the surface of the trophoblast outgrowths formed by the TE cells and in the proportion of giant trophoblasts per outgrowth. The fact that blastocysts display excessive trophoblast expansion and spreading over their culture substrate upon pre‐exposure to high concentrations of glucose in vitro was used to further assess the regulatory effect of FGF‐4. Addition of FGF‐4 was indeed found to fully neutralize the disruptive impact of high glucose on trophoblast outgrowths. Altogether, our data indicate that ICM‐derived FGF‐4 participates actively in the regulation of trophoblast development. Mol. Reprod. Dev. 60: 38–46, 2001. © 2001 Wiley‐Liss, Inc.
mt1 Receptor‐mediated antiproliferative effects of melatonin on the rat uterine antimesometrial stromal cells
Authors: Zhao Hang , Pang Shiu F. , Poon Angela M.S.
Published: August 2002

It has been shown that melatonin regulates uterine function. Our previous studies have demonstrated the presence of melatonin receptors in the rat uterine endometrium, indicating that melatonin may act directly on the uterus. In the present study, the histological localization of the rat uterine melatonin binding was revealed by autoradiography and the molecular subtyping was studied by in situ hybridization in the stromal cells. The signal transduction process and effects of melatonin on stromal cell proliferation was also investigated. Our autoradiograms showed that 2[125I]iodomelatonin binding sites were localized in the antimesometrial endometrial stroma. In situ hybridization with specific mt1 receptor cDNA probe in the primary culture of antimesometrial stromal cells demonstrated the expression of mt1 receptor mRNAs. Melatonin dose‐dependently inhibited forskolin‐stimulated cAMP accumulation, which was reversed by pertussis toxin. This indicates that the rat uterine melatonin receptors are negatively coupled to adenylate cyclase via pertussis toxin sensitive Gi protein. Melatonin also inhibited the incorporation of [3H]thymidine in the rat uterine antimesometrial stromal cells, showing that melatonin has an anti‐proliferative effect on the uterus. Our results suggest that melatonin may act directly on the mt1 melatonin receptors in the rat uterine antimesometrial stromal cells to inhibit their proliferation. Its action may be mediated through a pertussis toxin‐sensitive adenylate cyclase coupled Gi‐protein. Mol. Reprod. Dev. 61: 192–199, 2002. © 2002 Wiley‐Liss, Inc.
Living with support in the community: Predictors of choice and self‐determination
Authors: Stancliffe Roger J.
Published: August 2002

Ensuring that people with intellectual disability experience typical levels of choice and self‐determination has become an essential objective for quality disability services. Three perspectives on self‐determination were identified in the literature: psycho‐educational, ecological, and socio‐political. Personal characteristics, specific self‐determination competencies, and environmental variables all were found to be associated with choice and self‐determination. Living environments that were smaller and more individualized were linked to greater choice and self‐determination. The theoretical perspective investigators applied to the issues influenced approaches to research and intervention, and differences in emphasis were evident regarding the relative importance of self‐determination competencies and environmental factors. MRDD Research Reviews 7:91–98, 2001. © 2001 Wiley‐Liss, Inc.
Renal T perfusion using an iron oxide nanoparticle contrast agent—influence of T1 relaxation on the first‐pass response
Authors: Bjørnerud Atle , Johansson Lars O. , Ahlström Håkan K.
Published: August 2002

Quantitative perfusion measurements require accurate knowledge of the correlation between first‐pass signal changes and the corresponding tracer concentration in tissue. In the present study, a detailed analysis of first‐pass renal cortical changes in T1 and T following bolus injection of the iron oxide nanoparticle NC100150 Injection was investigated in a pig model using a double‐echo gradient‐echo sequence. The estimated change in 1/T during first pass calculated from single‐echo sequences was compared to the true double‐echo‐derived 1/T curves. Using a single‐echo (TE = 6 ms) spoiled gradient‐echo sequence, the first‐pass 1/T response following a bolus injection of 1 mg Fe/kg of NC100150 Injection was significantly underestimated due to counteracting T1 effects. Signal response simulations showed that the relative error in the first‐pass response decreased with increasing TE and contrast agent dose. However, both the maximum TE and the maximum dose are limited by excessive cortical signal loss, and the maximum TE is further limited by high temporal resolution requirements. The problem of T1 contamination can effectively be overcome by using a double‐echo gradient‐echo sequence. This yields a first‐pass response that truly reflects the tissue tracer concentration, which is a critical requirement for quantitative renal perfusion assessment. Magn Reson Med 47:298–304, 2002. © 2002 Wiley‐Liss, Inc.
Human rectal adenocarcinoma: Demonstration of 1H‐MR spectra in vivo at 1.5 T
Authors: Dzik‐Jurasz A.S.K. , Murphy P.S. , George M. , Prock T. , Collins D.J. , Swift I. , Leach M.O. , Rowland I.J.
Published: August 2002

This study was designed to determine whether 1H‐MR spectra of locally advanced human rectal adenocarcinoma could be acquired in vivo at 1.5 T. Despite the relatively large size of these neoplasms, only six out of 21 tumors accommodated a voxel size of 8 cm3. This was due to air pockets within the tumor mass, which limited voxel positioning. Localized proton spectra were acquired at short (20 ms) and long (135 ms) echo times (TEs) using a single‐voxel technique. The most commonly detected metabolites were choline and lipid. Magn Reson Med 47:809–811, 2002. © 2002 Wiley‐Liss, Inc.
Imaging the changes in renal T1 induced by the inhalation of pure oxygen: A feasibility study
Authors: Jones Richard A. , Ries Mario , Moonen Chrit T.W. , Grenier Nicolas
Published: August 2002

The effect of the inhalation of pure oxygen on the kidney was evaluated by measuring monoexponential T1 and T relaxation times in nine volunteers using a multiple‐shot turbo spin echo and multiple echo gradient echo sequences, respectively. The T1 of the renal cortex decreased significantly when breathing pure oxygen as compared to normoxia (from 882 ± 59 to 829 ± 70 msec, P < 0.05), while that of the renal medulla was unchanged. No significant changes were seen in the T of either compartment. Dynamic imaging using an inversion recovery sequence with an optimized inversion time typically produced signal changes of 20% in the renal cortex. Studies to assess if oxygen‐induced changes in flow contributed to this effect showed that the flow contribution was not significant. Although longer inversion times (880 ms) produced optimal contrast, acceptable contrast was also obtained at shorter inversion times (450 msec) in the renal cortex, spleen, and lung, with the latter being of opposite polarity to the other two tissues, implying a shorter parenchymal T1 than previously reported in the literature. The results are consistent with oxygen acting as an intravascular contrast agent which induces a shortening of T1 in the arterial blood volume. Magn Reson Med 47:728–735, 2002. © 2002 Wiley‐Liss, Inc.
Analysis of wave behavior in lossy dielectric samples at high field
Authors: Yang Qing X. , Wang Jinghua , Zhang Xiaoliang , Collins Christopher M. , Smith Michael B. , Liu Haiying , Zhu Xiao‐Hong , Vaughan J. Thomas , Ugurbil Kamil , Chen Wei
Published: August 2002

Radiofrequency (RF) field wave behavior and associated nonuniform image intensity at high magnetic field strengths are examined experimentally and numerically. The RF field produced by a 10‐cm‐diameter surface coil at 300 MHz is evaluated in a 16‐cm‐diameter spherical phantom with variable salinity, and in the human head. Temporal progression of the RF field indicates that the standing wave and associated dielectric resonance occurring in a pure water phantom near 300 MHz is greatly dampened in the human head due to the strong decay of the electromagnetic wave. The characteristic image intensity distribution in the human head is the result of spatial phase distribution and amplitude modulation by the interference of the RF traveling waves determined by a given sample‐coil configuration. The numerical calculation method is validated with experimental results. The general behavior of the RF field with respect to the average brain electrical properties in a frequency range of 42–350 MHz is also analyzed. Magn Reson Med 47:982–989, 2002. © 2002 Wiley‐Liss, Inc.
Two‐component diffusion tensor MRI of isolated perfused hearts
Authors: Hsu Edward W. , Buckley David L. , Bui Jonathan D. , Blackband Stephen J. , Forder John R.
Published: August 2002

Nonmonoexponential MR diffusion decay behavior has been observed at high diffusion‐weighting strengths for cell aggregates and tissues, including the myocardium; however, implications for myocardial MR diffusion tensor imaging are largely unknown. In this study, a slow‐exchange‐limit, two‐component diffusion tensor model was fitted to diffusion‐weighted images obtained in isolated, perfused rat hearts. Results indicate that there are at least two distinct components of anisotropic diffusion, characterized by a “fast” component whose principal diffusivity is comparable to that of the perfusate, and a highly anisotropic “slow” component. It is speculated that the two components correspond to tissue compartments and have a general agreement with the orientations of anisotropy, or fiber orientations, in the myocardium. Moreover, consideration of previous studies of myocardial diffusion suggests that the presently observed fast component may likely be dominated by diffusion in the vascular space, whereas the slow component may include the intracellular and interstitial compartments. The implications of the results for myocardial fiber orientation mapping and limitations of the current two‐component model used are also discussed. Magn Reson Med 45:1039–1045, 2001. © 2001 Wiley‐Liss, Inc.
Magnetization preparation during the steady state: Fat‐saturated 3D TrueFISP
Authors: Scheffler Klaus , Heid Oliver , Hennig Jürgen
Published: August 2002

A novel fat saturation scheme is proposed which combines spectral fat saturation with a steady‐state 3D true Fast Imaging with Steady Precesson (TrueFISP) sequence. Fat saturation consisted of a conventional frequency‐selective excitation pulse surrounded by spoiler gradients. This saturation block was periodically repeated within a continuously running TrueFISP sequence. Except for the fat signals, the steady‐state signal formation and the resulting image contrast of TrueFISP was not modified by the periodically inserted fat saturation block. This was achieved by a α/2 flip‐back pulse before the fat saturation block, which stores the established steady‐state transverse magnetization as pure longitudinal magnetization. After fat saturation this longitudinal magnetization was excited by a α/2 preparation pulse to continue the TrueFISP acquisition. The resulting images show contrast identical to conventional TrueFISP images, but without the usually very bright fat signals. The short repetition time allows acquisition of a 3D data set of the abdomen within a single breath‐hold. Magn Reson Med 45:1075–1080, 2001. © 2001 Wiley‐Liss, Inc.
Chemical shift imaging with spectrum modeling
Authors: An Li , Xiang Qing‐San
Published: August 2002

A new chemical shift imaging technique was developed to efficiently obtain separate images for multiple chemical shift peaks from a set of spin‐echo acquisitions. Information from localized NMR spectroscopy was used to model the chemical shift spectrum as sharp peaks with known resonance frequencies but unknown amplitudes. Based on this model, a set of spin‐echo images with shifted 180° RF pulses were acquired, in which the magnetization vectors of different chemical components were put into different directions. The amplitudes of the chemical shift peaks were obtained by solving nonlinear equations in a region‐growing process. Experimental results on an ethanol phantom as well as a subject with silicone breast implants are presented. Magn Reson Med 46:126–130, 2001. © 2001 Wiley‐Liss, Inc.
Theoretical analysis of the effect of imperfect slice profiles on tagging schemes for pulsed arterial spin labeling MRI
Authors: Keilholz‐George Shella D. , Knight‐Scott Jack , Berr Stuart S.
Published: August 2002

Pulsed arterial spin labeling (ASL) techniques provide a noninvasive method of obtaining qualitative and quantitative perfusion images with MRI. ASL techniques employ inversion recovery and/or saturation recovery to induce perfusion weighting, and thus the performance of these techniques is dependent on the slice profiles of the inversion or saturation pulses. This article systematically examines through simulations the effects of slice profile imperfections on the perfusion signal for nine labeling schemes, including FAIR, FAIRER, and EST (UNFAIR). Each sequence is evaluated for quantitative accuracy, suppression of stationary signal, and magnitude of perfusion signal. Perfusion effects are modeled from a modified Bloch equation and experimentally determined slice profiles. The results show that FAIR, FAIRER, and EST have excellent tissue suppression. The magnitude of the perfusion signal is comparable for FAIR and FAIRER, with EST providing a slightly weaker signal. For quantitative measurements, all three methods underestimate the perfusion signal by more than 20%. Of the additional six ASL techniques examined, only one performed well in this model. This method, which combines inversion and saturation recovery, yields improved signal accuracy (<15% difference from the theoretical value) and tissue suppression similar to that of FAIR and its variants, but has only half the signal. Magn Reson Med 46:141–148, 2001. © 2001 Wiley‐Liss, Inc.
Bicuculline‐induced brain activation in mice detected by functional magnetic resonance imaging
Authors: Mueggler Thomas , Baumann Diana , Rausch Martin , Rudin Markus
Published: August 2002

Dynamic measurements of local changes in relative cerebral blood volume (CBVrel) during a pharmacological stimulation paradigm were performed in mice. Using magnetite nanoparticles as an intravascular contrast agent, high‐resolution CBVrel maps were obtained. Intravenous administration of the GABAA antagonist bicuculline prompted increases in local CBVrel as assessed by MRI with a high spatial resolution of 0.2 × 0.2 mm2 and a temporal resolution of 21 s. Signal changes occurred 20–30 s after the onset of drug infusion in the somatosensory and motor cortex, followed by other cortical and subcortical structures. The magnitudes of the CBVrel increases were 18% ± 4%, 46% ± 14%, and 67% ± 7%, as compared to prestimulation values for the cortex, and 9% ± 3%, 25% ± 4%, and 36% ± 7% for the caudate putamen for bicuculline doses of 0.6, 1.25, and 1.5 mg/kg, respectively. On‐line monitoring of transcutaneous carbon dioxide tension PtcCO2 reflecting arterial PaCO2 did not show any alteration during the stimulation paradigm. One of five of the mice receiving the highest bicuculline dose, and three of seven receiving the intermediate dose displayed a different cortical response pattern. After a CBVrel increase of 40% lasting for approximately 1 min, significant CBVrelreductions by 80% have been observed. Subcortical structures did not display this behavior. The present study suggests that this noninvasive approach of functional MRI (fMRI) can be applied to study drug‐induced brain activation by central nervous system (CNS) drugs in mice under normal and pathological situations. Magn Reson Med 46:292–298, 2001. © 2001 Wiley‐Liss, Inc.
Theoretical analysis of the effects of noise on diffusion tensor imaging
Authors: Anderson Adam W.
Published: August 2002

A theoretical framework is presented for understanding the effects of noise on estimates of the eigenvalues and eigenvectors of the diffusion tensor at moderate to high signal‐to‐noise ratios. Image noise produces a random perturbation of the diffusion tensor. Power series solutions to the eigenvalue equation are used to evaluate the effects of the perturbation to second order. It is shown that in anisotropic systems the expectation value of the largest eigenvalue is overestimated and the lowest eigenvalue is underestimated. Hence, diffusion anisotropy is overestimated in general. This result is independent of eigenvalue sorting bias. Furthermore, averaging eigenvalues over a region of interest produces greater bias than averaging tensors prior to diagonalization. Finally, eigenvector noise is shown to depend on the eigenvalue contrast and imposes a theoretical limit on the accuracy of simple fiber tracking schemes. The theoretical results are shown to agree with Monte Carlo simulations. Magn Reson Med 46:1174–1188, 2001. © 2001 Wiley‐Liss, Inc.
Detection and prevalence of α‐latrotoxin–like effects of serum from patients with Guillain–Barré syndrome
Authors: Jacobs Bart C. , Bullens Roland W.M. , O'Hanlon Graham M. , Ang C. Wim , Willison Hugh J. , Plomp Jaap J.
Published: August 2002

Anti‐GQ1b antibodies are associated with the Miller Fisher syndrome (MFS), a variant of the Guillain–Barré syndrome (GBS). In the ex vivo mouse diaphragm, anti‐GQ1b–positive MFS serum induces muscle fiber twitching, a temporary dramatic increase of spontaneous quantal acetylcholine release, and transmission blockade at neuromuscular junctions (NMJs). These effects resemble those of α‐latrotoxin (α‐LTx) and are induced by antibody‐mediated activation of complement. We developed an assay for detection of the α‐LTx–like effect, using muscle fiber twitching as indicator. We tested 89 serum samples from GBS, MFS, and control subjects, and studied correlations with clinical signs, anti‐ganglioside antibodies, micro‐electrode physiology, and complement deposition at NMJs. Twitching was observed with 76% of the MFS and 10% of the GBS samples. It was associated with ophthalmoplegia and anti‐GQ1b antibodies in patients, and with increased spontaneous acetylcholine release and C3c‐deposition at mouse NMJs. This study strongly suggests that antibodies to GQ1b (with cross‐reactivity to related gangliosides) are responsible for the α‐LTx–like activity. The twitching assay is an efficient test for detection of this effect, and allows for screening of large numbers of samples and modifying drugs. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000–000, 2002
Muscle strength following direct injection of doxorubicin into rabbit sternocleidomastoid muscle in situ
Authors: Falkenberg Jon H. , Iaizzo Paul A. , McLoon Linda K.
Published: August 2002

Direct intramuscular injection of doxorubicin results in permanent myofiber loss. A previous phase I trial demonstrated that such injections could successfully treat blepharospasm and hemifacial spasm. Our previous in vitro study demonstrated that doxorubicin resulted in a dose‐dependent reduction in isometric force generation in sternocleidomastoid muscle in rabbits. This present study examined alterations in force generation in these treated muscles in situ, i.e., with the blood and nerve supply intact. Two months after a single doxorubicin injection, functional changes in peak twitch, tetanic force generation, and fatigue rate were assessed in control and doxorubicin‐treated sternocleidomastoid muscles in rabbits. Peak force measurements were reduced in the treated muscles. These reductions in muscle strength were significantly greater at tetanic peak amplitudes. Fatigue rate was not altered by doxorubicin treatment of the sternocleidomastoid muscles. These findings support the potential clinical use of doxorubicin chemomyectomy for the treatment of patients with cervical dystonia. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000–000, 2002
Epidermal nerve fiber density in sensory ganglionopathies: Clinical and neurophysiologic correlations
Authors: Lauria Giuseppe , Sghirlanzoni Angelo , Lombardi Raffaella , Pareyson Davide
Published: August 2002

We assessed the involvement of somatic unmyelinated fibers in sensory ganglionopathies by skin biopsy and quantitative sensory testing (QST). Sixteen patients with ganglionopathy, 16 with axonal neuropathy, and 15 normal controls underwent skin biopsy at the proximal thigh and the distal leg. Intraepidermal nerve fibers (IENF) were immunostained by antiprotein gene product 9.5, and their linear density was quantified under light microscopy. Confocal microscopy studies with double staining of nerve fibers and basement membrane were also performed. Healthy subjects and neuropathy patients showed the typical proximodistal gradient of IENF density; in neuropathies, values were significantly lower at the distal site of the leg, confirming the length‐dependent loss of cutaneous innervation. Conversely, ganglionopathy patients with hyperalgesic symptoms did not show any change of IENF density between the proximal thigh and the distal leg. The distinct pattern of epidermal denervation seen in sensory ganglionopathy reflected the degeneration of somatic unmyelinated fibers in a fashion that was not length‐dependent, which was consistent with both clinical and neurophysiologic observations and supported the diagnosis. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1034–1039, 2001
Who did what? Authorship and contribution in 2001
Authors: Rennie Drummond
Published: August 2002

Numerous examples of irresponsible authorship are associated with the rise in the number of authors per article and with the documented rise in authorship disputes. Multiple co‐investigators have become the norm, and a result is that old concepts of authorship—which, when there was but one author, automatically linked credit with accountability—have eroded. The answer, in the tradition of scientific transparency, is for authors to decide together their individual contributions and disclose these to their readers. This disclosure is now required by many major general medical journals and has been adopted by the International Committee of Medical Journal Editors as the standard. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1274–1277, 2001
Coupled damage and plasticity modelling in transient dynamic analysis of concrete
Authors: Gatuingt Fabrice , Pijaudier‐Cabot Gilles
Published: August 2002

In a concrete structure subjected to an explosion, for example a concrete slab, the material is subjected to various states of stress which lead to many modes of rupture. Closer to the explosive, a state of strong hydrostatic compression is observed. This state of stress produces an irreversible compaction of the material. Away from the zone of explosion, confinement decreases and the material undergoes compression with a state of stress, which is slightly triaxial. Finally, the compression wave can be reflected on a free surface and becomes a tensile wave, which by interaction with the compression wave, produces scabbing. We present, in this paper, a model aimed at describing these three failure modes. It is based on visco‐plasticity and rate dependent damage in which a homogenization method is used in order to include the variation of the material porosity due to compaction. The model predictions are compared with several experiments performed on the same concrete. Computations of split Hopkinson tests on confined concrete, a tensile test with scabbing, and an explosion on a concrete slab are presented. Copyright © 2001 John Wiley & Sons, Ltd.