bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequency of levodopa‐related dyskinesias and motor fluctuations as estimated from the cumulative literature
Authors: Ahlskog J. Eric , Muenter Manfred D.
Published: August 2002

There is no clear consensus regarding the frequency (and hence, the risk), of dyskinesias or motor fluctuations during chronic levodopa therapy for Parkinson's disease (PD). Multiple clinical series have tabulated these frequencies since the advent of levodopa over 30 years ago. We were interested in determining: (1) the aggregate frequency figures in the existing literature; and (2) how clinical series from the early levodopa era, which included patients with longer durations of parkinsonism, compare to more recent (modern era) series.

We searched MEDLINE for all English language publications reporting the cumulative frequency of levodopa‐induced dyskinesias or motor fluctuations during discrete intervals of treatment. This generated 2,478 publications spanning 1966 through September 2000. Papers with appropriate titles or abstracts were reviewed; reference lists from published clinical series were a source of additional papers for review. This ultimately yielded 74 publications with adequate data, relating to 112 intervals of levodopa treatment. Series that included patients with PD‐onset well before levodopa availability (pre‐levodopa era) were separately analyzed from all subsequent series. Series were grouped by duration of levodopa therapy and the median frequencies of dyskinesias and motor fluctuations were tabulated for each group. The data were analyzed both with and without adjustment for the number (N) in each series.

Among series containing pre‐levodopa era patients, the median dyskinesia frequency was already 50% by 5–6 months of treatment. This contrasts with the modern era series where dyskinesias were reported later in treatment. The median dyskinesia frequency was slightly less than 40% by 4–6 years of levodopa therapy among modern era patients. Motor fluctuations (wearing‐off) were not tabulated in most of the early levodopa series. Among modern era reports, motor fluctuations were nil during the first year of levodopa therapy but were experienced by approximately 40% of patients by 4–6 years of treatment. Similar results were found when the analyses were restricted to only prospective studies where levodopa motor complications were targeted outcome measures.

The conclusions reached were: (1) patients from the pre‐levodopa era experienced dyskinesias much earlier during levodopa treatment than modern era patients, perhaps because of longer durations of pre‐existing PD; (2) in the present era, patients treated with levodopa therapy for 4–6 years have approximately a 40% likelihood of experiencing motor fluctuations and a risk of dyskinesias just short of 40%; and (3) these findings represent incident data and the prevalence of clinically important morbidity may be substantially less. © 2001 Movement Disorder Society.
Restless legs syndrome in an Asian population: A study in Singapore
Authors: Tan E.K. , Seah A. , See S.J. , Lim E. , Wong M.C. , Koh K.K.
Published: August 2002

In face‐to‐face interviews, we examined 157 consecutive individuals aged 55 years and older, selected from the general population in Singapore, and 1,000 consecutive individuals aged 21 years and older, from a primary healthcare center. Based on the IRLSSG criteria, the prevalence of restless leg syndrome (RLS) was 0.6% and 0.1%, respectively.
Effect of sleep deprivation on motor performance in patients with Parkinson's disease
Authors: Högl Birgit , Peralta Cecilia , Wetter Thomas C. , Gershanik Oscar , Trenkwalder Claudia
Published: August 2002

Animal research provides evidence that sleep deprivation influences the dopamine system. Knowledge about the effect of sleep deprivation on motor performance in patients with Parkinsons disease is scarce. This study examines the influence of total and partial sleep deprivation compared to normal sleep on motor state and performance in Parkinson's disease. Fifteen nondepressed patients with Parkinson's disease underwent one night of total sleep deprivation (TSD), one night of partial sleep deprivation (PSD) after 3 a.m., and one control night of normal sleep (S), performed in a random, nonconsecutive order. Over a period of 3 hours the following morning, motor evaluations (United Parkinson's Disease Rating Scale, [UPDRS] and tapping rate) were performed before and every 30 minutes after intake of the usual morning dopaminergic drug dose. All patients underwent polysomnography apart from the sleep deprivation protocol. Mean UPDRS motor scores and tapping velocities did not differ significantly after each of the schedules, but a subgroup of four patients improved their motor score after partial sleep deprivation. These data do not confirm previous findings of an overall positive influence of sleep deprivation on motor function in Parkinson's disease. However, the results indicate that different response types to sleep deprivation may exist and that a subgroup of patients could benefit from partial sleep deprivation. © 2001 Movement Disorder Society.
Increased alpha activity in REM sleep in de novo patients with Parkinson's disease
Authors: Wetter Thomas C. , Brunner Hans , Högl Birgit , Yassouridis Alexander , Trenkwalder Claudia , Friess Elisabeth
Published: August 2002

We compared the sleep structure including a quantitative electroencephalographic (EEG) analysis and the frequency of periodic limb movements (PLM) in 17 patients with Parkinson's disease (PD; 10 men, seven women, mean age 65.9 years, mean Hoehn and Yahr stage 1.8) who had never been treated with dopaminergic agents (de novo), and 10 healthy controls (six men, four women, mean age 64.5 years). The REM sleep EEG of the PD patients was characterized by a sustained increase in the high‐theta/alpha (7.8–10.5 Hz) frequency range during the first one‐third (i.e., 11.00 p.m. to 01.40 a.m.) of the night. There was no significant difference in the sleep continuity and sleep architecture as well as in the PLM index between both groups. The analysis of the temporal dynamics of the observed changes suggests a dysregulation of the REM sleep homeostasis in the patients with PD. © 2001 Movement Disorder Society.
Peroxisome proliferator‐activated receptor (PPAR) modulators: Diabetes and beyond*
Authors: Jones A. Brian
Published: August 2002

Peroxisome proliferator‐activated receptors (PPARs) are a class of ligand modulated transcription factors with a prominent role in the regulation of metabolic processes. This report is intended to provide a limited introduction to the PPAR field, sketched with reference to one early series of PPAR ligands. © 2001 John Wiley & Sons, Inc. Med Res Rev, 21, No. 6, 540–552, 2001
Vascularized composite tissue transfers or open fractures with massive soft‐tissue defects in the lower extremities
Authors: Yajima Hiroshi , Tamai Susumu , Kobata Yasunori , Murata Keiichi , Fukui Akihiro , Takakura Yoshinori
Published: August 2002

From 1982 to 1998, we treated 39 patients with type IIIB and IIIC fractures in the lower extremities by vascularized composite tissue transfers. Thirty‐four of the lesions affected the lower leg, and 5 the foot and ankle. The peroneal flap was used in 25 cases, the latissimus dorsi musculocutaneous flap in 12, the scapula flap in 1, and the gracilis muscle flap in 1. In cases with a peroneal flap transfer, 18 cases used osteocutaneous flap with a fibula. Postoperative circulatory disturbances resulted in revision surgery in 9 patients. Eventually, grafting was successful in 37 patients. In patients with a lower leg reconstruction, additional bone grafting was performed in 7 of 16 patients with cutaneous or musculocutaneous flap transfers. No patient with osteocutaneous flap transfers required an additional bone grafting. The mean periods between injury and time to bone union were 11.7 months in patients with cutaneous flap transfers, and 7.5 months in patients with osteocutaneous flap transfers. © 2002 Wiley Liss, Inc. MICROSURGERY 22:114–119 2002
A compact photonic switch based on multimode interference with partial index‐modulation regions
Authors: Lien Chun‐Hung , Lin Hsueh‐Hui , Weng Shih‐Wan , Wang Hung‐Jen , Chang Wen‐Ching
Published: August 2002

In this letter, we propose a novel 3 × 3 photonic switch based on multimode interference. The power switching between multiple output ports are controlled by changing the refractive indices of the index‐modulated regions where such self‐images occurred. For a more realistic design, the switching characteristics for this structure are numerically investigated by the finite‐difference beam propagation method (FD‐BPM). Simulation results less insertion loss and low crosstalk level of −34dB. Moreover, detailed investigations with design rules of MMI structure have been considered. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 33: 174–176, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10268
Concentration of vascular endothelial growth factor (VEGF) in the serum of patients with malignant bone tumors*
Authors: Holzer Gerold , Obermair Andreas , Koschat Martin , Preyer Oliver , Kotz Rainer , Trieb Klemens
Published: August 2002

Background

Vascular endothelial growth factor (VEGF) is recognized as an important stimulator of angiogenesis. Formation of new blood vessels by angiogenic factors occurs in many biological processes, both physiological and pathological, among others in growth of primary solid malignant tumors and metastasis. This implies that the inhibition of angiogenic factors like VEGF would result in a suppression of tumor growth and metastasis formation. The aim of the present study was to compare preoperative serum VEGF levels of patients having malignant bone tumors with healthy controls to identify serum VEGF levels as a tumor marker.

Procedure

Blood sera from patients with high‐grade osteosarcoma (n = 17), chondrosarcoma (n = 4) and Ewing sarcoma (n = 6) were taken at the time of diagnosis before biopsy and compared with sera from 129 healthy persons. To measure VEGF levels in serum, a commercially available ELISA was used (Quantikine Human VEGF Immunoassay; R&D Systems).

Results

The observed geometric mean VEGF levels and 95% confidence intervals are 232.0 pg ml−1 (168.9–318.5) for patients with high‐grade osteosarcoma, 325.5 pg ml−1 (169.3–625.8) for patients with chondrosarcoma, 484.3 pg ml−1 (284.0–826.0) for patients with Ewing sarcoma, as compared to 216.2 pg ml−1 (192.8–242.5) for healthy individuals.

Conclusions

While the sample means for the three groups of sarcoma patients were higher than the respective mean for the healthy controls, only the mean for the group with Ewing sarcoma is statistically significantly higher than the mean for the healthy controls. Despite the significant difference, VEGF levels are not suitable as a marker for Ewing sarcoma. Med. Pediatr. Oncol. 36:601–604, 2001. © 2001 Wiley‐Liss, Inc.
An NMR study of cyclodextrin complexes of the steroidal neuromuscular blocker drug Rocuronium Bromide
Authors: Cameron Kenneth S. , Fletcher Dan , Fielding Lee
Published: August 2002

The interaction of Rocuronium Bromide, and a model steroid Org 7402, with three cyclodextrins (β‐cyclodextrin, γ‐cyclodextrin and Org 25969) was studied by solution state NMR experiments. Stoichiometries and binding constants were determined from 1H chemical shift titrations. All of the systems formed 1 : 1 complexes. Most of the complexes were in fast exchange with unbound species on the NMR time scale, but the most tightly bound complex (Rocuronium Bromide–Org 25969) was in the slow exchange regime. The geometry of the complexes was inferred from 1H and 13C NMR shift changes upon complexation and from intramolecular NOE correlations. Rocuronium Bromide forms a weak complex with β‐cyclodextrin (Ka = 3.3 ± 0.5 × 103 M−1) and no clear picture of the structure of the complex emerges. The complexes with γ‐cyclodextrin (Ka = 1.8 ± 0.2 × 104 M−1) and Org 25969 (Ka > 105 M−1) are true inclusion complexes with the steroid located inside the central void of the cyclodextrin. Copyright © 2002 John Wiley & Sons, Ltd.
1H and 13C NMR spectral assignments for 3,5‐disubstituted tetrahydro‐2H‐ 1,3,5‐thiadiazine‐2‐thione derivatives
Authors: Molero Dolores , Pérez Rolando , Martinez Roberto , Suárez Margarita , Rodriguez Hortensia , Martín Nazario , Seoane Carlos
Published: August 2002

The proton and carbon spectra of 3,5‐disubstituted tetrahydro‐2H‐1,3,5‐thiadiazine‐2‐thione derivatives, prepared by a solid‐phase procedure, are reported. Copyright © 2001 John Wiley & Sons, Ltd.
A 15N NMR investigation of a series of benzotriazinones and related antitumour heterocycles
Authors: Vaughan Keith , Wilman Derry E. V. , Wheelhouse Richard T. , Stevens Malcolm F. G.
Published: August 2002

A series of 3‐substituted 1,2,3‐benzotriazin‐4‐ones, 1 and 2, were synthesized by standard methods and the 15N NMR spectra were recorded. All spectra were obtained using the natural abundance of the nitrogen‐15 isotope. The chemical shifts appear in the normal range for N‐1, N‐2 and N‐3 of the triazine ring, and also correlate with the chemical shifts in the spectra of the imidazolotriazinone, 4, and the imidazolotetrazinone, 5. Significantly, the spectra of 1a, 2 and 4, recorded with full NOE, show inversion of the singlet assigned to N‐3, demonstrating that these compounds exist in the tautomeric form shown. The structure of the 4‐iminobenzotriazinone (3) was confirmed by this 15N NMR analysis. The spectrum shows a signal for the NH‐bearing imino‐nitrogen atom, which is an inverted singlet in the NOE spectrum, whereas the signal from the N‐3 atom of 3 is not inverted in the NOE spectrum. Copyright © 2002 John Wiley & Sons, Ltd.
In vivo versus in vitro oviductal glycoprotein (OGP) association with the zona pellucida (ZP) in the hamster and baboon
Authors: O'Day‐Bowman M.B. , Mavrogianis P.A. , Minshall R.D. , Verhage H.G.
Published: August 2002

The goal of this study was to determine if differences exist between in vivo vs. in vitro OGP association with the ZP and to quantitate those differences. Ovarian oocytes were harvested 12.5 or 27 hr post‐hCG from hyperstimulated hamsters or baboons, respectively. Hamster and baboon ovarian oocytes were incubated in vitro in media ± homologous OGP (100 or 200 μg/100 μl) or in some studies with 100 μl oviductal fluid for 3, 6, or 24 hr at 37°C. Some of the baboon ovarian oocytes were transferred immediately after harvesting to the ampulla of both oviducts using a tom cat catheter and retrieved after a 3 hr in situ incubation. Hamster oviductal oocytes were collected 3, 6, and 24 hr following ovulation. After incubation or oocyte retrieval from the oviduct, cumulus cells were removed, oocytes were washed extensively and binding of OGP to the ZP was examined by immunofluorescence. Fluorescence intensity was quantified using densitometric scanning of photographic negatives with the background of each negative as an internal control. In all studies, OGP association with the ZP was significantly greater in vivo than in vitro (P < 0.05). In vitro OGP association with the ZP did not significantly increase with incubation time or OGP concentration; however, a small nonsignificant increase in OGP association with the ZP in the oviduct was detected over time. Differences did not appear to be due to depletion of OGP from the in vitro incubation media, since Western blot analysis of the media showed that OGP was still present. Although OGP concentration in vivo is unknown, Western blots showed similar intensity comparing 100 μg of OGP media and oviductal fluid. Immunolocalization of OGP using laser confocal microscopy showed regional differences in OGP binding. The outer half of the zona pellucida had significantly more OGP bound than the inner half on oviductal oocytes. No regional differences were detected for in vitro incubated oocytes. In conclusion, OGP association with the ZP is greater in vivo vs. in vitro, suggesting that one must be cautious in designing and evaluating in vitro studies of OGP function. Mol. Reprod. Dev. 62: 248–256, 2002. © 2002 Wiley‐Liss, Inc.
Effects of aromatase inhibition on in vitro follicle and oocyte development analyzed by early preantral mouse follicle culture
Authors: Hu Y. , Cortvrindt R. , Smitz J.
Published: August 2002

In vivo studies on folliculogenesis have documented a relation among intrafollicular steroid content, follicle growth, and oocyte development. This study examined how profound changes in androgen/estrogen ratio would affect mouse in vitro follicular development. Arimidex®, a potent follicular aromatase inhibitor was used for this purpose. Early preantral follicles were cultured for 12 days up to the preovulatory stage. Oocyte's meiotic maturation, spindle and chromosome configurations, in vitro fertilization and preimplantation embryo development were evaluated. Compared to controls, Arimidex reduced E2 concentration in follicle culture medium by a factor 1000, and an expected simultaneous accumulation of testosterone was measured in the conditioned medium. Arimidex treatment provoked a dose‐dependent earlier differentiation of the granulosa cells as judged by an earlier antrallike cavity formation and slightly elevated basal progesterone secretion. Follicle survival exceeded 98% in all groups and all follicles responded normally to HCG/EGF addition on day 12 by cumulus mucification. By the HCG ovulatory challenge, progesterone output was reduced in Arimidex supplemented groups suggesting preovulatory luteinization. These results indicate that in vitro mouse follicles can develop normally under very low levels of estrogens and that a local androgen increase by a factor 3 is not atretogenic. Oocyte growth did not differ among culture conditions. Arimidex treatment induced a dose dependent enhancement of GVBD and polar body formation rate in response to HCG at the end of culture. Spindle and chromosome analyses demonstrated that in all groups, 90% of the oocytes which extruded a polar body had also reached the MII stage. While most of the cultured MII oocytes had a normal spindle and well aligned chromosomes, significantly less oocytes were fertilized in the groups cultured in the presence of Arimidex. Once fertilized, however, there was found to be no difference for preimplantation embryo development between controls and Arimidex treatment. These data suggest that in mice a pronounced estrogenic environment is not essential for in vitro folliculogenesis. Drastic changes in the intrafollicular steroid concentrations do not disrupt meiotic maturation nor compromise early preimplantation development, but adversely affect fertilization of in vitro grown oocytes. Mol. Reprod. Dev. 61:549–559, 2002. © 2002 Wiley‐Liss, Inc.
Expression of p53 in luminal and glandular epithelium during the growth and regression of rat uterus during the estrous cycle
Authors: Mendoza‐Rodríguez Carmen Adriana , Merchant‐Larios Horacio , Segura‐Valdez María de Lourdes , Moreno‐Mendoza Norma , Cruz María Esther , Arteaga‐López Paola , Camacho‐Arroyo Ignacio , Dominguez Roberto , Cerbón Marco
Published: August 2002

It has been well recognized that epithelial cells of the rat endometrium cyclically proliferate and die during the estrous cycle. The aim of the present study was to determine p53 expression pattern and correlate it with the the apoptotic pattern of epithelial cells of the rat uterus during the estrous cycle. The p53 mRNA and protein expression pattern was assessed by in situ hybridization and immunohistochemistry. The apoptotic index was determined by using terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and electron microscopy. The highest p53 mRNA content, detected by in situ hybridization, was observed on the metestrus day both in the luminal and the glandular epithelia. During this period both epithelia presented high proliferation. The content of p53 mRNA markedly decreased in the following days, presenting its minimal values on the estrus day. The highest number of p53 immunopositive nuclei, in both the luminal and the glandular epithelia, was also detected on the metestrus day, while the lowest one was found on estrus day. On the proestrus day, p53 protein was predominantly detected in the glandular epithelium. However, on the estrus day, p53 protein was detected both in the nuclei and in the cytoplasm of luminal epithelial cells, predominantly in the cytoplasm. The highest apoptotic index in both the luminal and the glandular epithelia was observed on the estrus day whereas the lowest one was observed on the proestrus day. The apoptotic index values were higher in the luminal than in the glandular epithelia. The overall results indicate that p53 expression at both mRNA and protein levels is higher on the metestrus day when the apoptotic index is low. This suggests that p53 should play an important physiological role during proliferative phases of the estrous cycle in the rat uterus. Mol. Reprod. Dev. 61:445–452, 2002. © 2002 Wiley‐Liss, Inc.
Production of germ‐line chimeras in rainbow trout by blastomere transplantation
Authors: Takeuchi Yutaka , Yoshizaki Goro , Takeuchi Toshio
Published: August 2002

We describe a technique for producing germ‐line chimeric rainbow trout, Oncorhynchus mykiss, by microinjection of the isolated blastomeres. FITC‐labeled donor cells and non‐labeled recipient embryos at various developmental stages between the early blastula and early gastrula stages were used for cell transplantation. The chimera formation rate and the degree of donor cell distribution in recipient embryos were evaluated at both the late gastrula stage (5 days post fertilization (dpf)) and the 40‐somite stage (10 dpf). Among the six combinations of developmental stages of donor and recipient embryos, the combination of midblastula (2.5 dpf) donor cells and early blastula (1.5 dpf) recipient embryos gave the highest chimera formation rate and the best distribution pattern of donor cells. Using this combination, chimeric rainbow trout were produced with donor blastomeres from dominant orange‐colored mutant embryos and wild‐type recipient embryos. Of the 238 chimeric embryos produced, 28 (12%) hatched normally and 14 of the 28 fry (50%) had donor‐derived orange body color. To test for germ‐line transmission of donor cells, gametes obtained from the matured chimeras were fertilized with gametes from wild‐type fish. Of the 19 matured chimeras, 6 (32%) yielded donor‐derived orange‐colored progeny, in addition to wild‐type siblings. The contribution rates of donor cells in the germ‐line ranged from 0.3 to 14%. This technique for producing germ‐line chimeras should be a powerful tool for cell‐mediated gene transfer in rainbow trout. Especially, if body color mutants are used for either donor cells or the host embryos, it will be possible to easily concentrate F1 transgenic embryos derived from transplanted donor cells by body color screening. Mol. Reprod. Dev. 59: 380–389, 2001. © 2001 Wiley‐Liss, Inc.
Production of reactive oxygen species by spermatozoa undergoing cooling, freezing, and thawing
Authors: Chatterjee Suvro , Gagnon Claude
Published: August 2002

In the present study, we provide evidence for the production of reactive oxygen species (ROS) during cryopreservation of bovine spermatozoa. Cooling and thawing of spermatozoa cause an increase in the generation of superoxide radicals. Although nitric oxide production remains unaltered during sperm cooling from 22–4°C, a sudden burst of nitric oxide radicals is observed during thawing. Increase in lipid peroxidation levels have been observed in frozen/thawed spermatozoa and appears to be associated with a reduction in sperm membrane fluidity as detected by spin labeling studies. The data presented provide strong evidence that oxygen free radicals are produced during freezing and thawing of bovine spermatozoa and suggest that these reactive oxygen species may be a cause for the decrease in sperm function following cryopreservation. Mol. Reprod. Dev. 59: 451–458, 2001. © 2001 Wiley‐Liss, Inc.
Family of SRY/Sox proteins is involved in the regulation of the mouse Msh4 (MutS homolog 4) gene expression*
Authors: Santucci‐Darmanin Sabine , Vidal Frédérique , Scimeca Jean‐Claude , Turc‐Carel Claude , Paquis‐Flucklinger Véronique
Published: August 2002

The eukaryotic MutHLS‐like system plays a crucial role in both mitosis and meiosis. Until now, a number of works have focused on the function of MutS and MutL homologs during mismatch DNA repair. Nevertheless, little is known about the role of these proteins during meiosis. MSH4 is a meiosis specific protein that is necessary for meiotic recombination in Saccharomyces cerevisiae. The human MSH4 protein is only found in testis and ovary. It is involved first in synapsis and second during recombination together with MLH1 (MutL Homolog 1). Here, we report the identification of the mouse Msh4 gene that is located on chromosome 3. We examined the expression of mMsh4 in testes of increasing developmental age and in elutriated germ cells. The pattern of expression during spermatogenesis is consistent with a role for MSH4 both during zygonema and pachynema. We demonstrated a promoter activity of the mMsh4 5′‐flanking region by cell transfection experiments with a luciferase reporter gene. We found several SRY/Sox binding sites in this region and co‐transfection experiments showed that SRY could down regulate mMsh4 promoter transcriptional activity. We propose that the regulation of mMsh4 expression could be one of the reasons for the persistence of SRY and/or SRY‐related proteins in adult testis. Mol. Reprod. Dev. 60: 172–180, 2001. © 2001 Wiley‐Liss, Inc.
Degradation of maternal cdc25c during the maternal to zygotic transition is dependent upon embryonic transcription*
Authors: Anderson Jon E. , Matteri Robert L. , Abeydeera Lalantha R. , Day Billy N. , Prather Randall S.
Published: August 2002

To gain a better understanding of the molecular differences that may contribute to cleavage arrest and the poorer development associated with laboratory produced embryos, a series of experiments were conducted to quantitate the message levels of the cell cycle controller cdc25c, over the maternal to zygotic transition (MZT) in 4‐cell in vivo‐ and in vitro‐derived porcine embryos. The experiments were designed to measure both maternal and embryonic derived cdc25c transcripts by quantitative reverse transcription‐competitive polymerase chain reaction (RT‐cPCR), determine the point of the transition to zygotic genome activation, and study the interaction between initial embryonic transcription and maternal cdc25c degradation. Analysis of in vivo‐ and in vitro‐derived embryos revealed no difference in cdc25c message level for any of the times P4CC (P > 0.05). Comparison of control embryos from 5‐ to 33‐hr P4CC revealed a reduction in transcript quantities in the 10‐hr P4CC group that was maintained at later time points (P < 0.05). Embryos cultured in the RNA polymerase inhibitor, α‐amanitin, from cleavage to 5‐, 10‐, 18‐, 25‐, or 33‐hr P4CC displayed no difference in cdc25c levels when compared to controls at similar time points (P > 0.05). However, if embryos were first exposed to α‐amanitin after 18‐hr P4CC with this treatment continuing to 33 hr, the levels of cdc25c transcript were reduced (P < 0.04) when compared to those embryos that were first exposed to the inhibitor at either 5‐ or 10‐hr P4CC. This finding and the comparison of these same embryos to the 0–33‐hr α‐amanitin and control groups allowed us to conclude that cdc25c transcription began between 10‐ and 18‐hr P4CC, with the degradation of maternal cdc25c message dependent on transcriptional initiation. Mol. Reprod. Dev. 60: 181–188, 2001. © 2001 Wiley‐Liss, Inc.
Production of transgenic mice from vitrified pronuclear‐stage embryos
Authors: Bagis H. , Odaman H. , Sagirkaya H. , Dinnyés A.
Published: August 2002

Cryopreservation of pronuclear‐stage embryos would be useful for transgenic technology and genome preservation purposes. We compared a novel vitrification technique (solid surface vitrification, SSV) with another vitrification method in straws for cryosurvival and to generate transgenic progeny from cryopreserved mouse zygotes following microinjection. The SSV solution consisted of 35% ethylene glycol (EG), 5% polyvinyl‐pyrrolidone (PVP), and 0.4 M trehalose in M2 supplemented with 4 mg/ml BSA; the in straw vitrification solution was 7 M EG in M2 plus BSA. In experiment I, we compared the effect of the vitrification solutions alone, without cooling. No reduction was detected in survival and cleavage rates. In experiment II, SSV yielded a significantly higher percentage of morphologically normal zygotes (96%) that also cleaved at significantly higher rates (80%) when compared to that following “in straw” vitrification (68 and 66%, respectively). Cleavage rate in the non‐vitrified control group (93%) was significantly higher than that of both vitrified groups. Following embryo transfer, there was no difference in the rate of pups obtained from the SSV, “in straw” vitrified, and control groups (97/457, 21%; 15/75, 20% and 56/209, 27%, respectively). In experiment III, SSV vitrified and fresh embryos were used for pronuclear DNA injection. Survival rate of vitrified embryos after microinjection was reduced compared to nonvitrified ones (64 vs. 72%, respectively; P < 0.05); however, development to two‐cell stage was not different (76 vs. 72%, respectively). Following embryo transfer of vitrified vs. fresh microinjected embryos, in both cases 10% live pups were generated, including transgenic pups. The results demonstrated that the efficiency of generating transgenic pups from SSV vitrified pronuclear zygotes is comparable to that from fresh embryos. Mol. Reprod. Dev. 61: 173–179, 2002. © 2002 Wiley‐Liss, Inc.
Down syndrome and Alzheimer's disease: A link between development and aging
Authors: Lott Ira T. , Head Elizabeth
Published: August 2002

A subset of aged individuals with Down syndrome (DS) exhibits the clinical features of Alzheimer's disease (AD) but our ability to detect dementia in this population is hampered by developmental differences as well as the sensitivity of existing test tools. Despite the apparent clinical heterogeneity in aged individuals with DS, age‐associated neuropathology is a consistent feature. This is due to the fact that trisomy 21 leads to a dose‐dependent increase in the production of the amyloid precursor protein and subsequently the production of the amyloidogenic fragments leading to early and predominant senile plaque formation. A review of the existing literature indicates that oxidative damage and neuroinflammation may interact to accelerate the disease process particularly in individuals with DS over the age of 40 years. By combining clinical information with measures of brain‐region specific neuropathology we can “work backwards” and identify the earliest and most sensitive clinical change that may signal the onset of AD. For the past 50 years, investigators in the fields of mental retardation, developmental disabilities, and aging have been interested in the curious link between AD and DS. The morphologic and biochemical origins of AD are seen in the early years of the lifespan for individuals with DS. Study of the process by which AD evolves in DS affords an opportunity to understand an important link between development and aging. This review will focus on advances in the molecular and clinical basis of this association. MRDD Research Reviews 2001;7:172–178. © 2001 Wiley‐Liss, Inc.
Compartmental study of T1 and T2 in rat brain and trigeminal nerve in vivo
Authors: Does Mark D. , Gore John C.
Published: August 2002

The integrated T1–T2 characteristics of rat brain and trigeminal nerve water were studied in vivo using a rapid method for acquiring a series of images that depend on T1 and T2 relaxation times. Gray matter regions showed only one signal component in both the T1 and T2 domains. Trigeminal nerve, however, which has been shown previously to exhibit three T2 components, was found to also exhibit three T1 components. The correlations between these T1 and T2 components were demonstrated by uniquely filtering out each of the three T2 components using an inversion‐recovery preparation, as determined by the component T1 values. Based on previous works, it is postulated that each of these three signal components is derived from a unique microanatomical region of the nerve. Knowledge of these T1 components may thus prove valuable in devising novel methods of identifying the presence and quantifying the volume of tissue subtypes such as myelin. Magn Reson Med 47:274–283, 2002. © 2002 Wiley‐Liss, Inc.
Recovery of function in cytoprotected cerebral cortex in rat stroke model assessed by functional MRI
Authors: Sauter Andre , Reese Torsten , Pórszász Robert , Baumann Diana , Rausch Martin , Rudin Markus
Published: August 2002

Functional recovery in cytoprotected somatosensory cortex in a rat stroke model was studied using functional MRI (fMRI). Calcium antagonist treatment (isradipine) following permanent middle cerebral artery occlusion (pMCAO) reduced the infarct volume by 33 ± 9%. The somatosensory cortex representing the forepaws was spared from infarction; however, cerebral blood flow (CBF) was significantly reduced in this area 24 hr following pMCAO. Neural function was assessed at days 1, 2, 5, and 12 following pMCAO by fMRI using electrical stimulation of both forepaws. Vehicle‐treated rats did not show fMRI responses in the infarcted somatosensory cortex throughout the study. Several of the isradipine‐treated animals displayed functional recovery in the cytoprotected cortex at days 5 (3/5 rats) and 12 (5/10). Correlations with fMRI signals showed that normal T2 and ADC values in the respective brain areas are necessary, but not sufficient prerequisites for functionality. Recovery of neural function is associated with normalization of CBF in the cytoprotected brain area. Magn Reson Med 47:759–765, 2002. © 2002 Wiley‐Liss, Inc.
Blood pool contrast‐enhanced MRI detects suppression of microvascular permeability in early postinfarction reperfusion after nicorandil therapy
Authors: Krombach Gabriele A. , Higgins Charles B. , Chujo Mitsuaki , Saeed Maythem
Published: August 2002

Nicorandil is an adenosine triphosphate‐sensitive potassium channel opener with a nitrate‐like effect. It is approved for clinical use in Europe and Japan as an antianginal drug. The purpose of this investigation was to assess the acute effects of nicorandil therapy on microvascular injury using the blood pool MR contrast medium, NC100150 injection (Clariscan™). Microvascular injury was produced in 24 rats using 45 min of coronary occlusion / 3 hr reperfusion. Nicorandil was infused at 15 min of occlusion and during reperfusion. Control animals received a saline solution. MR imaging was used to characterize microvascular permeability, quantify the extent of microvascular injury, LV volume, and wall thickness. Hyperenhancement at 30 min after administration of 0.05 mmol/kg Clariscan mapped the extent of ischemia‐induced loss of microvascular integrity. The accumulation of Clariscan in the injured region was significantly suppressed in nicorandil compared to control rats. Nicorandil reduced the extent of microvascular injury from 44 ± 2% to 18 ± 2% (P < 0.01) and true infarction size from 29 ± 2% to 12 ± 1%. The extent of the hyperenhanced region correlated with the true size of area at risk at autopsy. On spin‐echo MRI during end‐diastole, nicorandil reduced LV end‐diastolic volume and preserved wall thickness in remote myocardium; both parameters are markers of LV dilatation caused by acute infarction (remodeling). In conclusion, blood pool contrast‐enhanced MRI has the potential to depict and quantify the extent of microvascular permeability and injury. Nicorandil suppressed microvascular permeability, reduced infarction size, and improved LV function in early postinfarction reperfusion. Magn Reson Med 47:896–902, 2002. © 2002 Wiley‐Liss, Inc.
Perfusion‐based high‐resolution functional imaging in the human brain at 7 Tesla
Authors: Pfeuffer Josef , Adriany Gregor , Shmuel Amir , Yacoub Essa , Van De Moortele Pierre‐Francois , Hu Xiaoping , Ugurbil Kamil
Published: August 2002

Perfusion‐based MRI measures cerebral blood flow (CBF) at the capillary level and can be used for functional studies based on the tight spatial coupling between brain activity and blood flow. Obtaining functional CBF maps with high spatial resolution is a major challenge because the CBF signal is intrinsically low and the SNR is critical. In the present work, CBF‐based functional imaging was performed at a considerably smaller voxel size than previously reported in humans. High‐resolution CBF maps were obtained with voxel sizes as small as 0.9 × 0.9 × 1.5 mm3 in the human brain. High sensitivity was made possible by signal‐to‐noise gains at the high magnetic field of 7 T and by using a novel RF combination coil design. In addition, a reduction of the field‐of‐view was critical to achieve 0.9‐mm in‐plane resolution with gradient‐echo echo‐planar imaging in a single shot. Functional CBF data were compared with functional BOLD data to reveal that, for CBF, large contrast‐ to‐noise gains were obtained at high spatial resolution, indicating that the functional CBF response was more localized. High‐resolution functional CBF imaging is significant for neuroscience research because it provides better localization and more specific information than BOLD for monitoring brain function. Magn Reson Med 47:903–911, 2002. © 2002 Wiley‐Liss, Inc.
[1‐13C] glucose MRS in chronic hepatic encephalopathy in man
Authors: Blüml Stefan , Moreno‐Torres Angel , Ross Brian D.
Published: August 2002

[1‐13C]‐labeled glucose was infused intravenously in a single dose of 0.2 g/kg body weight over 15 min in six patients with chronic hepatic encephalopathy, and three controls. Serial 13C MR spectra of the brain were acquired. Patients exhibited the following characteristics relative to normal controls: 1) Cerebral glutamine concentration was increased (12.6 ± 3.8 vs. 6.5 ± 1.9 mmol/kg, P < 0.006) and glutamate was reduced (8.2 ± 1.0 vs. 9.9 ± 0.6 mmol/kg, P < 0.02). 2) 13C incorporation into glutamate C4 and C2 positions was reduced in patients (80 min after start of infusion C4: 0.43 ± 0.09 vs. 0.84 ± 0.15 mmol/kg, P < 0.001; C2: 0.20 ± 0.03 vs. 0.45 ± 0.07 mmol/kg, P < 0.0001). 3) 13C incorporation into bicarbonate was delayed (90 ± 21 vs. 40 ± 10 min, P < 0.003), and the time interval between detection of glutamate C4 and C2 labeling was longer in patients (22 ± 8 vs. 12 ± 3 min, P < 0.03). 4) Glutamate C2 turnover time was reduced in chronic hepatic encephalopathy (17.1 ± 6.8 vs. 49.6 ± 8.7 min, P < 0.0002). 5) 13C accumulation into glutamine C2 relative to its substrate glutamate C2 increased progressively with the severity of clinical symptoms (r = 0.96, P < 0.01). These data indicate disturbed neurotransmitter glutamate/glutamine cycling and reduced glucose oxidation in chronic hepatic encephalopathy. [1‐13C] glucose MRS provides novel insights into disease progression and the pathophysiology of chronic hepatic encephalopathy. Magn Reson Med 45:981–993, 2001. © 2001 Wiley‐Liss, Inc.
Quantitative model for the interecho time dependence of the CPMG relaxation rate in iron‐rich gray matter
Authors: Jensen J.H. , Chandra R. , Yu H.
Published: August 2002

A quantitative model is proposed for computing the dependence on the interecho time of the NMR relaxation rate in iron‐rich gray matter obtained with a Carr‐Purcell‐Meiboom‐Gill sequence. The model consists of representing oligodendrocytes as identical magnetic spheres arranged in a spatially random pattern, and in approximating water diffusion as isotropic and unrestricted. Predictions of the model are calculated numerically using a Monte Carlo technique and, for the weak field limit, using an analytic formula. The model is shown to provide a good fit to experimental measurements of in vitro samples of monkey brain at field levels of 1.0 T and 1.5 T. These field levels are not sufficient to fully determine the model parameters, but it is argued that this may be possible at 3.0 T. The model is potentially of value for multiple‐spin‐echo MRI studies of iron‐related neurodegenerative disorders, such as Parkinson's disease. In particular, the model can be applied to correlate MRI data with the cellular distribution of iron in gray matter. Magn Reson Med 46:159–165, 2001. © 2001 Wiley‐Liss, Inc.
Motoneurons: A preferred firing range across vertebrate species?
Authors: Hornby T. George , McDonagh Jennifer C. , Reinking Robert M. , Stuart Douglas G.
Published: August 2002

The term “preferred firing range” describes a pattern of human motor unit (MU) unitary discharge during a voluntary contraction in which the profile of the spike‐frequency of the MU's compound action potential is dissociated from the profile of the presumed depolarizing pressure exerted on the unit's spinal motoneuron (MN). Such a dissociation has recently been attributed by inference to the presence of a plateau potential (PP) in the active MN. This inference is supported by the qualitative similarities between the firing pattern of human MUs during selected types of relatively brief muscle contraction and that of intracellularly stimulated, PP‐generating cat MNs in a decerebrate preparation, and turtle MNs in an in vitro slice of spinal cord. There are also similarities between the stimulus‐response behavior of intracellularly stimulated turtle MNs and human MUs during the elaboration of a slowly rising voluntary contraction. This review emphasizes that there are a variety of open issues concerning the PP. Nonetheless, a rapidly growing body of comparative vertebrate evidence supports the idea that the PP and other forms of non‐linear MN behavior play a major role in the regulation of muscle force, from the lamprey to the human. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000–000, 2002
The motor cortex and amyotrophic lateral sclerosis
Authors: Eisen Andrew , Weber Markus
Published: August 2002

On theoretical grounds, abnormalities of the motor cortex in patients with amyotrophic lateral sclerosis (ALS) could lead to anterograde (“dying‐forward”) transneuronal degeneration of the anterior horn cells as suggested by Charcot. Conversely, retrograde (“dying‐back”) degeneration of the corticospinal tracts could affect the motor cortex. Evidence derived from clinical, neuropathological, static, and functional imaging, and physiological studies, favors the occurrence of anterograde degeneration. It is hypothesized that transneuronal degeneration in ALS is an active excitotoxic process in which live but dysfunctional corticomotoneurons, originating in the primary motor cortex, drive the anterior horn cell into metabolic deficit. When this is marked, it will result in more rapid and widespread loss of lower motor neurons. In contrast, slow loss of corticomotoneurons, as occurs in primary lateral sclerosis (PLS), precludes excitotoxic drive and is incompatible with anterograde degeneration. Preservation of slow‐conducting non‐M1 direct pathways in PLS is not associated with excitotoxicity, and anterior horn cells survive for long periods of time. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 564–573, 2001
Lidocaine selectively blocks abnormal impulses arising from noninactivating Na channels
Authors: Khodorova Alla , Meissner Konrad , Leeson Stanley , Strichartz Gary R.
Published: August 2002

Abnormal, repetitive impulse firing arising from incomplete inactivation of Na+channels may be involved in several diseases of muscle and nerve, including familial myotonias and neuropathic pain syndromes. Systemic local anesthetics have been shown to have clinical efficacy against myotonias and some forms of neuropathic pain, so we sought to develop an in vitro model to examine the cellular basis for these drugs' effects. In frog sciatic nerves, studied in vitro by the sucrose‐gap method, peptide α‐toxins from sea anemone (ATXII) or scorpion (LQIIa) venom, which inhibit Na+channel inactivation, induced repetitively firing compound action potentials (CAPs) superimposed on a plateau depolarization lasting several seconds. The initial spike of the CAP was unaffected, but the plateau and repetitive firing were strongly suppressed by 5–30 μM lidocaine. Lidocaine caused a rapid, concentration‐dependent decay of the plateau, quantitatively consistent with blockade of open Na+channels. Early and late repetitive firing were equally suppressed by lidocaine with IC50 = 10 μM. After washout of lidocaine and LQIIa, the plateau and repetitive firing remained for > 1 h, showing that lidocaine had not caused dissociation of channel‐bound α‐toxin. These findings indicate that therapeutic concentrations of lidocaine can reverse the “abnormal” features of action potentials caused by non‐inactivating Na+channels without affecting the normal spike component. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 634–647, 2001
Thalidomide neuropathy in patients treated for metastatic prostate cancer
Authors: Molloy F.M. , Floeter M.K. , Syed N.A. , Sandbrink F. , Culcea E. , Steinberg S.M. , Dahut W. , Pluda J. , Kruger E.A. , Reed E. , Figg W.D.
Published: August 2002

We prospectively evaluated thalidomide‐induced neuropathy using electrodiagnostic studies. Sixty‐seven men with metastatic androgen‐independent prostate cancer in an open‐label trial of oral thalidomide underwent neurologic examinations and nerve conduction studies (NCS) prior to and at 3‐month intervals during treatment. NCS included recording of sensory nerve action potentials (SNAPs) from median, radial, ulnar, and sural nerves. SNAP amplitudes for each nerve were expressed as the percentage of its baseline, and the mean of the four was termed the SNAP index. A 40% decline in the SNAP index was considered clinically significant. Thalidomide was discontinued in 55 patients for lack of therapeutic response. Of 67 patients initially enrolled, 24 remained on thalidomide for 3 months, 8 remained at 6 months, and 3 remained at 9 months. Six patients developed neuropathy. Clinical symptoms and a decline in the SNAP index occurred concurrently. Older age and cumulative dose were possible contributing factors. Neuropathy may thus be a common complication of thalidomide in older patients. The SNAP index can be used to monitor peripheral neuropathy, but not for early detection. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1050–1057, 2001
Risk factors for hematological malignancy in polyneuropathy associated with monoclonal gammopathy
Authors: Eurelings Marijke , Notermans Nicolette C. , Van de Donk Niels W.C.J. , Lokhorst Henk M.
Published: August 2002

Polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUS) is a well‐known disease entity. Of the patients with monoclonal gammopathy without neuropathy, 25% develop a hematological malignancy during long‐term follow‐up. Whether the frequency of hematological malignancy is similar in patients with polyneuropathy associated with monoclonal gammopathy and whether hematological screening is necessary in these patients is unknown. To determine the frequency of and risk factors for a hematological malignancy, we investigated 104 patients with polyneuropathy and monoclonal gammopathy. Potential diagnostic variables were obtained from medical history, physical and neurological examination, and laboratory analysis. The associations between potential diagnostic variables and outcome, hematological malignancy, were evaluated by univariable and multivariable logistic‐regression analysis. Among our patients, 23 had a hematological malignancy (8 multiple myeloma, 10 low‐grade lymphoma, 3 plasmacytoma, 1 Castleman's disease and 1 POEMS syndrome [polyneuropathy, organomegaly, endocrinopathy, M‐protein, and skin changes]). Weight loss, progression of the neuropathy, and an M‐protein level > 1 g/L were independent risk factors for malignancy. Extensive screening is indicated in patients with these features. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1295–1302, 2001