bluuebunny/crossref_metadata_2025 huggingface dataset:
The neurotrophin receptors, trkB and p75, differentially regulate motor axonal regeneration
Authors: Boyd J. G. , Gordon T.
Published: August 2002

Neurotrophic factors that support neuronal survival are implicated in axonal regeneration after injury. Specifically, a strong role for BDNF in motor axonal regeneration has been suggested based on its pattern of expression after injury, as well as the expression of its receptors, trkB and p75. Despite considerable in vitro evidence, which demonstrate specific and distinct physiological responses elicited following trkB and p75 activation, relatively little is known about the function of these receptors in vivo. To investigate the roles of the trkB and p75 receptors in motor axonal regeneration, we have used a tibial (TIB)‐ common peroneal (CP) cross suture paradigm in p75 homozygous (−/−) knockout mice, trkB heterozygous (+/−) knockout mice, as well as in their wild‐type controls. Contralateral intact TIB motoneurons, and axotomized TIB motoneurons that regenerated their axons 10 mm into the CP distal nerve stump were identified by fluorescent retrograde tracers and counted in the T11‐L1 spinal segments. Regeneration was evaluated 2, 3, 4, 6, and 8 weeks after nerve repair. Compared to wild‐type animals, there are significantly fewer intact TIB motoneurons in p75 (−/−), but not trkB (+/−) mice. The number of motoneurons that regenerated their axons was significantly increased in the p75 (−/−) knockout mice, but significantly attenuated in the trkB (+/−) mice compared to wild‐type controls. These results suggest that p75 is important for motoneuronal survival during development, but p75 expression after injury serves to inhibit motor axonal regeneration. In addition, full expression of trkB is critical for complete axonal regeneration to proceed. © 2001 John Wiley & Sons, Inc. J Neurobiol 49: 314–325, 2001
Chronic alterations in serotonin function: Dynamic neurochemical properties in agonistic behavior of the crayfish, Orconectes rusticus
Authors: Panksepp Jules B. , Huber Robert
Published: August 2002

The biogenic amine serotonin [5‐hydroxytryptamine (5‐HT)] has received considerable attention for its role in behavioral phenomena throughout a broad range of invertebrate and vertebrate taxa. Acute 5‐HT infusion decreases the likelihood of crayfish to retreat from dominant opponents. The present study reports the biochemical and behavioral effects resulting from chronic treatment with 5‐HT‐modifying compounds delivered for up to 5 weeks via silastic tube implants. High performance liquid chromatography with electrochemical detection (HPLC‐ED) confirmed that 5,7‐dihydroxytryptamine (5,7‐DHT) effectively reduced 5‐HT in all central nervous system (CNS) areas, except brain, while a concurrent accumulation of the compound was observed in all tissues analyzed. Unexpectedly, two different rates of chronic 5‐HT treatment did not increase levels of the amine in the CNS. Behaviorally, 5,7‐DHT treated crayfish exhibited no significant differences in measures of aggression. Although treatment with 5‐HT did not elevate 5‐HT content in the CNS, infusion at a slow rate caused animals to escalate more quickly while 5‐HT treatment at a faster rate resulted in slower escalation. 5,7‐DHT is commonly used in behavioral pharmacology and the present findings suggest its biochemical properties should be more thoroughly examined. Moreover, the apparent presence of powerful compensatory mechanisms indicates our need to adopt an increasingly dynamic view of the serotonergic bases of behavior like crayfish aggression. © 2002 Wiley Periodicals, Inc. J Neurobiol 50: 276–290, 2002; DOI 10.1002/neu.10035
Stimulation of nitric oxide synthase in cerebral cortex due to elevated partial pressures of oxygen: An oxidative stress response
Authors: Thom Stephen R. , Bhopale Veena , Fisher Donald , Manevich Yefim , Huang Paul L. , Buerk Donald G.
Published: August 2002

The purpose of this investigation was to determine the impact of elevated partial pressures of O2 on the steady state concentration of nitric oxide (•NO) in the cerebral cortex. Rodents with implanted O2‐ and •NO‐specific microelectrodes were exposed to O2 at partial pressures from 0.2 to 2.8 atmospheres absolute (ATA) for up to 45 min. Elevations in •NO concentration occurred with all partial pressures above that of ambient air. In rats exposed to 2.8 ATA O2 the increase was 692 ± 73 nM (S.E., n = 5) over control. Changes were not associated with alterations in concentrations of nitric oxide synthase (NOS) enzymes. Based on studies with knock‐out mice lacking genes for neuronal NOS (nNOS) or endothelial NOS (eNOS), nNOS activity contributed over 90% to total •NO elevation due to hyperoxia. Immunoprecipitation studies indicated that hyperoxia doubles the amount of nNOS associated with the molecular chaperone, heat shock protein 90 (Hsp90). Both •NO elevations and the association between nNOS and Hsp90 were inhibited in rats infused with superoxide dismutase. Elevations of •NO were also inhibited by treatment with the relatively specific nNOS inhibitor, 7 nitroindazole, by the ansamycin antibiotics herbimycin and geldanamycin, by the antioxidant N‐acetylcysteine, by the calcium channel blocker nimodipine, and by the N‐methyl‐D‐aspartate inhibitor, MK 801. Hyperoxia did not alter eNOS association with Hsp90, nor did it modify nNOS or eNOS associations with calmodulin, the magnitude of eNOS tyrosine phosphorylation, or nNOS phosphorylation via calmodulin kinase. Cerebral cortex blood flow, measured by laser Doppler flow probe, increased during hyperoxia and may be causally related to elevations of steady state •NO concentration. We conclude that hyperoxia causes an increase in •NO synthesis as part of a response to oxidative stress. Mechanisms for nNOS activation include augmentation in the association with Hsp90 and intracellular entry of calcium. © 2002 Wiley Periodicals, Inc. J Neurobiol 51: 85–100, 2002
Conditional modification of behavior inDrosophilaby targeted expression of a temperature‐sensitiveshibireallele in defined neurons
Authors: Kitamoto Toshihiro
Published: August 2002

Behavior is a manifestation of temporally and spatially defined neuronal activities. To understand how behavior is controlled by the nervous system, it is important to identify the neuronal substrates responsible for these activities, and to elucidate how they are integrated into a functional circuit. I introduce a novel and general method to conditionally perturb anatomically defined neurons in intactDrosophila. In this method, a temperature‐sensitive allele ofshibire(shits1) is overexpressed in neuronal subsets using theGAL4/UASsystem. Because theshigene product is essential for synaptic vesicle recycling, andshits1is semidominant, a simple temperature shift should lead to fast and reversible effects on synaptic transmission ofshits1expressing neurons. Whenshits1expression was directed to cholinergic neurons, adult flies showed a dramatic response to the restrictive temperature, becoming motionless within 2 min at 30°C. This temperature‐induced paralysis was reversible. After being shifted back to the permissive temperature, they readily regained their activity and started to walk in 1 min. Whenshits1was expressed in photoreceptor cells, adults and larvae exhibited temperature‐dependent blindness. These observations show that theGAL4/UASsystem can be used to expressshits1in a specific subset of neurons to cause temperature‐dependent changes in behavior. Because this method allows perturbation of the neuronal activities rapidly and reversibly in a spatially and temporally restricted manner, it will be useful to study the functional significance of particular neuronal subsets in the behavior of intact animals. © 2001 John Wiley & Sons, Inc. J Neurobiol 47: 81–92, 2001
Visualization of neuropeptide expression, transport, and exocytosis in Drosophila melanogaster
Authors: Rao Sujata , Lang Cynthia , Levitan Edwin S. , Deitcher David L.
Published: August 2002

Neuropeptides affect an extremely diverse set of physiological processes. Neuropeptides are often coreleased with neurotransmitters but, unlike neurotransmitters, the neuropeptide target cells may be distant from the site(s) of secretion. Thus, it is often difficult to measure the amount of neuropeptide release in vivo by electrophysiological methods. Here we establish an in vivo system for studying the developmental expression, processing, transport, and release of neuropeptides. A GFP‐tagged atrial natriuretic factor fusion (preproANF‐EMD) was expressed in the Drosophila nervous system with the panneural promoter, elav. During embryonic development, proANF‐EMD was first seen to accumulate in synaptic regions of the CNS in stage 17 embryos. By the third instar larval stage, highly fluorescent neurons were evident throughout the CNS. In the adult, fluorescence was pronounced in the mushroom bodies, antennal lobe, and the central complex. At the larval neuromuscular junction, proANF‐EMD was concentrated in nerve terminals. We compared the release of proANF‐EMD from synaptic boutons of NMJ 6/7, which contain almost exclusively glutamate‐containing clear vesicles, to those of NMJ 12, which include the peptidergic type III boutons. Upon depolarization, approximately 60% of the tagged neuropeptide was released from NMJs of both muscles in 15 min, as assayed by decreased fluorescence. Although the elav promoter was equally active in the motor neurons that innervate both NMJs 6/7 and 12, NMJ 12 contained 46‐fold more neuropeptide and released much more proANF‐EMD during stimulation than did NMJ 6/7. Our results suggest that peptidergic neurons have an enhanced ability to accumulate and/or release neuropeptides as compared to neurons that primarily release classical neurotransmitters. © 2001 John Wiley & Sons, Inc. J Neurobiol 49: 159–172, 2001
A posteriori error estimation for elliptic eigenproblems
Authors: Neymeyr Klaus
Published: August 2002

An a posteriori error estimator is presented for a subspace implementation of preconditioned inverse iteration, which derives from the well‐known inverse iteration in such a way that the associated system of linear equations is solved approximately by using a preconditioner. The error estimator is integrated in an adaptive multigrid algorithm to compute approximations of a modest number of the smallest eigenvalues together with the eigenfunctions of an elliptic differential operator.

Error estimation is applied both within the actual finite element space (in order to estimate the iteration error) as well as in its hierarchical refinement of higher‐order elements (to estimate the discretization error) which gives rise to a balanced reduction of the iteration error and of the discretization error in the adaptive multigrid algorithm. Copyright © 2002 John Wiley & Sons, Ltd.
Filters in topology optimization
Authors: Bourdin Blaise
Published: August 2002

In this article, a modified (‘filtered’) version of the minimum compliance topology optimization problem is studied. The direct dependence of the material properties on its pointwise density is replaced by a regularization of the density field by the mean of a convolution operator. In this setting it is possible to establish the existence of solutions. Moreover, convergence of an approximation by means of finite elements can be obtained. This is illustrated through some numerical experiments. The ‘filtering’ technique is also shown to cope with two important numerical problems in topology optimization, checkerboards and mesh dependent designs. Copyright © 2001 John Wiley & Sons, Ltd.
A new method for modelling cohesive cracks using finite elements
Authors: Wells G. N. , Sluys L. J.
Published: August 2002

A model which allows the introduction of displacements jumps to conventional finite elements is developed. The path of the discontinuity is completely independent of the mesh structure. Unlike so‐called ‘embedded discontinuity’ models, which are based on incompatible strain modes, there is no restriction on the type of underlying solid finite element that can be used and displacement jumps are continuous across element boundaries. Using finite element shape functions as partitions of unity, the displacement jump across a crack is represented by extra degrees of freedom at existing nodes. To model fracture in quasi‐brittle heterogeneous materials, a cohesive crack model is used. Numerical simulations illustrate the ability of the method to objectively simulate fracture with unstructured meshes. Copyright © 2001 John Wiley & Sons, Ltd.
Parameter identification with weightless regularization
Authors: Furukawa Tomonari
Published: August 2002

Although the regularization increased the popularity of parameter identification due to its capability of deriving a stable solution, the significant problem is that the solution depends upon the regularization parameters chosen. This paper presents a technique for deriving solutions without the use of the parameters and, further, an optimization method, which can work efficiently for problems of concern. Numerical examples show that the technique can efficiently search for appropriate solutions. Copyright © 2001 John Wiley & Sons, Ltd.
The computation of the exponential and logarithmic mappings and their first and second linearizations
Authors: Ortiz M. , Radovitzky R. A. , Repetto E. A.
Published: August 2002

We describe two simple methods for the evaluation of the exponential and logarithmic mappings and their first and second linearizations based on the Taylor expansion and the spectral representation. We also provide guidelines for switching between those representations on the basis of the size of the argument. The first and second linearizations of the exponential and logarithmic mappings provided here are based directly on the exponential formula for the solutions of systems of linear ordinary differential equations. This representation does not require the use of perturbation formulae for eigenvalues and eigenvectors. Our approach leads to workable and straightforward expressions for the first and second linearizations of the exponential and logarithmic mappings regardless of degeneracies in the spectral decomposition of the argument. Copyright © 2001 John Wiley & Sons, Ltd.
Fleet Financial and Radcliffe Explore Paths of Work/Life Integration
Authors: Bailyn Lotte , Rayman Paula , Bengtsen Dale , Carré Françoise , Tierney Mark
Published: August 2002

Many organizations have used the redesign of jobs—work processes, schedules, work loads, task assignments—as a strategy for improving productivity and other measures of bottom‐line effectiveness. Far fewer have recognized that job redesign can be a fundamental, critical strategy for the achievement of work/life balance. Most organizations still conceive of productivity and work/life balance as separate goals to be reached by different paths.

The Radcliffe‐Fleet Work and Life Integration Project directly addresses this split. The Fleet Financial Group, emerging from a period of sweeping internal and external change, saw the need to improve its service and to improve its standing as an employer of choice. The Radcliffe Public Policy Institute was eager to conduct a project to demonstrate the principle that redesign of jobs can further the dual goals of improved service and work/life balance. © 2001 John Wiley & Sons, Inc.
Transition to home care after stroke: Depression, physical health, and adaptive processes in support persons
Authors: King Rosemarie B. , Carlson Carolyn E. , Shade‐Zeldow Yvonne , Bares Kimberly K. , Roth Elliot J. , Heinemann Allen W.
Published: August 2002

A longitudinal design was used to examine adaptation in primary support persons (PSP) of stroke survivors during the transition from hospitalization (T1) to home care (T2). The major purposes of the study were (a) to examine changes in depression, physical health, and contextual and coping factors from hospitalization of the stroke survivor through the first 6–10 weeks of home care; and (b) to identify predictors of depression. Data (N = 136) were collected on depression, physical health, background, survivor illness, and social environmental variables; appraisal of impact; social support resources; and coping skills. Reduction in mean PSP depression was significant at T2, but the change in physical health was not significant. Significant changes occurred in survivor function, family functioning, and three of six coping skills. Hierarchical multiple regression analyses were used to predict depression. T1 variables accounted for 29% of the variance in T1 PSP depression, with gender and appraisal of impact the strongest of seven predictors. T1 depression, T2 health, family functioning, and avoidance coping were the strongest of seven predictors, explaining 50% of the variance in T2 depression. Findings highlight the importance of maintaining caregiver health and preventing depression and identify variables to target for the reduction of PSP depression. © 2001 John Wiley & Sons, Inc. Res Nurs Health 24:307–323, 2001
Enamel hypoplasia in Danish and Lithuanian Late Medieval/Early Modern samples: a possible reflection of child morbidity and mortality patterns
Authors: Palubeckaitė Žydrūnė , Jankauskas Rimantas , Boldsen Jesper
Published: August 2002

Numerous studies and various interpretations of the prevalence of linear enamel hypoplasias (LEH) based on populations living in different cultural and economic conditions are causing some confusion and raising doubts about whether or not such LEH are reliable indicators of life conditions. An analysis of LEH prevalence patterns was performed on the adults of three populations: Tirup—a Danish Medieval rural population of the 12–14th centuries (131 individuals), Subačiaus str. in Vilnius—a Lithuanian Late Medieval urban population of the 16–17th centuries (88 individuals), and the aristocracy—a Lithuanian pooled sample population from several churches of the 15–18th centuries (66 individuals). Statistical testing of the influence of population affinity, sex and age at death was also performed. Since the same investigator scored all the samples, possible inter‐observer error bias was minimized.

In all the populations, LEH formation ages were similar. Statistically significant sex differences were found only in the aristocratic sample (with higher male frequency). It was found that the town population was characterized by the highest frequency of affected individuals, with the highest severity and highest number of stress episodes per individual. A reliable relationship with age at death was found only in the town sample: individuals with more numerous and more marked LEH had shorter life expectancies in adulthood. Different “most vulnerable years” for subsequent life expectancies were noted for different populations. A tentative explanation of these differences could be the pooled effect of differential morbidity and mortality. It seems that the rural population experienced the highest morbidity and nutrition deficiency as well as the highest child mortality whereas, in the urban sample, high morbidity was accompanied by a lower child mortality. Both lower morbidity and mortality seem to be characteristic for the aristocracy. Copyright © 2002 John Wiley & Sons, Ltd.
Social and ritual determinants of whale bone transport at a classic Thule winter site in the Canadian Arctic
Authors: Whitridge Peter
Published: August 2002

Recent research has demonstrated that patterning related to harvesting selectivity and architectural bone utilization persists in the surface distribution of bowhead whale (Balaena mysticetus) bones at classic Thule sites in the Canadian central Arctic, despite scavenging by later non‐whaling Inuit groups. Since skeletal riders with minimal architectural or artifactual utility are associated with carcass portions that were socially and ritually prized ethnographically in North Alaska, this surface record may also preserve spatial structure relating to loci of high status settlement and/or ceremonial activity within sites. Close to 3400 bowhead bones were mapped at the major Thule winter village of Qariaraqyuk, southeast Somerset Island. The results of a principal components analysis of the element distributions are consistent with expectations for special treatment of bowhead flippers, tails, and tongues. These results are supported by excavation data which reveal that flipper and tongue bones were preferentially discarded in the vicinity of wealthy whaling households and a major ceremonial structure. Contrary to the longstanding belief that Thule whale bone assemblages are hopelessly compromised by prehistoric and historic bone transport, these assemblages hold great promise for investigating Thule social and ritual practices. Copyright © 2002 John Wiley & Sons, Ltd.
NLO‐active maleimide copolymers with ­high glass transition temperatures
Authors: Kato Masao , Shiraga Takao , Kimura Tatsumi , Fukuda Takashi , Matsuda Hiro , Nakanishi Hachiro
Published: August 2002

We synthesized some novel rigid NLO‐active maleimide copolymers bearing DR‐1 moieties (PMPD, PHSD and PHND). All copolymers exhibited high Tg's (190∼197 °C), good solubilities for common solvents and excellent film‐forming properties. Dependence of film thickness on the d33 value for the poled copolymer films induced by corona poling was investigated and it was demonstrated that in less than thickness of 0.3 µm decrease of the thickness gives rise to remarkable increase in the d33 value. The poled copolymer films exhibited large d33 values (270 × 10−9 esu (film thickness 0.13 µm) for PMPD, 290 × 10−9 esu (0.12 µm) for PHSD and 350 × 10−9 esu (0.08 µm) for PHND) as well as large r33 values (51.0 pmV−1 for PMPD and 60.4 pmV−1 for PHND) which are significantly large compared to the value of LiNbO3 (31 pmV−1) as a typical EO material. The d33 values of the poled copolymers were kept constant even after standing 1000h at 80 °C, although a small decrease was observed at an initial stage. Further, the d33 values did not change up to ca. 123 °C upon heating at the rate of 10 °C/min in all cases. Copyright © 2002 John Wiley & Sons, Ltd.
Oxidation assisted new reaction of glycerol
Authors: Kimura Hiroshi
Published: August 2002

Catalytic oxidation of tartronic acid (TA) in water over a BiPt/C catalyst generates ketomalonic acid (KM) which polymerizes via ketone‐carbonyl to form the corresponding polyether, poly(ketomalonate) (PKM), preventing the competitive formation of KM‐hydrate available as reagent. Formation of the polyether (I) and of the hydrate (II) constitute the relaxation processes of generated active KM (keto‐form). Polymerization of KM proceeds cationically or anionically depending on pH, which shows that ketone‐carbonyl of KM is a dipole. TA, which can be prepared by catalytic oxidation of glycerol (GLY), functions as a precursor for KM as well as initiators such as proton or TA‐carbanion for cationic and anionic polymerization of KM, respectively. Perchloric acid and zinc chloride are effective promoters for polymerization of KM. The CeBiPt/C is an excellent multi‐functional catalyst which has three functions; (a) oxidation of the two primary hydroxy groups of GLY to form TA; (b) oxidation of the secondary hydroxy group of TA to generate KM; (c) polymerization of generated KM. PKM prepared by anionic polymerization of KM has no hydrogens bonded to the carbon atoms of the polyether chain. Decarboxylation of PKM can be easily performed by adding mineral acid. This shows that PKM is a polymer of carbon dioxide which is bonded to carbon of the polyether chain and is stabilized by sodium ion. Excess oxidation of PKM formed by pure oxygen accelerates complete decarboxylation to form poly(oxymethylene). These observations, assisted by catalytic oxidation, demonstrate new chemistry of GLY as a renewable resource. TA‐carbanion can also be used as an initiator for the anionic polymerization of glyoxylic acid (GOA) in a basic aqueous media to form poly(glyoxylate).

Zinc chloride, a Lewis acid, can be an initiator for cationic polymerization of half‐neutralized GOA in water. GOA, which has been generally used as an ester for polyether synthesis, can be polymerized in water by controlling pH‐dependent hydration equilibrium of GOA to aldehyde‐form. Copolymer of KM and pyruvic acid prepared by anionic copolymerization initiated by TA‐carbanion shows excellent Ca‐sequestrancy as a detergent builder. Polymerization of a substituted ketone, generated by catalytic oxidation of a corresponding precursor, polymerizes via ketone‐carbonyl even in water to form the corresponding polyether. Oxidative polymerization in water of an aliphatic hydroxy compound is a new methodology for the advancement of fine chemistry and functional polymers. Copyright © 2001 John Wiley & Sons, Ltd.
Immunomodulation of experimental colitis: the role of NK1.1 liver lymphocytes and surrogate antigens – bystander effect
Authors: Shlomai Amir , Trop Shivti , Gotsman Israel , Jurim Oded , Diment Judith , Alper Ruslana , Rabbani Elazar , Engelhardt Dean , Ilan Yaron
Published: August 2002

The imbalance between Th1 pro‐inflammatory and Th2 anti‐inflammatory cytokine‐producing cells plays a major role in the pathogenesis of inflammatory bowel disease (IBD). Induction of oral tolerance to colitis‐extracted proteins was previously shown to down‐regulate the anti‐colon immune response, thereby alleviating experimental colitis. Immune bystander effect and liver‐associated lymphocytes expressing the NK1.1 marker (NK1.1+ LAL) have been suggested as being important in tolerance induction. The aims of the present study were to determine whether oral administration of inflammatory and non‐inflammatory colon‐extracted proteins of different species can induce peripheral immune tolerance and alleviate experimental colitis; and to examine the role of NK1.1+ LAL in oral tolerance induction. Colitis was induced in C57/B6 mice by intracolonic instillation of trinitrobenzene sulphonic acid (TNBS). Mice received six oral doses of colonic proteins extracted from TNBS‐colitis colonic wall, or normal colonic wall, from four different species. Standard clinical, macroscopic, and microscopic scores were used for colitis assessment. Serum interferon γ (IFNγ) and interleukin 10 (IL10) levels were measured by ELISA. To evaluate the role of NK1.1+ LAL in maintaining the balance between immunogenic and tolerogenic subsets of cells, their cytotoxicity functions were tested in tolerized and non‐tolerized‐mice. The administration of mouse‐derived colitis‐extracted proteins, or of surrogate proteins extracted from normal mouse colon, or from rat or human inflammatory colons, was found to alleviate experimental colitis. Tolerized mice had less diarrhoea; showed a marked reduction of colonic ulceration, intestinal and peritoneal adhesions, wall thickness, and oedema; and demonstrated a significant improvement of all microscopic parameters for colitis. Induction of tolerance led to an increase in IL10 and a decrease in IFNγ serum levels. NK1.1+ LAL cytotoxicity function increased markedly in tolerized mice. In contrast, mice fed with proteins extracted from normal rat, rabbit, and human colon, or from rabbit inflammatory colon, developed severe colitis, with a marked increase in IFNγ and a decrease in IL10 serum levels, and down‐regulation of NK1.1+ LAL function. This study has shown that oral tolerance can be induced in experimental colitis by means of the feeding of surrogate antigens; this alleviates experimental colitis. NK1.1+ LAL cytotoxicity function is associated with peripheral tolerance induction and may help to maintain the Th1/Th2 immune balance. Copyright © 2001 John Wiley & Sons, Ltd.
Localization of angiotensin‐converting enzyme in the human prostate: pathological expression in benign prostatic hyperplasia
Authors: Nassis Labrini , Frauman Albert G. , Ohishi Mitsuru , Zhuo Jialong , Casley David J. , Johnston Colin I. , Fabiani Maurice E.
Published: August 2002

Benign prostatic hyperplasia (BPH) is the most common hyperplastic disease in man and it is characterized by increased cellular growth (stromal and epithelial hyperplasia) and enhanced local sympathetic tone, both of which are known to be augmented by activation of the renin–angiotensin system (RAS) in other tissues. Angiotensin‐converting enzyme (ACE) is an integral component of the RAS that is responsible for the production of the active peptide angiotensin II from the inactive precursor angiotensin I. The present study was undertaken to map the anatomical localization of ACE protein and messenger ribonucleic acid (mRNA) in the normal human prostate and to establish whether their expression is pathologically altered in BPH. Human prostate samples were obtained at post‐mortem and histologically defined as normal or hyperplastic. ACE protein binding/expression was determined by in vitro autoradiography and immunohistochemistry using the ACE‐specific radioligand [125I]‐MK351A and a mouse anti‐ACE polyclonal antibody, respectively, whereas the spatiotemporal distribution of ACE mRNA was determined by in situ hybridization using 35S‐labelled oligonucleotide probes. ACE protein was localized to the glandular epithelium in the human prostate. ACE binding and immunostaining were increased in BPH compared with normal (non‐hyperplastic) prostate specimens [X‐ray film autoradiography: normal 873±48 dpm/mm2 (n=8) vs. BPH 1631±274 dpm/mm2 (n=6), p<0.05; emulsion autoradiography: normal 3.1±0.5 grains/mm2 (n=6) vs. BPH 32.8±8.6 grains/mm2 (n=5), p<0.01]. ACE mRNA was also localized to glandular epithelial cells in the human prostate with a significant increase in ACE mRNA expression in BPH compared with the normal prostate [normal 11.04±2.03 grains/cell (n=220 cells total) vs. BPH 22.29±1.34 grains/cell (n=198 cells total), p<0.05]. The findings of the present study suggest that ACE is localized to the glandular epithelium of the human prostate and that its expression, at both protein and mRNA level, is aberrantly increased in BPH. These data support the concept that hyperactivity of the local RAS in the prostate may be involved in the pathogenesis of BPH. Copyright © 2001 John Wiley & Sons, Ltd.
Prenatal diagnosis of Pelizaeus‐Merzbacher disease: detection of proteolipid protein gene duplication by quantitative fluorescent multiplex PCR
Authors: Regis Stefano , Filocamo Mirella , Mazzotti Raffaella , Cusano Roberto , Corsolini Fabio , Bonuccelli Gloria , Stroppiano Marina , Gatti Rosanna
Published: August 2002

A prenatal diagnosis of Pelizaeus‐Merzbacher disease (PMD) resulting from proteolipid protein gene (PLP) duplication was performed by a quantitative fluorescent multiplex PCR method. PLP gene copy number was determined in the proband, the pregnant mother, the male fetus and two aunts. Small amounts of genomic DNA extracted from peripheral blood and from chorionic villi were used. The fetus, in common with the proband, was identified as PMD‐affected being a carrier of the PLP gene duplication, inherited from the mother, while the two aunts were non‐carriers. The data obtained were confirmed by segregation analysis of a PLP‐associated dinucleotide‐repeat polymorphism amplified by the same multiplex PCR. Copyright © 2001 John Wiley & Sons, Ltd.
Maternal uniparental heterodisomy for chromosome 2: detection through ‘atypical’ maternal AFP/hCG levels, with an update on a previous case
Authors: Wolstenholme J. , White I. , Sturgiss S. , Carter J. , Plant N. , Goodship J. A.
Published: August 2002

We report a case of maternal uniparental disomy 2, detected through routine screening of placental karyotypes following the finding of ‘atypical’ AFP/hCG levels in the second trimester, with intrauterine growth retardation (IUGR) but otherwise normal outcome at term. Although the child remained small, subsequent early physical and mental development has also been normal. Additionally, we report long‐term follow‐up of an earlier case, again with relatively normal physical and mental development. The significance of atypical AFP/hCG results and the predictive value of prenatal testing for UPD2 in trisomy 2 confined placental mosaicism (CPM) cases are discussed. Copyright © 2001 John Wiley & Sons, Ltd.
Fetal and maternal progenitor cells in co‐culture respond equally to erythropoietin
Authors: Bohmer Ralph M. , Johnson Kirby L. , Bianchi Diana W.
Published: August 2002

To explore potentially selective growth conditions for fetal cells in cultures from the blood of pregnant women, we investigated if fetal and adult erythroid progenitors with different hemoglobin expression programs are differentially responsive to erythropoietin (EPO). Co‐cultures of clonogenic cells from 12‐week fetal and adult peripheral blood were established, and the development of erythropoietic cells was monitored using flow cytometric profiles of correlated cellular contents of fetal and adult hemoglobin (HbF and HbA, respectively). Adult nucleated red cells were classified as F+A−, F+A+ or F−A+. All fetal cells were F+A−. The population of F+A− cells was flow‐sorted and fetal cells were identified by fluorescence in situ hybridization (FISH) using chromosome‐specific probes. Delayed EPO addition revealed that all types of erythroid cells entered the EPO‐dependent phase with similar kinetics, beginning at about Day 4. The data suggest that fetal and adult erythroid stem/progenitor cells have the same initial maturation kinetics in culture independent of their hemoglobin chain expression program. Fetal and adult cells with different hemoglobin profiles also showed similar EPO dose–response curves, determined for different intervals during the first 2 weeks of culture. Thus, the kinetics of entry into the phase of EPO dependence, as well as the sensitivity to EPO at various stages of development, are essentially the same for erythropoietic progenitor cells derived from adult and early fetal blood, which rules out the possibility of using the timing or concentration of EPO for the selective growth of fetal cells from the blood of pregnant women. Copyright © 2001 John Wiley & Sons, Ltd.
Significantly higher number of fetal cells in the maternal circulation of women with pre‐eclampsia
Authors: Jansen Mieke W. J. C. , Korver‐Hakkennes Karin , van Leenen Dik , Visser Willy , in 't Veld Peter A. , de Groot Christianne J. M. , Wladimiroff Juriy W.
Published: August 2002

Although the pathophysiology of pre‐eclampsia is unknown, several studies have indicated that abnormal placentation early in pregnancy might play a key role. It has recently been suggested that this abnormal placentation may result in transfusion of fetal cells (feto‐maternal transfusion) in women with pre‐eclampsia. In the present study, fetal nucleated red blood cells were isolated from 20 women with pre‐eclampsia and 20 controls using a very efficient magnetic activated cell sorting (MACS) protocol. The number of male cells was determined using two‐color fluorescence in situ hybridization (FISH) for X and Y chromosomes. Significantly more XY cells could be detected in women with pre‐eclampsia (0.61±1.2 XY cells/ml blood) compared to women with uncomplicated pregnancies (0.02±0.04 XY cells/ml blood) (Mann–Whitney U‐test, p<0.001). These results suggest that fetal cell trafficking is enhanced in women with pre‐eclampsia, and this finding may contribute to the understanding of the pathophysiology of the disease. Copyright © 2001 John Wiley & Sons, Ltd.
Prenatal interphase FISH diagnosis of PLP1 duplication associated with Pelizaeus–Merzbacher disease
Authors: Inoue Ken , Kanai Makoto , Tanabe Yuzo , Kubota Takeo , Kashork Catherine D. , Wakui Keiko , Fukushima Yoshimitsu , Lupski James R. , Shaffer Lisa G.
Published: August 2002

A submicroscopic genomic duplication in Xq22.2 that contains the entire proteolipid protein 1 gene (PLP1) is responsible for the majority of Pelizaeus–Merzbacher disease (PMD) patients. We previously developed an interphase FISH assay to screen for PLP1 duplications in PMD patients using peripheral blood and lymphoblastoid cell lines. This assay has been utilized as a clinical diagnostic test in our cytogenetics laboratory. To expand usage of the interphase FISH assay to prenatal diagnosis of PLP1 duplications, we examined three PMD families with PLP1 duplications utilizing aminiotic fluid samples. In two families the FISH assay revealed fetuses with PLP1 duplications, whereas the other fetus showed a normal copy number of PLP1. Haplotype analyses, as well as an additional FISH analysis using postnatal blood samples, confirmed the results of the prenatal analyses. Our study demonstrates utility of the interphase FISH assay in the prenatal diagnosis of PLP1 duplications in PMD. Copyright © 2001 John Wiley & Sons, Ltd.
Identification of triploid trophoblast cells in peripheral blood of a woman with a partial hydatidiform molar pregnancy
Authors: van Wijk I. J. , de Hoon A. C. , Griffioen S. , Mulders M. A. M. , Tjoa M. L. , van Vugt J. M. G. , Oudejans C. B. M.
Published: August 2002

In a woman with a partial hydatidiform molar pregnancy with 69,XXY karyotype, the presence of male fetal cells of trophoblastic origin was demonstrated in maternal blood by X/Y‐chromosome specific PCR and by immunostaining combined with FISH on two cell populations isolated from maternal blood. Blood was obtained three weeks prior to the detection of fetal demise, at 13 weeks' gestation. Results were confirmed on formalin‐fixed paraffin‐embedded molar tissue, removed at 16 weeks' gestational age for therapeutic reasons. The results indicate that both plasma and cells from maternal peripheral blood might be useful for non‐invasive prenatal diagnosis of fetal aneuploidies, as described in the current case with a partial molar pregnancy. Copyright © 2001 John Wiley & Sons, Ltd.
Fetal renal anomalies and genetic syndromes
Authors: Wellesley Diana , Howe David T.
Published: August 2002

Renal abnormalities are some of the commonest and most easily detectable anomalies on ultrasound. Many are an isolated finding but the prognosis may be altered considerably by the detection of other anomalies which could indicate a genetic disorder or syndrome. It is often easier to detect presupposed anomalies and the purpose of this article is to introduce and discuss those syndromes that may present with a renal abnormality on ultrasound. Common renal findings are presented with the range of additional anomalies that should be sought and suggested diagnostic tests. It should be remembered that although for many genetic conditions specific mutation analysis is now available, this usually requires pre‒pregnancy investigations. Furthermore, in some cases the definitive diagnosis may not be suspected until post mortem. By this time it may be too late to establish a cell line to confirm the suspicion using laboratory methods. It is therefore important to take tissue samples antenatally where possible, or at delivery, as postnatal samples may have a high culture failure rate. Copyright © 2001 John Wiley & Sons, Ltd.
New technique using galactose‐specific lectin for isolation of fetal cells from maternal blood
Authors: Kitagawa Michihiro , Sugiura Kentaro , Omi Hiroko , Akiyama Yoshiaki , Kanayama Kiyoko , Shinya Masaru , Tanaka Tadao , Yura Hirobumi , Sago Haruhiko
Published: August 2002

To isolate fetal cells from maternal blood, we developed a new method based on galactose‐bearing conjugation. Nucleated red blood cells (NRBCs), which highly express galactose on their surface, were selectively attached to a substrate coated with a galactose‐containing polymer via soybean agglutinin (SBA), a galactose‐specific lectin. Cord blood samples were used to evaluate enrichment efficacy of NRBCs by this method. Blood samples were obtained from 131 pregnant women between 6 and 27 gestational weeks. After preliminary condensation of fetal cells by Ficoll gradient centrifugation, NRBCs were enriched using galactose‐positive selection by adjusting SBA concentration. We isolated one to severalhundred NRBCs (mean±SD, 7.8±8.5) in 2.3 ml of peripheral blood samples from 96% of pregnantwomen. The isolated NRBCs were analyzed by a Y‐chromosome FISH probe in eight cases carrying male fetuses. Y‐signals were detected in all eight cases and more than half of the NRBCs wereoffetal origin. The study demonstrates that our new method using galactose‐specific lectin provides effective enrichment of fetal NRBCs allowing non‐invasive prenatal diagnosis. Copyright © 2002 John Wiley & Sons, Ltd.
Maternal serum levels of total activin‐A in first‐trimester trisomy 21 pregnancies
Authors: Spencer Kevin , Liao Adolfo W , Skentou Hariklea , Ong Charas YT , Nicolaides Kypros H
Published: August 2002

Maternal serum total activin‐A concentration was measured in 45 pregnancies affected by trisomy 21 and 493 control unaffected pregnancies at 10–14 weeks of gestation. In the trisomy 21 pregnancies total activin‐A concentration was significantly higher (1.36 MoM of the unaffected pregnancies) and in 16% of cases the level was above the 95th centile of normal. The log10 SD for the control group and the trisomy 21 group were 0.17 and 0.22, respectively. The median pregnancy associated plasma protein‐A (PAPP‐A) in this trisomy 21 series was 0.49 and for free β‐hCG was 2.05. In the trisomy group there were significant positive associations between total activin‐A and PAPP‐A (0.6071) and free β‐hCG (0.4255). The low median difference and the high overlap in values between trisomic and unaffected pregnancies make total activin‐A of little practical use in first‐trimester screening for trisomy 21. Copyright © 2001 John Wiley & Sons, Ltd.
Prenatal diagnosis of congenital cytomegalovirus infection in 189 pregnancies with known outcome
Authors: Enders Gisela , Bäder Ursula , Lindemann Lisa , Schalasta Gunnar , Daiminger Anja
Published: August 2002

An Erratum has been published for this article in Prenatal Diagnosis 21(7) 2001, 605.

Prenatal diagnosis (PD) of fetal cytomegalovirus (CMV) infection was performed in 242 pregnancies, with known outcome in 189 cases. In 141/189 pregnancies, PD was carried out on account of suspicious maternal CMV serology up to gestational week (WG) 23, and in 48 cases on account of abnormal ultrasonic findings detected between WG 18 and 39. Chorionic villus samples (n=6), amniotic fluid (AF, n=176) and/or fetal blood specimens (n=80) were investigated for detection of virus by cell culture, shell vial assay, PCR and/or CMV‐specific IgM antibodies. Of 189 fetuses correctly evaluated by CMV detection either in fetal tissue following therapeutic abortion/stillbirth (n=24) or in urine of neonates within the first 2 weeks of life (n=33), 57 were congenitally infected. In women with proven or suspected primary infection, the intrauterine transmission rates were 20.6% (7/34) and 24.4% (10/41), respectively. Of the congenitally infected live‐born infants, 57.6% (19/33) had symptoms of varying degree. The overall sensitivity of PD in the serologic and ultrasound risk groups was 89.5% (51/57). A sensitivity of 100% was achieved by combining detection of CMV‐DNA and CMV‐specific IgM in fetal blood or by combined testing of AF and fetal blood for CMV‐DNA or IgM antibodies. There was no instance of intrauterine death following the invasive procedure. The predictive value of PD for fetal infection was 95.7% (132/138) for negative results and 100% (51/51) for positive results. Correct results for congenital CMV infection by testing AF samples can be expected with samples obtained after WG 21 and after a time interval of at least 6 weeks between first diagnosis of maternal infection and PD. In case of negative findings in AF or fetal blood and the absence of ultrasound abnormalities at WG 22–23, fetal infection and neonatal disease could be excluded with high confidence. Positive findings for CMV infection in AF and/or fetal blood in combination with CMV suspicious ultrasound abnormalities predicted a high risk of cytomegalic inclusion disease (CID). Furthermore, detection of specific IgM antibodies in fetal blood was significantly correlated with severe outcome for the fetus or the newborn (p=0.0224). However, normal ultrasound of infected fetuses at WG 22–23 can neither completely exclude an abnormal ultrasound at a later WG and the birth of a severely damaged child nor the birth of neonates which are afflicted by single manifestations at birth or later and of the kind which are not detectable by currently available ultrasonographic techniques. Copyright © 2001 John Wiley & Sons, Ltd.
Genetic testing in maturity onset diabetes of the young (MODY): a new challenge for the diabetic clinic
Authors: Shepherd M. , Sparkes A.C. , Hattersley A.T.
Published: August 2002

The identification of five genes that can cause maturity onset diabetes of the young (MODY) means diagnostic and predictive genetic testing is now possible in 80% of MODY families. It is proposed that these recent classifications of diabetes ‘genetic disorders of beta cell function’ are recognised as separate disorders. Diagnostic genetic tests in those with diabetes will define the subtype, which has specific implications for treatment. In non‐diabetic family members predictive tests can be used to test whether the mutated gene has been inherited, indicating >90% chance of developing diabetes.

This article reviews the genetics of MODY and experiences of genetic testing in diabetes to date and considers what can be learnt from genetic testing in other diseases. Experience from MODY and other conditions suggests that personal perception of the illness and lay beliefs about inheritance are important. Discussion of priorities within genetic counselling and motivation for testing are also crucial when communicating genetic information.

Understanding perceptions of genetic information in diabetes and the implications of genetic testing in MODY is a challenge for the 21st century. This will provide insights into how to communicate effectively about genetic testing in diabetes. Genetic testing will be more widely used in the near future as the technology for testing becomes cheaper and easier and other monogenic subtypes of type 2 diabetes are defined. Copyright © 2001 John Wiley & Sons, Ltd.
Gangrene – but not due to diabetic vascular disease
Authors: Gandhi RA , Ibrahim BA , Campbell IW , Nawroz I
Published: August 2002

A 52 year old diabetic female with obstructive jaundice due to cholangiocarcinoma developed recurrent deep venous thrombosis and venous gangrene (phlegmasia caerulia dolens). Carcinomatosis is the usual underlying cause of this rare form of gangrene and has a high mortality. It is important to remember that diabetic subjects can develop ‘non‐diabetic’ gangrene, and other causes should be considered depending upon the clinical presentation. Copyright © 2002 John Wiley & Sons, Ltd.