bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Experimental Flooding on Litter Dynamics in a Rio Grande Riparian Forest, New Mexico
Authors: Ellis Lisa M. , Molles Manuel C. , Crawford Clifford S.
Published: March 2003

Flow regulation, which has largely eliminated flooding along the Rio Grande in central New Mexico, has substantially changed the riparian ecosystem. We investigated managed flooding as a means of restoring ecosystem function. After collecting baseline data during 1991 and 1992 in two riparian forest sites that had not flooded for about 50 years, we flooded an experimental site for 27–32 days during late spring of 1993, 1994, and 1995, leaving the reference site unflooded. During the final year of the study we compared these sites to two additional sites located within the riverside levee, one of which has been flooding naturally while the second remained largely unflooded. Three years of experimental flooding did not change the total biomass of either woody debris or forest‐floor litter at the experimental flood site. Both woody debris and forest‐floor litter, however, were significantly lower at the natural flood site than at the experimental flood site and two unflooded sites. Leaf and wood decomposition rates increased with flooding. The decay rate for cottonwood logs at the unflooded site (0.010 per year) predicted a half‐life of 69.3 years, while the decay rate of 0.065 per year after 3 years of experimental flooding predicted a half‐life of 10.6 years. This suggests that a decade of annual flooding may be used to restore the organic debris to pre‐regulation levels. Flooding may also have caused an increase in litter production. These results suggest that experimental flooding has initiated a process of restoring ecosystem function within the riparian forest.
Simulated Herbivory and Vegetation Dynamics in Coal Slurry Ponds Reclaimed as Wetlands
Authors: Mathis Marilyn J. , Middleton Beth A.
Published: March 2003

The biodiversity of coal slurry ponds can be inhibited, at least in part, by dense stands of Phragmites australis. In this study, we demonstrate that species richness can be increased in coal slurry ponds if the dominant species (P. australis and Typha latifolia) are removed and that underwater herbivory simulated by cutting will kill emergents. The study was conducted in the greenhouse and the field in both flooded and drawndown conditions. Stems of plants of P. australis and T. latifolia were cut in a greenhouse and the cut plants of both species showed a decline in survivorship (25 and 42% survival, respectively) whereas all uncut plants survived. In a reclaimed coal pond at Pyramid State Park, Illinois, neither P. australis nor T. latifolia survived cutting underwater, but all of the uncut plants survived. Regrowth measured as total biomass of stems was less among flooded versus freely drained plants (0.3 and 2.6 g biomass, respectively). Cut versus uncut plants, combining freely drained and flooded, had less below‐ground biomass (99.4 and 254.4 g, respectively). In the greenhouse study, oxygen levels in rhizomes subsequent to cutting were measured using an oxygen electrode and millivolt meter. Oxygen levels in P. australis were lower in cut versus uncut plants both in flooded (15.0 vs. 16.3% ambient O2, respectively) and freely drained conditions (14.5 vs. 15.0%, ambient O2, respectively). Similar responses to cutting were demonstrated by T. latifolia. In an unreclaimed coal slurry pond with monospecific stands of P. australis, plant species richness increased in cut plots as compared to uncut plots (29 vs. 2 species, respectively) between March and September, 1995. This study demonstrated that species richness can be increased in coal ponds by mechanical cutting and this potentially by herbivory; however, the additional species were mostly exotics.
Effects of Nursery Pre‐Conditioning on Panicum hemitomon and Sagittaria lancifolia Used for Wetland Restoration
Authors: Pezeshki S. R. , Anderson P. H. , DeLaune R. D.
Published: March 2003

A study was conducted to examine nursery protocols for production of planting stocks used in wetland mitigation projects. Two commercial soil mixtures were tested along with waterlogging, fertilization, and combination treatments. Two marsh species, Panicum hemitomon and Sagittaria lancifolia, were subjected to a two‐phase study. During Phase I, watering and fertilization treatments were applied in a 2 × 2 × 2 factorial design with two soils, two watering regimes, and two fertilizer treatments. In Phase II, all plants were subjected to continuous waterlogging (no fertilizer). Soil redox potential was measured, along with plant gas exchange and growth responses. Our data do not support the hypothesis that flood “pre‐conditioning” alone can significantly improve plant growth under subsequent flooding. However, fertilization alone or in combination with flooding appeared to enhance shoot and root production in both species during the subsequent flooding. In contrast, flooding alone produced Panicum plants that appeared to remain somewhat susceptible to subsequent flooding as compared to fertilized plants. Sagittaria plants subjected to fertilizer treatment alone did not produce significantly greater total dry weights compared to their controls. Our data indicate that the growth of planting stocks for wetland mitigation can be improved by fertilization in the nursery.

Key words: fertilizer, flooding, nursery production, wetland mitigation.
Effects of Resource‐Island Soils, Competition, and Inoculation with Azospirillum on Survival and Growth of Pachycereus pringlei, the Giant Cactus of the Sonoran Desert
Authors: Carrillo‐Garcia Ángel , Bashan Yoav , Rivera Ernesto Díaz , Bethlenfalvay Gabor J.
Published: March 2003

Resource‐island soils formed by some plants in arid lands are capable of supporting certain plants that do not normally establish in surrounding areas free of vegetation. We determined growth responses of Pachycereus pringlei (cardon), the giant columnar cactus, whose widespread, finely branched, subsurface root systems stabilize desert soils, to four soils collected from within or outside of resource islands. Traits of cardon grown in soils from mature (MM) or young (YM) Prosopis articulata (mesquite), mature Olnea testosa (ironwood, MI), or bare areas (BA) were compared, to determine differences between the effects of soils due to the identity or the stage of development of nurse plants. The levels of soil N, P, and C contents were in the order MM> > YM > MI BA. The BA soil had the coarsest and MM soil the finest texture. Cardon was also grown in pot cultures inoculated with the plant‐growth‐promoting bacterium Azospirillum brasilense, or in association with a competing grass, Sorghum bicolor (sorghum). Competition did not affect survival rates of cardon in any of the soils after six months of growth, but decreased biomass accumulation by up to 90% in the best (MM) soil. Inoculation of cardon seeds with A. brasilense did not affect survival but resulted in significantly better root and shoot growth, and this effect increased linearly as soil nutrients declined. In the best soil (MM), A. brasilense had no effect on cardon growth, but in the poorest soil (BA) shoot dry mass was almost 60% and root length over 100% greater as a result of inoculation, with responses in the other two soils intermediate. This effect did not appear to be owing to N2 fixation, as nitrogenase activity (acetylene reduction) was not detected in any of the treatments. Soil formation by selected nurse trees in arid areas is an important factor in plant establishment and growth, and the present results indicate that these processes can be impeded or facilitated by the introduction of competing or beneficial organisms. The use of beneficial microorganisms associated with roots may accelerate the restoration of disturbed areas.

Key words: Azospirillum, desert soils, nitrogen fixation, nurse plant, Pachycereus pringlei, plant survival, resource‐island.
The Use of Mixtures of Sulfur and Bracken Litter to Reduce pH of Former Arable Soils and Control Ruderal Species
Authors: Owen K. M. , Marrs R. H.
Published: March 2003

High soil pH has been highlighted as a constraint to the restoration of heathland on ex‐arable land. Previous studies at the Minsmere Reserve of the Royal Society for the Protection of Birds (RSPB) in England have shown that it is possible to acidify ex‐arable soils using elemental sulfur and bracken litter, although sulfur (S) is more effective. Current recommendations suggest that 4 tS/ha need to be applied to reduce soil pH below pH 4, control vigorous ruderal species, and create conditions suitable for Calluna vulgaris (heather) establishment. However, S is relatively expensive, and as bracken litter is moderately abundant within the reserve, it made economic sense to evaluate the potential for mixing S with bracken to see if adequate pH reductions could be achieved at lower S rates. Accordingly an experiment was designed to test the effects of combining S (0–8 t S/ha) and bracken litter (0–10 cm depth layers) on (1) soil pH, (2) cover of ruderal species, and (3) the developing plant community. Significant interactions were detected, especially in the period immediately after application. Where bracken litter was applied the soil pH fell immediately; in contrast, S took at least six months to start reducing pH. Where mixtures were applied there was a synergistic effect, which produced a lower pH than the S or bracken litter applied alone. These effects were most marked at low S application rates, between 0.5–4 t S/ha. The effects of the bracken litter addition also reduced the growth of ruderal species in the period immediately after application, probably through a combination of acidification and physical smothering. There is, therefore, a clear potential to acidify ex‐arable soils using combinations of S and bracken litter in schemes designed to restore Calluna heathland.
Effects of Grazing on Restoration of Southern Mixed Prairie Soils
Authors: Fuhlendorf Samuel D. , Zhang Hailin , Tunnell Tim. R. , Engle David M. , Cross Anne Fernald
Published: March 2003

A comparative analysis of soils and vegetation from cultivated areas reseeded to native grasses and native prairies that have not been cultivated was conducted to evaluate restoration of southern mixed prairie of the Great Plains over the past 30 to 50 years. Restored sites were within large tracts of native prairie and part of long‐term grazing intensity treatments (heavy, moderate, and ungrazed), allowing evaluation of the effects of grazing intensity on prairie restoration. Our objective was to evaluate restored and native sites subjected to heavy and moderate grazing regimes to determine if soil nutrients from reseeded cultivated land recovered after 30 years of management similar to the surrounding prairie and to identify the interactive influence of different levels of grazing and history of cultivation on plant functional group composition and soils in mixed prairies. For this mixed prairie, soil nitrogen and soil carbon on previously cultivated sites was 30 to 40% lower than in uncultivated native prairies, indicating that soils from restored sites have not recovered over the past 30 to 50 years. In addition, it appears that grazing alters the extent of recovery of these grassland soils as indicated by the significant interaction between grazing intensity and cultivation history for soil nitrogen and soil carbon. Management of livestock grazing is likely a critical factor in determining the potential restoration of mixed prairies. Heavy grazing on restored prairies reduces the rate of soil nutrient and organic matter accumulation. These effects are largely due to changes in composition (reduced tallgrasses), reduced litter accumulation, and high cover of bare ground in heavily grazed restored prairies. However, it is evident from this study that regardless of grazing intensity, restoration of native prairie soils requires many decades and possibly external inputs to adequately restore organic matter, soil carbon, and soil nitrogen.
Contrasting Functional Performance of Juvenile Salmon Habitat in Recovering Wetlands of the Salmon River Estuary, Oregon, U.S.A.
Authors: Gray Ayesha , Simenstad Charles A. , Bottom Daniel L. , Cornwell Trevan J.
Published: March 2003

For an estuarine restoration project to be successful it must reverse anthropogenic effects and restore lost ecosystem functions. Restoration projects that aim to rehabilitate endangered species populations make project success even more important, because if misjudged damage to already weakened populations may result. Determining project success depends on our ability to assess the functional state or “performance” and the trajectory of ecosystem development. Mature system structure is often the desired “end point” of restoration and is assumed to provide maximum benefit for target species; however, few studies have measured linkages between structure and function and possible benefits available from early recovery stages. The Salmon River estuary, Oregon, U.S.A., offers a unique opportunity to simultaneously evaluate several estuarine restoration projects and the response of the marsh community while making comparisons with a concurring undiked portion of the estuary. Dikes installed in three locations in the estuary during the early 1960s were removed in 1978, 1987, and 1996, creating a “space‐for‐time substitution” chronosequence. Analysis of the marsh community responses enables us to use the development state of the three recovering marshes to determine a trajectory of estuarine recovery over 23 years and to make comparisons with a reference marsh. We assessed the rate and pattern of juvenile salmon habitat development in terms of fish density, available prey resources, and diet composition of wild juvenile Oncorhynchus tshawytscha (chinook salmon). Results from the outmigration of 1998 and 1999 show differences in fish densities, prey resources, and diet composition among the four sites. Peaks in chinook salmon densities were greatest in the reference site in 1998 and in the youngest (1996) site in 1999. The 1996 marsh had higher densities of chironomids (insects; average 864/m2) and lower densities of amphipods (crustaceans; average 8/m3) when compared with the other sites. Fauna differences were reflected in the diets of juvenile chinook with those occupying the 1978 and 1996 marshes based on insects (especially chironomids), whereas those from the 1987 and reference marshes were based on crustaceans (especially amphipods). Tracking the development of recovering emergent marsh ecosystems in the Salmon River estuary reveals significant fish and invertebrate response in the first 2 to 3 years after marsh restoration. This pulse of productivity in newly restored systems is part of the trajectory of development and indicates some level of early functionality and the efficacy of restoring estuarine marshes for juvenile salmon habitat. However, to truly know the benefits consumers experience in recovering systems requires further analysis that we will present in forthcoming publications.
Avian Response to Bottomland Hardwood Reforestation: The First 10 Years
Authors: Twedt Daniel J. , Wilson R. Randy , Henne‐Kerr Jackie L. , Grosshuesch David A.
Published: March 2003

Bottomland hardwood forests were planted on agricultural fields in Mississippi and Louisiana predominantly using either Quercus species (oaks) or Populus deltoides (eastern cottonwood). We assessed avian colonization of these reforested sites between 2 and 10 years after planting. Rapid vertical growth of cottonwoods (circa 2–3 m/year) resulted in sites with forest structure that supported greater species richness of breeding birds, increased Shannon diversity indices, and supported greater territory densities than on sites planted with slower‐growing oak species. Grassland birds (Spiza americana[Dickcissel] and Sturnella magna[Eastern Meadowlark]) were indicative of species breeding on oak‐dominated reforestation no more than 10 years old. Agelaius phoeniceus (Red‐winged Blackbird) and Colinus virginianus (Northern Bobwhite) characterized cottonwood reforestation no more than 4 years old, whereas 14 species of shrub‐scrub birds (e.g., Passerina cyanea[Indigo Bunting]) and early‐successional forest birds (e.g., Vireo gilvus[Warbling vireo]) typified cottonwood reforestation 5 to 9 years after planting. Rates of daily nest survival did not differ between reforestation strategies. Nest parasitism increased markedly in older cottonwood stands but was overwhelmed by predation as a cause of nest failure. Based on Partners in Flight prioritization scores and territory densities, the value of cottonwood reforestation for avian conservation was significantly greater than that of oak reforestation during their first 10 years. Because of benefits conferred on breeding birds, we recommend reforestation of bottomland hardwoods should include a high proportion of fast‐growing early successional species such as cottonwood.
Smoke, Mulch, and Seed Broadcasting Effects on Woodland Restoration in Western Australia
Authors: Rokich Deanna P. , Dixon Kingsley W. , Sivasithamparam K. , Meney Kathy A.
Published: March 2003

Smoke, canopy‐derived mulch, and broadcast seeds were used to maximize the establishment of Banksia woodland species in sand quarries in Western Australia. Smoke, particularly aerosol smoke, had a positive effect on total seedling recruitment. Pre‐mined (woodland) sites showed a 42‐fold increase in total germinants and a 3‐fold increase in the number of species with aerosol smoke application. Post‐mined (restored) sites showed only a 3.6‐fold increase in total germinants and a 1.4‐fold increase in the number of species. Two water‐based smoke chemicals, DC10 (pH 4.5) and SC63 (pH 2.5), increased seedling recruitment at both sites but were not as effective in stimulating recruitment as aerosol smoke. Neither of the chemicals were effective in significantly increasing species richness. Application of aerosol smoke directly to seeds as a pretreatment before broadcasting had no effect on seedling recruitment. Broadcasting of seeds onto restoration sites significantly increased seedling abundance and richness. Application of a single layer of mulch from the canopy vegetation after seed broadcasting gave optimum seedling recruitment. Two layers of mulch significantly reduced recruitment, as did applying mulch before seed broadcasting. For broad‐scale restoration, the application of smoke on newly restored sites would be more effectively achieved using smoke water sprayed over the soil surface. Species that do not recruit from replaced topsoil could be effectively recovered from broadcast seed rather than from mulch.
Neuroprotective Interactions In Rats Between Paclitaxel And Cisplatin
Authors: McKeage M.J. , Haddad G.G. , Ding L. , Galettis P. , Screnci D. , Zhuang L. , Baguley B.C.
Published: March 2003

Paclitaxel and cisplatin are associated with dose‐limiting neurotoxicity that may result from their differing effects on microtubule stability in peripheral nerves. We hypothesized that such different actions of paclitaxel and cisplatin could be exploited to minimize their neurotoxicity by giving them in combination. Paclitaxel (9–18 micromol/kg/week or 7.7–15.4 mg/kg/week) and cisplatin (5–10 micromol/kg/week or 1.5–3 mg/kg/week) were given alone and in combination to female Wistar rats. Treatment was given once per week for a total of 7–10 weeks. Paclitaxel and cisplatin were given 24 h apart when they were given in combination. Changes in sensory nerve conduction velocity (SNCV) and dorsal root ganglia (DRG) morphology were measured. The nature of their interaction was analyzed using an isobologram. Their antitumor activity alone or in combination was also determined in C57B1/6 mice bearing colon 38 tumors. Reductions in SNCV occurred with paclitaxel alone (P = 0.009), cisplatin alone (P = 0.012), and cisplatin given 24 h before paclitaxel (P < 0.0001). In contrast, there was no significant change in SNCV with paclitaxel given 24 h before cisplatin (P = 0.11). An isobologram showed that the SNCV effects of the drug combinations were less than additive or antagonistic. Cisplatin‐induced morphometric changes in DRG neurons were less marked when cisplatin was given with paclitaxel (P = 0.004). Concentrations of platinum in dorsal root ganglia, sural nerves, and sciatic nerves were not altered by giving paclitaxel before cisplatin. Tumor growth delays (TGD) were greater after treatment with paclitaxel (23.4 mu mol/kg or 20 mg/kg) given 24 h before cisplatin (23.3 micromol/kg or 7 mg/kg) (TGD = 7.5 days) than after paclitaxel (23.4 micromol/kg or 20 mg/kg) (TGD = 2.0 days) or cisplatin (23.3 micromol/kg or 7 mg/kg) (TGD = 3.5 days) alone. Paclitaxel and cisplatin antagonized each other's neurotoxicity in Wistar rats. Combining cytotoxic agents with opposing effects on peripheral nerves has potential for minimizing neurotoxicity in patients.
Molecular Modeling Of The Aldose Reductase‐Inhibitor Complex Based On The X‐Ray Crystal Structure And Studies With Single‐Site‐ Directed Mutants
Authors: Singh S.B. , Malamas M.S. , Hohman T.C. , Nilakantan R. , Carper D.A. , Kitchen D.
Published: March 2003

Aldose reductase (AR) has been implicated in the etiology of the secondary complications of diabetes. This enzyme catalyzes the reduction of glucose to sorbitol using nicotinamide adenine dinucleotide phosphate as an essential cofactor. AR has been localized at the sites of tissue damage, and inhibitors of this enzyme prevent the development of neuropathy, nephropathy, retinopathy, and cataract formation in animal models of diabetes. The crystal structure of AR complexed with zopolrestat, a potent inhibitor of AR, has been described. (1) We have generated a model of the AR‐inhibitor complex based on the reported C alpha coordinates of the protein and results of a structure‐activity relationship study using four structurally distinct classes of inhibitors, recombinant human AR, and four single‐site‐directed mutants of this enzyme. The effects of the site‐directed mutations on residues within the active site of the enzyme were evaluated by average interaction energy calculations and by calculations of carbon atom surface area changes. These values correlated well with the IC50 values for zopolrestat with the wildtype and mutant enzymes, validating the model. On the basis of the zopolrestat‐binding model, we have proposed binding models for 10 other AR inhibitors. Our models have enabled us to gain a qualitative understanding of the binding domains of the enzyme and how different inhibitors impact the size and shape of the binding site.
Ambulatory Blood Pressure, Microalbuminuria, And Autonomic Neuropathy In Adolescents With Type 1 Diabetes
Authors: Lafferty A.R. , Werther G.A. , Clarke C.F.
Published: March 2003

OBJECTIVE—To examine the relationship between 24‐h blood pressure (BP) measurements, urinary albumin excretion rates, and autonomic neuropathy (AN) in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS—A total of 31 patients with microalbuminuria (MA), 20 patients with intermittent MA (I‐MA) and 11 patients with persistent MA (P‐MA) were identified from the diabetes clinics at two major Australian tertiary care pediatric hospitals. Two control groups were used, one consisted of 19 age‐, sex‐, and diabetes duration‐matched adolescents with normoalbuminuria (NA), and the other consisted of 46 age and sex‐matched nondiabetic control subjects. A medical history and physical examination were followed by a series of noninvasive tests of cardiovascular and pupillary autonomic function and then by 24‐h ambulatory blood pressure monitoring (ABPM). RESULTS—ABPM showed an incremental increase in all BP parameters from nondiabetic control subjects through subjects with NA. A parallel incremental increase in diurnal and nocturnal ambulatory heart rates was also evident. Subjects with MA had significantly reduced pupillary adaptation to darkness compared with nondiabetic subjects and subjects with NA. The above results paralleled an incremental increase in HbA(1c) levels in adolescents with type 1 diabetes from subjects with NA to subjects with P‐MA. CONCLUSIONS—Higher 24‐h BP values and evidence of subclinical signs of AN are present before P‐MA develops and may have important implications for timing the introduction of treatments designed to prevent or retard the microvascular complications of type 1 diabetes in adolescents.
Expression Of Rat Insulin‐Like Growth Factor Binding Protein‐6 In The Brain, Spinal Cord, And Sensory Ganglia
Authors: Naeve G.S. , Vana A.M. , Eggold J.R. , Verge G. , Ling N. , Foster A.C.
Published: March 2003

Insulin‐like growth factors (IGFs) are important trophic factors during development as well as in the adult or damaged nervous system. Their trophic actions are modulated by interactions with six distinct IGF binding proteins. The mRNA expression profiles of binding proteins 2, 4 and 5 in the normal developing and adult CNS are well characterized and are shown to have distinctive, non‐overlapping distributions. The IGF binding protein‐6 (BP6) is also expressed in the CNS, however, details regarding its mRNA expression distribution in the developing and adult nervous system is limited. BP6 has the unique property of preferentially binding the IGF‐II ligand. Coupled with the fact that this ligand is the most abundantly expressed IGF in the adult CNS, this suggests that the IGF‐II/BP6 complex has a unique role in modulating IGF‐II function in the adult brain. In this report the anatomical distribution of BP6 messenger RNA in the developing and adult rat nervous system is presented. In the embryonic animal the CNS expression is tightly restricted to trigeminal ganglia and, relative to the rest of the embryo, this structure has the highest expression. The expression in the forebrain and cerebellum does not occur until after postnatal day 21 and then is primarily associated with GABAergic interneurons, The highest levels of expression in the adult animal are in the hindbrain, spinal cord, cranial ganglia, and dorsal root ganglia. These nuclei in the hindbrain and periphery that express BP6 are all associated with the coordination of sensorimotor function in the cerebellum, which indicates an important role for the BP6/IGF‐II complex in the function and maintenance of these systems.
Circulating Igf‐I And Its Protective Role In The Pathogenesis Of Diabetic Angiopathy
Authors: Janssen J.A.M.J.L. , Lamberts S.W.J.
Published: March 2003

Poor glycaemic control in type 1 diabetes is associated with elevated serum IGFBP‐1 levels and reduced rather than elevated serum IGF‐I levels. Increasing age is accompanied by a further decrease in serum IGF‐I levels as well as an increase in IGFBP‐1 levels in adult diabetic type 1 and type 2 subjects. This is especially observed in diabetic type 1 subjects with manifest microvascular complications. IGFBP‐1 has been proposed as one of the IGF‐I inhibitors in the serum of diabetics. Lowered IGF‐I and increased IGFBP‐1 levels in the blood may thus result in decreased IGF‐I bioavailability at the tissue level. We hypothesize that the premature and progressive decline in serum IGF‐I bioactivity during aging in diabetics ultimately results in insufficient protective effects by IGF‐I in the kidneys, eyes and neurones, and thus the progression of diabetic microvascular complications. If this hypothesis is proven to be right, treatment of diabetic patients with IGF‐I (eventually complexed to IGFBPs) as an adjunct to insulin might prevent and not worsen the development of diabetic microvascular complications.
Charcot‐Marie‐Tooth Neuropathy Type 2 And P0 Point Mutations: Two Novel Amino Acid Substitutions (ASP61GLY, TYR119CYS) and a Possible “Hotspot” on THR124MET
Authors: Senderek J. , Hermanns B. , Lehmann U. , Bergmann C. , Marx G. , Kabus C. , Timmerman V. , Stoltenburg‐Didinger G. , Schroder J.M.
Published: March 2003

Mutations in the gene for the major protein component of peripheral nerve myelin, myelin protein zero (MPZ, PO), cause hereditary disorders of Schwann cell myelin such as Charcot‐Marie‐Tooth neuropathy type 1B (CMT1B), Dejerine‐Sottas syndrome (DSS), and congenital hypomyelinating neuropathy (CHN). More recently, PO mutations were identified in the axonal type of CMT neuropathy, CMT2, which is different from the demyelinating variants with respect to electroneurography and nerve pathology. We screened 49 patients with a clinical and histopathological diagnosis of CMT2 for mutations in the PO gene. Three heterozygous single nucleotide changes were detected: two novel missense mutations, Asp61Gly and Tyr119Cys, and the known Thr124Met substitution, that has already been reported in several CMT patients from different European countries. Haplotype analysis for the PO locus proved that our patients with the 124Met allele were not related to a cohort of patients with the same mutation, all of Belgian descent and all found to share a common ancestor (7). Our data suggest that PO mutations account for a detectable proportion of CMT2 cases with virtually every patient harbouring a different mutation but recurrence of the Thr124Met amino acid substitution. The high frequency of this peculiar genotype in the European CMT population is presumably not only due to a founder effect but Thr124Met might constitute a mutation hotspot in the PO gene as well.
Patterns Of Quantitative Sensation Testing Of Hypoesthesia And Hyperalgesia Are Predictive Of Diabetic Polyneuropathy—a Study Of Three Cohorts
Authors: Dyck P.J. , Dyck P.J.B. , Velosa J.A. , Larson T.S. , O'brien P.C.
Published: March 2003

OBJECTIVE—To test quantitative sensation testing (QST) patterns of hypoesthesia and hyperalgesia as indicators of diabetic polyneuropathy (DPN) and its severity. RESEARCH DESIGN AND METHODS—We used Computer‐Assisted Sensory Examination IV characterized the QST results of the foot of each patient in three diabetic cohorts (similar to 1,500 patients) as hyperesthetic (less than or equal to 2.5th percentile), low‐normal (2.5th–50th percentiles), high‐normal (50th–97.5th percentiles), or hypoesthetic (greater than or equal to 97.5th percentile), and tested associations with symptoms, impairments, and test abnormalities. RESULTS—Overall neuropathic impairment was most severe in the pancreas‐renal transplant and nerve growth factor cohorts, but it was much less severe in the population‐based Rochester Diabetic Neuropathy Study (RDNS) cohort. The frequency distribution of sensory abnormalities mirrored this difference. When the QST spectra of diabetic cohorts were compared with those of the control subject cohort for vibration and cooling sensations, the only abnormality observed was hypoesthesia, which was expressed as an increased number of subjects with values at or above the 97.5th percentile or by an increased percentage of cases with high‐normal values. Symptoms and impairments of DPN were significantly more frequent in the subjects with Values at or above the 97.5th percentile than in the subjects whose values were between the 50th and 97.5th percentiles. For heat pain (HP) sensation thresholds (intermediate pain severity [HP:5], pain threshold [HP:0.5], and pain‐stimulus response slope [HP:5‐0.5]), an increased frequency of both hypoalgesia and hyperalgesia was observed (especially in the RDNS cohort). Steeper pain‐stimulus response slopes were significantly associated with sensory symptoms, including severity of pain. CONCLUSIONS—1) Decreased vibratory sensation (hypoesthesia) appears to be characteristic of mild DPN, whereas pan‐modality hypoesthesia is characteristic of severe DPN. 2) A shift of vibratory and cold detection thresholds and also of attributes of nerve conduction and a measure of autonomic dysfunction from low‐normal (2.5th–50th percentiles) to high‐normal (50th–37.5th percentiles) appears to precede overt expression of DPN and to thereby provide evidence of subclinical abnormality. 3) Heat stimulus‐induced hyperesthesia (low thresholds) occurs especially in mild DPN, and, because it correlates with DPN symptoms and impairments, it must be attributed to hyperalgesia rather than to supersensitivity. Therefore, hypoalgesia or hyperalgesia may be an indicator of early DPN.
Screening For Mutations In The Peripheral Myelin Genes PMP22, MPZ AND CX32 (GJB1) in Russian Charcot‐Marie‐Tooth Neuropathy Patients
Authors: Mersiyanova I.V. , Ismailov S.M. , Polyakov A.V. , Dadali E.L. , Fedotov V.P. , Nelis E. , Lofgren A. , Timmerman V. , Van Broeckhoven C. , Evgrafov O.V.
Published: March 2003

Charcot‐Marie‐Tooth disease (CMT) and related inherited peripheral neuropathies, including Dejerine‐Sottas syndrome, congenital hypomyelination, and hereditary neuropathy with liability to pressure palsies (HNPP), are caused by mutations in three myelin genes: PMP22, MPZ and Cx32 (GJB1). The most common mutations are the 1.5 Mb CMTIA tandem duplication on chromosome 17p11.2‐p12 in CMT1 patients and the reciprocal 1.5 Mb deletion in HNPP patients. We performed a mutation screening in 174 unrelated CMT patients and three HNPP families of Russian origin. The unrelated CMT patients included 108 clinically and electrophysiologically diagnosed CMT1 cases, 32 CMT2 cases, and 34 cases with unspecified CMT. Fifty‐nine CMT1A duplications were found, of which 58 belonged to the CMT1 patient group. We found twelve distinct mutations in Cx32, six mutations in MPZ, and two mutations in PMP22. Of these respectively, eight, five, and two lead to a CMT1 phenotype. Eight mutations (Cx32: Ile20Asn/ Gly21Ser, Met34Lys, Leu90Val, and Phe193Leu, MPZ: Asp134Gly, Lys138Asn, and Thr139Asn, PMP22: ValSer25‐26del) were not reported previously. Phenotype‐genotype correlations were based on nerve conduction velocity studies and mutation type.
Effects Of Topically Applied Capsaicin Cream On Neurogenic Inflammation And Thermal Sensitivity In Rats
Authors: Yoshimura M. , Yonehara N. , Ito T. , Kawai Y. , Tamura T.
Published: March 2003

The effects of capsaicin cream on neurogenic inflammation and thermal nociceptive threshold were investigated in rats. Firstly, for topical application of capsaicin cream to hind paw, we shaped boots from dental cement to prevent the animals from licking off the drug. Capsaicin cream (1%) led to significant increases in the amounts of Evans blue and substance P (SP) released into the perfusate, and the former response was significantly suppressed by pretreatment with RP67580, an NK1‐receptor antagonist, but not by treatment with an NK2‐receptor antagonist. Subsequent electrical stimulation of the sciatic nerve resulted in a significant reduction in Evans blue and SP extravasation 24 h after topical application of capsaicin cream. On the other hand, when capsaicin cream was repeatedly applied to both hind paws once a day, withdrawal latency for noxious heat stimulation decreased after 24 h, and this thermal hyperalgesia was reversed 3 days later. These results suggest that capsaicin cream initially affects neurogenic inflammation mechanisms and then blocks the pain transmission mechanism.
Antibodies To Neuroblastoma Cells In Rheumatoid Arthritis: A Potential Marker For Neuropathy
Authors: Salih A.M. , Nixon N.B. , Dawes P.T. , Mattey D.L.
Published: March 2003

OBJECTIVE: To investigate the prevalence of antibodies to neuroblastoma cells in patients with rheumatoid arthritis (RA) complicated by peripheral neuropathy (PN), and to determine whether there is any relationship of these antibodies with the severity of neuropathy. METHODS: The study was carried out on 28 patients with RA complicated by PN, 29 RA patients without PN mid 28 healthy volunteers (HV). A cell‐based ELISA method was used to test sera for the presence of IgG and IgM anti‐neuroblastoma cell antibodies. Localisation and characterisation of neuroblastoma antigens recognised by patient's sera was carried out by immunofluorescent microscopy and Western blotting. RESULTS: Elevated levels of IgG anti‐neuroblastoma cell antibodies were found in 10 (36%) neuropathic patients and in 1 (3%) RA control (chi2 = 9.53, P = 0.002), while significant levels of IgM anti‐neuroblastoma cell antibodies were demonstrated in 10 (36%) neuropathic patients and in 2 (7%) RA controls (chi2 = 7.12, P = 0.008). Overall, the levels of antibodies in healthy volunteers were significantly lower than in RA controls and patients with PN. No significant relationship was found between the level of anti‐neuroblastoma cell antibodies and severity of RA or neuropathy. Immunofluorescence staining of neuroblastoma cells with sera from 18 neuropathic patients demonstrated cytoplasmic and/or nuclear‐patterns. Western blotting demonstrated reactivity with a heterogeneous group of neuroblastoma antigens. Little or no reactivity was seen with RA control or HV sera. CONCLUSION: Antibodies against neuroblastoma cells are more prevalent in RA patients with peripheral neuropathy than in RA patients without peripheral nerve involvement. Such antibodies may be useful diagnostic markers for peripheral neuropathy in RA.
Heavy Snorer's Disease: A Progressive Local Neuropathy
Authors: Friberg D.
Published: March 2003

“Heavy snorer's disease” is defined as progression from heavy snoring to obstructive sleep apnoea syndrome (OSAS). Apart from significant weight gain, the aetiology underlying progression to a collapse of the upper airways during inspiration and sleep remains unclear. Previous studies have shown that nocturnal respiratory disturbances became worse, even in some OSAS patients who did not gain weight. The patency of the upper airways depends on the balance between the negative intrapharyngeal pressure developed during inspiration and its counteraction by dilating muscles. The reflexogenic dilation is probably mediated by afferent nerve endings in the pharyngeal mucosa. Chronic vibration of a tissue may cause neuronal damage. Therefore, the hypothesis that snoring per se might cause progressive pharyngeal nerve lesion has been tested in a series of studies from the Karolinska institute, Stockholm, which, along with other studies, will be reviewed here. In these studies it was found that a majority of patients with heavy snoring and different degrees of respiratory disturbance had signs of pharyngeal afferent and efferent (motor) nerve lesions. These lesions may cause the collapse of upper airways in OSAS. Since it is not known which “heavy snorer” will develop OSAS, early effective prevention and/or treatment of snoring is called for.
The Risk Factors For Diabetic Complications
Authors: Dyck Pj
Published: March 2003

The major late complications of diabetes mellitus can be classified into those attributable to atherosclerosis (heart attacks, stroke, and peripheral vascular disease) and to microvascular disease (diabetic polyneuropathy [DPN], retinopathy, and nephropathy). The risk factors for diabetic polyneuropathy had not previously been adequately assessed by: 1) assessing representative population‐based cohorts; 2) assessing DPN comprehensively and quantitatively; 3) expressing nerve tests as a percentile and normal deviate value correcting for anthropometric characteristics as based on study of a randomly selected normal subject cohort from which neurologic disease had been excluded; 4) assessing risk factors serially over time; and 5) performing multivariate analysis of risk factors. For DPN we have found that the risk factors are: 1) markers of diabetic microvessel disease (diabetic retinopathy, 24‐hour proteinuria, or 24‐hour microalbuminuria); 2) chronic hyperglycemic exposure; and 3) type of DM. Excluding markers of microvessel disease and type of DM we found that the highest correlation coefficients were obtained by glycated hemoglobin (GH) × duration of DM 1/2 × 18/age of onset DM (lowest score = 1) × total plasma antioxidant activity. Similarly, major determinants for diabetic retinopathy and nephropathy also are GH × duration of DM. These results provide strong supportive evidence that the product of chronic hyperglycemic (especially GH) exposure × duration of DM are the main determinants of the diabetic complications of retinopathy, nephropathy, and neuropathy.
Acute Inflammatory Responses In Wallerian Degeneration In STZ‐Induced Diabetic Rats
Authors: Kamijo M , Iwama Y , Hasegawa K , Baba M.
Published: March 2003

Recently, chronic inflammatory cell responses including the upregulation of soluble adhesion molecules have been focused as a pathogenesis of chronic diabetic complications. However the response associated with acute Wallerian degeneration (WD) in diabetic nerve has not been evaluated. In this study, we investigated the pathological profiles of acute inflammation and its role in the development of WD in axotomized sciatic nerves in both control and streptozotocin induced diabetic rats. Activated macrophages were observed in the epineurial and the endoneurial area in both control (C) and diabetes (D) at 3 and 14 days after axotomy. However, the density of macrophages in diabetes was significantly reduced in the endoneurial area (3 days: C 74 ± 8/mm2 vs. D 28 ± 12/mm2, Mean ± SD, P < 0.01). CD8+ lymphocytes were rich in migration on the epineurial area at 3 days after axotomy in control. In contrast, density of CD8+ cell was significantly reduced in diabetes (C 132 ± 19/mm2 vs. D 75 ± 8/mm2, P < 0.005). At 14 days after axotomy, numerous lymphocytes filtrated in the endoneurial area in distal transected stump in control, although the epineurial CD8+ cell accumulation has already diminished. In diabetes, on the other hand, endoneurial lymphocytes were significantly fewer (D 31 ± 8/mm2 vs. C 82 ± 16/mm2, P < 0.001). On the pathological evaluation, a progress of nerve fiber degeneration was suppressed in diabetes. Our results suggested that the inflammatory response during acute WD is reduced in experimental diabetes, which might be a reason for delayed WD in diabetic nerve.
Early Electrophysiological Changes In Transgenic Rat Model Of Charcot‐Marie‐Tooth
Authors: Grandis M , Abbruzzese M , Lunardi GL , Nobbio L , Mancardi GL , Leandri M , Schenone A.
Published: March 2003

Recently, a reliable transgenic rat model of human Charcot‐Marie‐Tooth type 1 A has been developed. So far, neurophysiological studies have been performed only in advanced stages of rat disease. Moreover, axonal involvement, which is known to occur in human CMT1A, has never been observed in this rat model. Affected rats show overexpression of Peripheral Myelin Protein (PMP‐22) and a peripheral hypomyelinating neuropathy. We perfomed an electrophysiological study in two heterozygous PMP‐22 transgenic rats and in one normal control, matched for age (3 weeks) and weight (average: 60 g). Recordings were performed in vivo by stimulating the sciatic nerve at both sciatic notch and ankle sites and recording the Hoffman reflex and direct muscle responses (CMAP). The H‐reflex related SNCV and MNCV were calculated by measuring the distance between the sciatic notch and the ankle sites and the respective latencies. The two transgenic rats showed different levels of PMP‐22 overexpression, as judged by quantitative PCR. The rat with a lower PMP‐22 gene level showed a 30% reduction of MNCV compared to the normal control, while SNCV was not reduced. The CMAP was sized approximately 45% of the normal rat while the ratio between H wave amplitude and CMAP was 30% of the normal, the H wave amplitude being more affected than the CMAP. The action potentials in the rat with a higher transgene level were not recordable. Our data demonstrate that slowing of MNCV is an early finding in the CMT1A rat model. The marked reduction of H wave amplitude in front of a normal SNCV suggests a possible early axonal damage of sensory fibers. The entity of electrophysiological compromission positively correlated with the number of copies for PMP‐22 gene. All together these considerations prove the sensitivity of this method, however further studies are needed to confirm these results and to prove that this model may be suitable to investigate the effects of therapeutic approaches.
CMT1A Associated With The 17p11.2 Duplication: Differential Features And Correlation
Authors: Pareyson D , Taroni F , Milani M , Scaioli V , Ciano C , Morbin M , Marchetti M , Lauria G , Sghirlanzoni A.
Published: March 2003

A duplication on chromosome 17p11.2 encompassing the gene coding for the peripheral myelin protein‐22 (PMP22) is the most common genetic abnormality underlying Charcot‐Marie‐Tooth disease (CMT). We report clinical and electrophysiologic features of our series of CMT1A patients harboring the duplication. There were 92 patients from 53 families representing 42% of all CMT index cases (n = 125) and 64% of CMT1 probands (n = 83). In CMT1A patients, mean age at onset was 9.7 ± 11.4 and was significantly lower than in non‐duplicated CMT1 cases (12.6 ± 9.7, p < 0.01) and CMT2 cases (21.5 ± 17, p < 0.001). Clinical severity was similar to that of CMT2 patients, but significantly milder than in non‐duplicated CMT1 cases. Pes cavus, upper limb involvement, deep tendon reflexes abnormalities, and sensory loss were more frequent compared to CMT2. Electrophysiologic examination revealed motor and sensory conduction velocity (MCV, SCV) slowing below 32 m/s in upper limbs. MCV and SCV were significantly lower than in non‐duplicated CMT1 patients. Amplitudes of upper limb compound muscle action potentials (CMAPs) and of upper and lower limb sensory action potentials (SAPs) were significantly lower than in CMT2, paralleling clinical differences. Clinical severity correlated with CMAP amplitudes and with disease duration. On the other hand, MCV slowing was not correlated with either severity or duration of the disease. We found a direct correlation between age at onset and upper limb MCV slowing. Conclusions: CMT1A is an early‐onset but slowly progressive disorder, on average milder than other CMT1. Axonal loss rather than demyelination per se underlies disease progression.
The Course And Prognostic Factors Of Familial Amyloid Polyneuropathy After Liver Transplantation
Authors: Adams D , Samuel D , Goulon‐Goeau C , Nakazato M , Costa PMP , Feray C , Plante V , Ducot B , Ichai P , Lacroix C , Metral S , Bismuth H , Said G.
Published: March 2003

Familial amyloid polyneuropathy (FAP) associated with mutations of the transthyretin (TTR) gene is the most common type of FAP, a devastating disease causing death within 10 years after the first symptoms. Because most of the amyloidogenic mutated TTR is secreted by the liver, transplantation is widely used to treat these patients, but long‐term quantitative evaluation of the effects of liver transplantation on the progression of the neuropathy are not available. We have treated 45 patients with symptomatic TTR‐FAP, including 43 with the Met30 TTR gene mutation, and report on the results of periodic evaluation of markers of neuropathy in 25 of them, who have been followed for more than 2 years after liver transplantation (mean follow‐up 3 years). The overall survival rates at 1 and 5 years were 82 and 60%, respectively. Urinary incontinence and a low Norris score at liver transplantation were associated with poorer outcome. The motor score stabilized in seven of 11 patients (64%) with mild sensorimotor neuropathy (walking unaided) and in two of the eight patients (25%) with severe sensorimotor deficit (walking with aid) at liver transplantation. In five other patients, deterioration of motor deficit occurred only within the first year after liver transplantation, but was progressive after this interval in two patients. None of the six patients with pure sensory neuropathy developed motor loss and superficial sensory loss remained unchanged. Two years after liver transplantation, the rate of myelinated axon loss in nerve biopsy specimens was markedly lower in seven transplanted patients (0.9/mm(2) of endoneurial area/month) than in non‐transplanted patients (70/nm(2) of endoneurial area/month). Symptoms of dysautonomia and quantitated cardiocirculatory autonomic tests remained unchanged. In all patients, serum mutated TTR decreased to 2.5% of pre‐liver transplantation values and remained at this level during follow‐up. We presently recommend liver transplantation in FAP patients at onset of first symptoms and exclusion of those with a Norris score below 55 and/or with urinary incontinence.