bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Williams syndrome face‐processing debate: the importance of building developmental trajectories
Authors: Karmiloff‐Smith Annette , Thomas Michael , Annaz Dagmara , Humphreys Kate , Ewing Sandra , Brace Nicola , Van Duuren Mike , Pike Graham , Grice Sarah , Campbell Ruth
Published: August 2004

Background: Face processing in Williams syndrome (WS) has been a topic of heated debate over the past decade. Initial claims about a normally developing (‘intact’) face‐processing module were challenged by data suggesting that individuals with WS used a different balance of cognitive processes from controls, even when their behavioural scores fell within the normal range. Measurement of evoked brain potentials also point to atypical processes. However, two recent studies have claimed that people with WS process faces exactly like normal controls.

Method: In this paper, we examine the details of this continuing debate on the basis of three new face‐processing experiments. In particular, for two of our experiments we built task‐specific full developmental trajectories from childhood to adolescence/adulthood and plotted the WS data on these trajectories.

Results: The first experiment used photos of real faces. While it revealed broadly equivalent accuracy across groups, the WS participants were worse at configural processing when faces were upright and less sensitive than controls to face inversion. In Experiment 2, measuring face processing in a storybook context, the face inversion effect emerged clearly in controls but only weakly in the WS developmental trajectory. Unlike the controls, the Benton Face Recognition Test and the Pattern Construction results were not correlated in WS, highlighting the different developmental patterns in the two groups. Again in contrast to the controls, Experiment 3 with schematic faces and non‐face stimuli revealed a configural‐processing deficit in WS both with respect to their chronological age (CA) and to their level of performance on the Benton.

Conclusion: These findings point to both delay and deviance in WS face processing and illustrate how vital it is to build developmental trajectories for each specific task.
nanos expression at the embryonic posterior pole and the medusa phase in the hydrozoan Podocoryne carnea
Authors: Torras Raquel , Yanze Nathalie , Schmid Volker , González‐Crespo Sergio
Published: August 2004

Summary
The distinction between soma and germline is an important process in the development of animals with sexual reproduction. It is regulated by a number of germline‐specific genes, most of which appear conserved in evolution and therefore can be used to study the formation of the germline in diverged animal groups. Here we report the isolation of two orthologs of one such gene, nanos (nos), in the cnidarian Podocoryne carnea, a species with representative zoological features among the hydrozoans. By studying nos gene expression throughout the Podocoryne biphasic life cycle, we find that the germline differentiates exclusively during medusa development, whereas the polyp does not contribute to the process. An early widespread nos expression in developing medusae progressively refines into a mainly germline‐specific pattern at terminal stages of medusa formation. Thus, the distinction between germline and soma is a late event in hydrozoan development. Also, we show that the formation of the medusa is a de novo process that relies on active local cell proliferation and differentiation of novel cell and tissue types not present in the polyp, including nos‐expressing cells. Finally, we find nos expression at the posterior pole of Podocoryne developing embryos, not related to germline formation. This second aspect of nos expression is also found in Drosophila, where nos functions as a posterior determinant essential for the formation of the fly abdomen. This raises the possibility that nos embryonic expression could play a role in establishing axial polarity in cnidarians.
Posterior Hypothalamic and Brainstem Activation in Hemicrania Continua
Authors: Matharu Manjit S. , Cohen Anna S. , McGonigle David J. , Ward Nick , Frackowiak Richard S. , Goadsby Peter J.
Published: August 2004

Objective.—To determine the brain structures involved in mediating the pain of hemicrania continua using positron emission tomography.

Background.—Hemicrania continua is a strictly unilateral, continuous headache of moderate intensity, with superimposed exacerbations of severe intensity that are accompanied by trigeminal autonomic features and migrainous symptoms. The syndrome is exquisitely responsive to indomethacin. Its clinical phenotype overlaps with that of the trigeminal autonomic headaches and migraine in which the hypothalamus and the brainstem, respectively, have been postulated to play central pathophysiologic roles. We hypothesized, based on the clinical phenotype, that hemicrania continua may involve activations in the hypothalamus, or dorsal rostral pons, or both.

Methods.—Seven patients with hemicrania continua were studied in two sessions each. In one session, the patients were scanned during baseline pain and when rendered completely pain free after being administered indomethacin 100 mg intramuscularly. In the other session, the patients were scanned during baseline pain and when still in pain after being administered placebo intramuscularly. Seven age‐ and sex‐matched nonheadache subjects acted as the control group. The scan images were processed and analyzed using SPM99.

Results.—There was a significant activation of the contralateral posterior hypothalamus and ipsilateral dorsal rostral pons in association with the headache of hemicrania continua. In addition, there was activation of the ipsilateral ventrolateral midbrain, which extended over the red nucleus and the substantia nigra, and bilateral pontomedullary junction. No intracranial vessel dilatation was obvious.

Conclusions.—This study demonstrated activations of various subcortical structures, in particular the posterior hypothalamus and the dorsal rostral pons. If posterior hypothalamic and brainstem activation are considered as markers of trigeminal autonomic headaches and migrainous syndromes, respectively, then the activation pattern demonstrated in hemicrania continua mirrors the clinical phenotype, with its overlap with trigeminal autonomic headaches and migraine.
Sinus Thrombosis After a Jump From a Small Rock and a Sneezing Attack: Minor Endothelial Trauma as a Precipitating Factor for Cerebral Venous Thrombosis?
Authors: Röttger Carina , Trittmacher Susan , Gerriets Tibo , Kaps Manfred , Stolz Erwin
Published: August 2004

Cerebral venous thrombosis (CVT) associated with minor or trivial head trauma has only been described in a few cases so far. We report two patients who developed CVT after a sudden intracranial pressure increase and head acceleration. A 49‐year‐old woman jumped from a small rock, 1 m in height, and developed instantaneous occipital headaches. Magnetic resonance imaging (MRI) confirmed confluens sinuum thrombosis. Risk factors consisted of smoking and oral contraceptives. Our second patient, an 18‐year‐old woman, experienced instantaneous headaches after a sneezing attack. Superior sagittal and right‐sided transverse sinus thrombosis were confirmed by venous computed tomography angiography. She took oral contraceptives as an additional risk factor. In about 20% of CVT cases the cause remains unclear. As minor head trauma may not have been recognized during history taking, this may represent a so far under‐recognized precipitating factor for CVT.
Learning from Diversity: A Theoretical Exploration
Authors: Foldy Erica Gabrielle
Published: August 2004

Public‐sector organizations tend to be more racially and ethnically diverse than private‐sector organizations, leading to the challenge of enhancing heterogeneous work group effectiveness. Recent work suggests that a group's “diversity perspective,” or set of beliefs about the role of cultural diversity, moderates diverse group performance. One perspective, the integration and learning perspective, argues that heterogeneous groups function better when they believe that cultural identities can be tapped as sources of new ideas and experiences about work. However, simply holding the integration and learning perspective may not be sufficient. Research on general group learning has shown that it requires particular behaviors and cognitive frames. This article integrates recent work on diversity perspectives with long‐standing research on team learning to propose a conceptual model of learning in culturally diverse groups. It suggests that both the integration and learning perspective and more generic learning frames and skills must be present.
Open Trial of Bupropion SR in Adolescent Major Depression
Authors: Glod Carol A. , Lynch Arlene , Flynn Elizabeth , Berkowitz Cynthia , Baldessarini Ross J.
Published: August 2004

PROBLEM There are few studies of sustained‐release bupropion in adolescents with major depression.

METHODS Twenty‐one adolescents with DSM‐IV major depression were recruited through advertisement and self‐referral; 11 began study medication and were rated weekly with an expanded Hamilton Depression Rating Scale (SIGH‐SAD), as well as Clinical Global Impression‐Improvement (CGI‐I).

RESULTS Of 11 subjects enrolled, 8 completed an8‐week trial of bupropion SR. Mean baseline SIGH‐SAD scores of 31–3 decreased significantly by 74% to mean endpoint score of 8–2. Improvement on CGI‐I that agreed closely between raters and patients was found in 8 of 11 subjects (72.3%). The mean daily dose of bupropion SR was 362 mg ± 52 mg and was well tolerated; insomnia and weight loss were experienced by 55%; other adverse effects of dry mouth, headache, agitation, light‐headedness, diarrhea, or rash were noted in a minority of subjects.

CONCLUSIONS In this preliminary, small open study, depressed adolescents showed a marked response to bupropion SR.
Paroxetine administration to influence human exercise capacity, perceived effort or hormone responses during prolonged exercise in a warm environment
Authors: Strachan A. T. , Leiper J. B. , Maughan R. J.
Published: August 2004

The purpose of the experiment was to examine whether selective serotonin (5‐HT) re‐uptake transporter blockade by paroxetine has any effect on perceived effort (RPE) during exercise or the time to reach volitional fatigue and on the prolactin and cortisol responses during prolonged exercise performed in a warm environment. Eight healthy males performed two cycle rides to exhaustion in a warm (32°C) environment at 60% of maximum oxygen uptake. Paroxetine (20 mg) or placebo was administered 5 h before exercise trials in a randomised double blind fashion. Time to exhaustion was not significantly influenced by administration of paroxetine: median (range) time to exhaustion was 93.3 (76.2–175.0) min on the placebo trial and 92.5 (66.0–151.0) min on the paroxetine trial. Rectal temperature was higher at rest and throughout exercise on the paroxetine trial. The serum concentrations of prolactin and cortisol were determined throughout exercise as peripheral markers of central 5‐HT activity. RPE increased over time but was not influenced by paroxetine administration. Prolactin and cortisol levels increased over time but paroxetine administration did not influence the hormone responses during exercise. In conclusion, acute administration of paroxetine failed to alter RPE, exercise capacity or the response of the determined peripheral hormone markers of central 5‐HT activity during prolonged exercise in a warm environment.
Tubular absorption of filtered cystatin‐C in the rat kidney
Authors: Roald Anca Beatrice , Aukland Knut , Tenstad Olav
Published: August 2004

As shown in previous studies, the two basic proteins aprotinin (Ap, 6.5 kDa) and cystatin (Cy, 13.3 kDa) can be used to estimate whole kidney glomerular filtration rate by measuring the renal cortical uptake relative to plasma concentration after I.V. injection. Local uptake of Ap can also be used to estimate local filtration rate, and the present experiments were undertaken to examine whether Cy would give a similar uptake pattern. Ap and Cy were labelled with 131I and 125I, respectively, and injected as an I.V. bolus. Frequent blood samples provided information on the filtered load. Five to 20 min after injection the kidney was clamped, frozen, and five tissue samples of 5–10 mg each were cut out from outer (OC), middle (MC) and inner cortex (IC) to be weighed and assessed for radioactivity. Five minute clearance ratios, Cy:Ap, were 1.36 ± 0.04, 1.27 ± 0.03 and 1.19 ± 0.04 in OC, MC and IC, respectively. The higher Cy clearance was expected from a higher glomerular filtrate:plasma ratio of the less basic Cy (Donnan distribution). However, this does not explain the increase of Cy:Ap clearances going from IC to the OC. A surplus of extracellular uptake of Cy in superficial layers was excluded, leading to the following interpretation. In all cortical layers the proximal convoluted tubule, i.e. the protein uptake segment, is located more superficially than its parent glomerulus. A longer uptake segment for Cy than for Ap will therefore lead to a relative greater transfer of filtered Cy from IC to MC, and from MC to OC. Anatomical studies on single nephrons presented in another article lend strong support to this interpretation.
Comparison of thermoregulatory responses to exercise in dry heat among prepubertal boys, young adults and older males
Authors: Inbar Omri , Morris Norman , Epstein Yoram , Gass Gregory
Published: August 2004

The purpose of this investigation was to compare the thermoregulatory responses during exercise in a hot climate among three age categories. Eight prepubertal (PP), eight young adult (Y) and eight elderly (O) male subjects cycled at an intensity of 50 ± 1% of their maximum oxygen uptake

for 85 min (three 20 min bouts with three 7 min rest periods) in hot and dry conditions (41 ± 0.67°C, 21 ± 1% relative humidity). During the exercise‐in‐heat protocol, rectal temperature (Tre) skin temperatures (Tsk), heart rate (HR),

, RER, sweat rate, and the number of heat activated sweat glands (HASG) were determined. Despite highest and lowest end‐exposure Tre in the Y and O groups, respectively, the rise in rectal temperature (accounting for differences in baseline Tre) was similar in all age groups. Changes in body heat storage (ΔS), both absolute and relative to body mass, were highest in the Y and O groups and lowest in the PP group. While end‐session as well as changes in mean skin temperature were similar in all three age groups, HR (absolute and percentage of maximum) was significantly lower for the O compared with the PP and Y groups. Total body as well as per body surface sweating rate was significantly lower for the PP group, while body mass‐related net metabolic heat production ((M−W) kg−1) and heat gained from the environment were highest in the PP and lowest in the O group. Since mass‐related evaporative cooling (Esk kg−1) and sweating efficiency (Esk/Msw kg−1) were highest in the PP and lowest in the O group, the mass‐dependent heat stored in the body (ΔS kg−1) was lowest in the PP (1.87 ± 0.03 W kg−1) and highest in Y and O groups (2.19 ± 0.08 and 1.97 ± 0.11 W kg−1, respectively). Furthermore, it was calculated that while the O group required only 4.1 ± 0.5 W of heat energy to raise their body core temperature by 1°C, and the Y group needed 6.9 ± 0.9 W (1°C)−1, the PP group required as much as 12.3 ± 0.7 W to heat up their body core temperature by 1°C. These results suggest that in conditions similar to those imposed during this study, age and age‐related characteristics affect the overall rate of heat gain as well as the mechanisms through which this heat is being dissipated. While prepubertal boys seem to be the most efficient thermoregulators, the elderly subjects appear to be the least efficient thermoregulators.
Increased allopregnanolone levels in the fetal sheep brain following umbilical cord occlusion
Authors: Nguyen Phuong N. , Yan Edwin B. , Castillo‐Melendez Margie , Walker David W. , Hirst Jonathan J.
Published: August 2004

Allopregnanolone (AP) is a potent modulator of the GABAA receptor. Brain AP concentrations increase in response to stress, which is thought to provide neuroprotection by reducing excitation in the adult brain. Umbilical cord occlusion (UCO) causes hypoxia and asphyxia in the fetus, which are major risk factors associated with poor neurological outcome for the neonate, and may lead to adverse sequelae such as cerebral palsy. The aims of this study were as follows: (i) to determine the effect of 10 min UCO on AP concentrations in the extracellular fluid of the fetal brain using microdialysis, and (ii) to compare the content of the steroidogenic enzymes P450scc and 5α‐reductase type II (5αRII) with brain and CSF neurosteroid concentrations. UCO caused fetal asphyxia, hypertension, bradycardia and respiratory acidosis, which returned to normal levels after 1–2 h. AP concentrations in dialysate samples from probes implanted in grey and white matter of the parietal cortex were significantly increased 1 h after UCO from control levels of 10.4 ± 0.4 and 12.4 ± 0.3 to 26.0 ± 5.1 and 27.6 ± 6.4 nmol l−1, respectively (P < 0.05), before returning to pre‐occlusion levels by 3–4 h after UCO. When fetal brains were collected 1 h after a 10 min UCO, the relative increases of AP and pregnenolone content in the parietal cortex were similar to the increase observed in the extracellular (dialysate) fluid. AP, but not pregnenolone, was increased in CSF at this time. P450scc and 5αRII enzyme expression was significantly increased in the cerebral cortex in the UCO fetuses compared to control fetuses. These results suggest that the fetal brain is capable of transiently increasing neurosteroid production in response to asphyxia. The action of the increased neurosteroid content at GABAA receptors may serve to diminish the increased excitation due to excitotoxic amino acid release, and provide short‐term protection to brain cells during such stress.
Influence of visual experience on developmental shift from long‐term depression to long‐term potentiation in the rat medial vestibular nuclei
Authors: Grassi Silvarosa , Dieni Cristina , Frondaroli Adele , Pettorossi Vito Enrico
Published: August 2004

The influence of visual experience deprivation on changes in synaptic plasticity during postnatal development was studied in the ventral part of the rat medial vestibular nuclei (vMVN). We analysed the differences in the occurrence, expressed as a percentage, of long‐term depression (LTD) and long‐term potentiation (LTP) induced by high frequency stimulation (HFS) of the primary vestibular afferents in rats reared in the light (LR) and those in the dark (DR). In LR rats, HFS only induced LTD in the early stages of development, but the occurrence of LTD progressively decreased to zero before their eyes opened, while that of LTP enhanced from zero to about 50%. Once the rats' eyes had opened, LTD was no longer inducible while LTP occurrence gradually reached the normal adult value (70%). In DR rats, a similar shift from LTD to LTP was observed before their eyes opened, showing only a slightly slower LTD decay and LTP growth, and the LTD annulment was delayed by 1 day. By contrast, the time courses of LTD and LTP development in DR and LR rats showed remarkable differences following eye opening. In fact, LTD occurrence increased to about 50% in a short period of time and remained high until the adult stage. In addition, the occurrence of LTP slowly decreased to less than 20%. The effect of light‐deprivation was reversible, since the exposure of DR rats to light, 5 days after eye opening, caused a sudden disappearance of LTD and a partial recover of LTP occurrence. In addition, we observed that a week of light deprivation in LR adult rats did not affect the normal adult LTP occurrence. These results provide evidence that in a critical period of development visual input plays a crucial role in shaping synaptic plasticity of the vMVN, and suggest that the visual guided shift from LTD to LTP during development may be necessary to refine and consolidate vestibular circuitry.
Etomidate elevates intracellular calcium levels and promotes catecholamine secretion in bovine chromaffin cells
Authors: Xie Z. , Currie K. P. M. , Fox A. P.
Published: August 2004

Etomidate, an intravenous imidazole general anaesthetic, is thought to produce anaesthesia by modulating or activating ionotropic Cl−‐permeable GABAA receptors. Chromaffin cells are known to express functional GABAA receptors with properties similar to their neuronal counterparts. We have shown that activation of the GABAA receptors, with specific GABAA agonists, leads to cellular excitation. Our goal was to determine whether etomidate mimicked this response and to explore the functional consequences of this activation. Imaging experiments with the Ca2+‐indicator dye fura‐2 were used to assay [Ca2+]i. Bovine adrenal chromaffin cells were superfused with a variety of GABAA‐selective drugs to determine their effects on [Ca2+]i. Amperometric measurements were used to assay catecholamine release in real‐time. We show that bovine adrenal chromaffin cells were excited by etomidate at clinically relevant concentrations. Etomidate directly activated GABAA receptors found in chromaffin cells thereby elevating [Ca2+]i. The effects of etomidate were mimicked by the specific GABAA agonist muscimol and blocked by the specific antagonist bicuculline. Our data show that low concentrations of etomidate modulated GABAA receptor activation by muscimol. Blockade of voltage‐dependent Ca2+ channels prevented the elevation of [Ca2+]i by GABA. Application of etomidate directly to the chromaffin cells elicited robust catecholamine secretion from these cells. The data indicate that clinically relevant concentrations of etomidate can directly activate GABAA receptors, which, due to the positive anion equilibrium potential, depolarizes chromaffin cells. This depolarization activates voltage‐dependent Ca2+ channels thereby stimulating catecholamine release. Our data suggest that circulating catecholamine levels may be elevated after etomidate application.
The Structure of Catalytically Active Gold on Titania
Authors: Chen M. S. , Goodman D. W.
Published: August 2004

The high catalytic activity of gold clusters on oxides has been attributed to structural effects (including particle thickness and shape and metal oxidation state), as well as to support effects. We have created well-ordered gold mono-layers and bilayers that completely wet (cover) the oxide support, thus eliminating particle shape and direct support effects. High-resolution electron energy loss spectroscopy and carbon monoxide adsorption confirm that the gold atoms are bonded to titanium atoms. Kinetic measurements for the catalytic oxidation of carbon monoxide show that the gold bilayer structure is significantly more active (by more than an order of magnitude) than the monolayer.
Demystified… recombinant antibodies
Authors: Smith K A , Nelson P N , Warren P , Astley S J , Murray P G , Greenman J
Published: August 2004

Recombinant antibodies are important tools for biomedical research and are increasingly being used as clinical diagnostic/therapeutic reagents. In this article, a background to humanised antibodies is given, together with details of the generation of antibody fragments—for example, single chain Fv fragments. Phage antibody fragments are fast becoming popular and can be generated by simple established methods of affinity enrichment from libraries derived from immune cells. Phage display methodology can also be used for the affinity enrichment of existing antibody fragments to provide a reagent with a higher affinity. Here, phage antibodies are demystified to provide a greater understanding of the potential of these reagents and to engage clinicians and biomedical scientists alike to think about potential applications in pathology and clinical settings.
Resolution of chronic severe refractory thrombocytopenia after treatment of hypothyroidism
Authors: Bowles K M , Turner G E , Wimperis J Z
Published: August 2004

The case of a 52 year old woman with chronic severe refractory thrombocytopenia is presented. Over a three year period, her platelet count was persistently less than 20 × 109/litre (normal range, 150–400). She required repeated hospital admission for management of bleeding and received multiple blood transfusions. She was given repeated courses of steroids, immunosuppression, immunoglobulin, and splenectomy, without success, in an attempt to stop the chronic blood loss. Eventually, she was found to be profoundly hypothyroid. On correction of her thyroid deficiency the platelet count returned to the normal range and all bleeding stopped. The platelet count remains in the normal range three years later.
Supervised automated microscopy increases sensitivity and efficiency of detection of sentinel node micrometastases in patients with breast cancer
Authors: Mesker W E , Torrenga H , Sloos W C R , Vrolijk H , Tollenaar R A E M , de Bruin P C , van Diest P J , Tanke H J
Published: August 2004

Aims:To investigate the practicality and sensitivity of supervised automated microscopy (AM) for the detection of micrometastasis in sentinel lymph nodes (SLNs) from patients with breast carcinoma.

Methods:In total, 440 SLN slides (immunohistochemically stained for cytokeratin) from 86 patients were obtained from two hospitals. Samples were selected on the basis of: (1) a pathology report mentioning micrometastases or isolated tumour cells (ITCs) and (2) reported as negative nodes (N0).

Results:From a test set of 29 slides (12 SLN positive patients, including positive and negative nodes), 18 slides were scored positive by supervised AM and 11 were negative. Routine examination revealed 17 positive slides and 12 negative. Subsequently, automated reanalysis of 187 slides (34 patients; institute I) and 216 slides (40 patients; institute II) from reported node negative (N0) patients showed that two and seven slides (from two and five patients, respectively) contained ITCs, respectively, all confirmed by the pathologists, corresponding to 5.9% and 12.5% missed patients. In four of the seven missed cases from institute II, AM also detected clusters of four to 30 cells, but all with a size ⩽ 0.2 mm.

Conclusions:Supervised AM is a more sensitive method for detecting immunohistochemically stained micrometastasis and ITCs in SLNs than routine pathology. However, the clinical relevance of detecting cytokeratin positive cells in SLNs of patients with breast cancer is still an unresolved issue and is at the moment being validated in larger clinical trials.
The predictive value of total serum IgE for a positive allergen specific IgE result
Authors: Sinclair D , Peters S A
Published: August 2004

Background:Measurement of total serum IgE and allergen specific IgE is often requested to assess possible allergy. As public awareness increases, so do requests for allergy assessment; unless there is a clear “allergen suspect” in the history, several allergen specific IgE requests may be made. This increases the likelihood of detecting borderline increases in allergen specific IgE of uncertain relevance, and has important cost implications for the service.

Aims:To provide an evidence base for this observation.

Methods:In this retrospective observational study, results from 301 patients under 16 years of age from whom blood was taken for “allergy testing” from March 2001 to February 2003 were studied.

Results:Allergen specific IgE testing in children with low total serum IgE concentrations (<10 IU/litre) yielded very few positive results (three of 73 children), except in those being investigated for an acute reaction to a single food; when IgE was 11–20 kU/litre, 13 of 73 children had positive allergen specific IgE; in the 21–40 kU/litre IgE group, 16 of 74 children had positive allergen specific IgE and in the 41–80 kU/litre group, 22 of 81 had positive allergen specific IgE.

Conclusions:Allergen specific IgE testing in children with low IgE concentrations (<10 kU/litre) produces few positive results in patients with non-specific symptoms. Laboratories should perform allergy testing for specific allergens regardless of total IgE concentration only when there are convincing clinical reasons to do so, and should not proceed with this if the total IgE is <10 kU/litre and the presenting symptoms are non-specific.
Serrated adenomas of the appendix
Authors: Rubio C A
Published: August 2004

Aims:A review of the literature indicated that only one case of serrated adenoma of the appendix has been recorded. The aim was to explore the possible occurrence of serrated adenomas of the appendix at the department of pathology, Karolinska Institute and University Hospital, Stockholm, Sweden.

Methods:Between January 1993 and December 2003, 38 non-carcinoid, non-neoplastic, or neoplastic polyps or tumours of the appendix were surgically removed at this hospital. All filed histological sections (haematoxylin and eosin stained) were reviewed.

Results:Of the 38 lesions, four were hyperplastic polyps, 10 serrated adenomas, six villous adenomas, and the remaining eight mucinous adenocarcinomas without a remnant adenoma. Serrated adenomas accounted for six of the 11 adenomas without invasion, and four of the 15 adenomas with invasive carcinoma. At the time of surgical resection, four of the 10 serrated adenomas had evolved into invasive carcinomas, in addition to 11 of the 16 villous adenomas.

Conclusions:Serrated and villous adenomas of the appendix appear to be highly aggressive lesions, more aggressive than similar adenomas in the colon and rectum. Of the seven cases with a hyperplastic polyp, one concurred with a serrated adenoma, two with a serrated adenoma having an invasive carcinoma, and one with invasive carcinoma without a remnant adenomatous structure. At present, there is an increased awareness that some hyperplastic polyps of the colon and rectum may evolve into serrated adenomas. Whether this pathway is also valid for the appendix vermiformis should be investigated in a larger number of cases.
Late Holocene syngenetic ice-wedge polygons development, Bylot Island, Canadian Arctic Archipelago
Authors: Fortier Daniel , Allard Michel
Published: August 2004

The initial configuration of the syngenetic ice-wedge polygons that developed in the outwash plain of glacier C-79 after 6000 BP was modified by the accumulation of wind-blown and organic sediments that began after 3670 ± 110 BP. The late Holocene sedimentation led to an increase in the thermal contraction coefficient of the soil and the formation of third- and fourth-order contraction cracks, partially explaining the current configuration of the polygonal network. The upturning of the sedimentary strata bordering the ice wedges was associated with the summer thermal expansion and resulting internal creep of the soil. The mean annual soil displacement coefficient was in the order of 2.52.7 × 105 /°C at the thousand-year scale. The late Holocene sedimentary strata under the centre of the polygons were undisturbed, which will make it possible to use this sedimentary record in further studies to attempt paleoenvironmental reconstructions from cores.
The PotsdamBeekmantown Group boundary, Nepean Formation type section (Ottawa, Ontario): a cryptic sequence boundary, not a conformable transition
Authors: Dix George R , Hersi Osman Salad , Nowlan Godfrey S
Published: August 2004

There are two unreconciled interpretations for the age and character of the boundary separating the CambrianOrdovician Potsdam and Beekmantown groups that underlie the Ottawa Embayment in eastern Ontario. These stratal groups consist of interior facies of the central Laurentian Platform. As exposed in the type section of the Nepean Formation (upper Potsdam Group), located in the City of Ottawa, the boundary was previously interpreted to be conformable and of Early Ordovician age. This intepretation was of enormous impact on subsequent regional geology compilations that showed a diachronous boundary across the platform interior. From recent subsurface analysis across eastern Ontario, the contact was interpreted to be disconformable, a sequence boundary separating Late Cambrian and Early Ordovician strata. This paper reexamines the type section. Lithologically, the group boundary should be repositioned downsection by ~1.5 m. The contact now lies coincident with a disconformity that has a paleorelief of < 10 cm. The proposed revision is geologically significant. Previous collections of Early Ordovician conodonts from the type section, used to define the age of what had been interpreted to be upper Potsdam strata, now fall entirely within the lower Beekmantown Group. Nepean (Potsdam) strata exposed in the type section remain undated. Regional correlation of the disconformity across the Laurentian platform suggests that Nepean strata at the type section are likely of Late Cambrian age. There now exists a regionally coherent separation of Cambrian and Ordovician sedimentation patterns in the Ottawa Embayment.
An unusually large Aulocopella winnipegensis and associated demosponges from the Upper Ordovician Beaverfoot Formation, southeastern British Columbia
Authors: Rigby J Keith , Johnston Paul A
Published: August 2004

An unusually large specimen of the rare digitate to bladed Aulocopella winnipegensis Rauff and three relatively normal sized specimens of ashtray-shaped Hudsonospongia? sp. constitute the first record of demosponges from the Upper Ordovician Beaverfoot Formation in southeastern British Columbia and the first record of these taxa from western Canada. Gross form and canal structure are well preserved, but dolomitization and (or) coarse microsphaeroidal silicification have obliterated spicules and other structural details. We interpret these sponges as epifaunal recliners, without means of attachment to the substrate, a life mode rarely encountered in the modern sponge biota.
NOVEL SPINTRONIC MATERIALS BASED ON FERROMAGNETIC SEMICONDUCTOR CHALCOPYRITES
Authors: MEDVEDKIN G. A. , GOLOSHCHAPOV S. I. , VOEVODIN V. G. , SATO K. , ISHIBASHI T. , MITANI S. , TAKANASHI K. , FUJIMORI A. , ISHIDA Y. , OKABAYASHI J. , SARMA D. D. , AKAI H. , KAMATANI T.
Published: August 2004

Ternary diamond-like compounds in II–IV–V2 semiconductor system heavily-doped with transition d-element Mn have been recently prepared. The materials grown in both forms — single crystal layers and polycrystalline bulks — exhibit well defined ferromagnetic hysteresis with a saturation behavior in the magnetization curve up to above room temperature. Curie temperatures are of TC=310 K to 320 K for ( Cd 1-x Mn x) GeP 2 and ( Zn 1-x Mn x) GeP 2 compounds. The chemical states in the bulk of ZnGeP 2: Mn and interface of Mn -doped ferromagnetic layer on ZnGeP 2 (001) crystal, have been clarified by electron paramagnetic resonance and in situ photoemission spectroscopy. The as-prepared surface consists of Ge -rich, metallic Mn -compound. In and below the sub-surface region, dilute Mn 2+ species as precursors of the DMS phase exist. Mn 2+ ions are paramagnetic active on Zn 2+ sites in the bulk and show five EPR sets of equidistant peaks. Theoretical band-gap calculation suggests a predominant antiferromagnetic order in stoichiometric ( Cd , Mn ) GeP 2 but the systems with vacancies as ( Cd , V C , Mn ) GeP 2 or ( Cd , Ge , Mn ) GeP 2 are ferromagnetic and energetically stable. These materials are of great promise for room-temperature spintronics applications.
EXTRAORDINARY HALL EFFECT IN ULTRA-THIN Fe–Pt FILMS AND FABRICATION OF NANOMICRO HALL DEVICES
Authors: MATVEEV V. N. , BEREZIN V. A. , VOLKOV V. T. , FIRSOV A. A. , KONONENKO O. V. , LEVASHOV V. I.
Published: August 2004

Fe – Pt alloy thin and ultra thin films were deposited by the pulse laser evaporation method. Micronano Hall devices were fabricated from ultra thin films by an Ar plasma etching process using electron beam lithography procedures. The extraordinary Hall effect (EHE) in Fe – Pt alloy thin and ultra thin films and micronano Hall devices was investigated. The film thickness reduction is found to cause an increase in Hall voltage, which means an enhancement of field sensitivity of the Hall sensor. Maximum sensitivity S=260 Ω/ T was measured in ultra thin film with thickness d=20 Å.
Catecholamine response is attenuated during moderate-intensity exercise in response to the “lactate clamp”
Authors: Fattor Jill A. , Miller Benjamin F. , Jacobs Kevin A. , Brooks George A.
Published: August 2004

Catecholamine release is known to be regulated by feedforward and feedback mechanisms. Norepinephrine (NE) and epinephrine (Epi) concentrations rise in response to stresses, such as exercise, that challenge blood glucose homeostasis. The purpose of this study was to assess the hypothesis that the lactate anion is involved in feedback control of catecholamine concentration. Six healthy active men (26 ± 2 yr, 82 ± 2 kg, 50.7 ± 2.1 ml·kg−1·min−1) were studied on five occasions after an overnight fast. Plasma concentrations of NE and Epi were determined during 90 min of rest and 90 min of exercise at 55% of peak O2 consumption (V̇o2 peak) two times with exogenous lactate infusion (lactate clamp, LC) and two times without LC (CON). The blood lactate profile (∼4 mM) of a preliminary trial at 65% V̇o2 peak (65%) was matched during the subsequent LC trials. In resting men, plasma NE concentration was not different between trials, but during exercise all conditions were different with 65% > CON > LC (65%: 2,115 ± 166 pg/ml, CON: 1,573 ± 153 pg/ml, LC: 930 ± 174 pg/ml, P < 0.05). Plasma Epi concentrations at rest were different between conditions, with LC less than 65% and CON (65%: 68 ± 9 pg/ml, CON: 59 ± 7 pg/ml, LC: 38 ± 10 pg/ml, P < 0.05). During exercise, Epi concentration showed the same trend (65%: 262 ± 37 pg/ml, CON: 190 ± 34 pg/ml, LC: 113.2 ± 23 pg/ml, P < 0.05). In conclusion, lactate attenuates the catecholamine response during moderate-intensity exercise, likely by feedback inhibition.
Intracoronary administration of FGF-2: a computational model of myocardial deposition and retention
Authors: Filion Renee J. , Popel Aleksander S.
Published: August 2004

This study uses a computational model to characterize the myocardial deposition and retention of basic fibroblast growth factor (FGF-2) at the cellular level after intracoronary (IC) administration of exogenous FGF-2. The model is applied to the in situ conditions present within the myocardium of a dog for which the plasma pharmacokinetics resulting from IC injection of FGF-2 were recorded. Our estimates show that the processes involved in FGF-2 signaling are not diffusion limited; rather, the response time is determined by the reaction time of FGF-2 binding to cell surface receptors. Additionally, the processes of receptor secretion and internalization are found to play crucial roles in the FGF-2 dynamics; future experiments are required to quantify these processes. The model predictions obtained in this study suggest that IC administration of FGF-2 via either a single bolus or repetitive injections causes a transient increase (time scale of hours) in myocardial FGF-2 concentration if the endogenous level of free interstitial FGF-2 is low enough to allow permeation of FGF-2 molecules from the microvascular to the interstitial spaces. The model shows that the majority (64%) of the extracellular FGF-2 ligands are located within the interstitium, and similar fractions are found in the basement membrane and extracellular matrix. Among the FGF-2 molecules found within the interstitium, 2% are free and 98% are bound to interstitial heparan sulfate proteoglycans. These results support the theory of extracellular control of the bioavailability of FGF-2 via dynamic storage of FGF-2 within the basement membrane and extracellular matrix.
Enhanced IGF-1 expression improves smooth muscle cell engraftment after cell transplantation
Authors: Liu Tian-Biao , Fedak Paul W. M. , Weisel Richard D. , Yasuda Tamotsu , Kiani Gholam , Mickle Donald A. G. , Jia Zhi-Qiang , Li Ren-Ke
Published: August 2004

The functional benefit of cell transplantation after a myocardial infarction is diminished by early cell losses. IGF-1 enhances cell proliferation and survival. We hypothesized that IGF-1-transfected smooth muscle cells (SMCs) would enhance cell survival and improve engraftment after cell transplantation. The IGF-1 gene was transfected into male SMCs and compared with SMCs transfected with a plasmid vector (vector control) and nontransfected SMCs (cell control). IGF-1 mRNA ( n = 10/group) and protein levels ( n = 6/group) were higher ( P < 0.05 for all groups) at 3, 7, and 14 days compared with controls. VEGF was also increased in parallel to enhanced IGF-1 expression. IGF-1-transfected cells demonstrated greater cell proliferation, stimulated angiogenesis, and decreased caspase-3 activity after simulated ischemia and reperfusion ( P < 0.05 for all groups compared with vector or cell controls). A uniform left ventricular injury was produced in female rats using a cryoprobe. Three weeks later, 2 × 106cells from three groups were implanted into the scar. One week later, IGF-1-transfected SMCs had increased myocardial IGF-1 and VEGF levels, increased Bcl2expression, limited cell apoptosis, and enhanced vessel formation in the myocardial scar compared with the two control groups ( P < 0.05 for all groups). The proportion of SMCs surviving in the implanted region was greater ( P < 0.05) in the IGF-1-transfected group than in the vector or cell controls. Gene enhancement with IGF-1 improved donor cell proliferation, survival, and engraftment after cell transplantation, perhaps mediated by enhanced angiogenesis and reduced apoptosis.
Chronic ANG II infusion increases NO generation by rat descending vasa recta
Authors: Zhang Zhong , Rhinehart Kristie , Solis Glen , Pittner Janos , Lee-Kwon Whaseon , Welch William J. , Wilcox Christopher S. , Pallone Thomas L.
Published: August 2004

We tested whether chronic ANG II infusion into rats affects descending vasa recta (DVR) contractility, synthesis of superoxide, or synthesis of nitric oxide (NO). Rats were infused with ANG II at 250 ng·kg−1·min−1 for 11–13 days. DVR were loaded with dihydroethidium (DHE) to measure superoxide and 3-amino-4-aminomethyl-2′,7′-difluorofluorescein (DAFFM) to measure NO. Acute constriction of DVR by ANG II (0.1, 1, and 10 nM) was diminished, and NO generation rate was raised by chronic ANG II infusion. DHE oxidation by DVR from ANG II-infused rats was similar to controls and was significantly higher when NO synthesis was prevented with Nω-nitro-l-arginine methyl ester (l-NAME). The superoxide dismutase mimetic Tempol (1 mM) increased NO generation compared with controls. The increased synthesis of NO by chronic ANG II-treated vessels persisted in the presence of Tempol. DVR endothelial cytoplasmic Ca2+ response to ACh was diminished by chronic ANG II treatment, but the capacity of ACh to increase NO generation was unaltered. We conclude that DVR generation of superoxide is not affected by chronic ANG II exposure but that basal NO synthesis is increased. DVR superoxide is unlikely to be an important mediator of chronic ANG II slow pressor hypertension in rats.
Glycine intake decreases plasma free fatty acids, adipose cell size, and blood pressure in sucrose-fed rats
Authors: Hafidi Mohammed El , Pérez Israel , Zamora Jose , Soto Virgilia , Carvajal-Sandoval Guillermo , Baños Guadalupe
Published: August 2004

The study investigated the mechanism by which glycine protects against increased circulating nonesterified fatty acids (NEFA), fat cell size, intra-abdominal fat accumulation, and blood pressure (BP) induced in male Wistar rats by sucrose ingestion. The addition of 1% glycine to the drinking water containing 30% sucrose, for 4 wk, markedly reduced high BP in sucrose-fed rats (SFR) (122.3 ± 5.6 vs. 147.6 ± 5.4 mmHg in SFR without glycine, P < 0.001). Decreases in plasma triglyceride (TG) levels (0.9 ± 0.3 vs. 1.4 ± 0.3 mM, P < 0.001), intra-abdominal fat (6.8 ± 2.16 vs. 14.8 ± 4.0 g, P < 0.01), and adipose cell size were observed in SFR treated with glycine compared with SFR without treatment. Total NEFA concentration in the plasma of SFR was significantly decreased by glycine intake (0.64 ± 0.08 vs. 1.11 ± 0.09 mM in SFR without glycine, P < 0.001). In control animals, glycine decreased glucose, TGs, and total NEFA but without reaching significance. In SFR treated with glycine, mitochondrial respiration, as an indicator of the rate of fat oxidation, showed an increase in the state IV oxidation rate of the β-oxidation substrates octanoic acid and palmitoyl carnitine. This suggests an enhancement of hepatic fatty acid metabolism, i.e., in their transport, activation, or β-oxidation. These findings imply that the protection by glycine against elevated BP might be attributed to its effect in increasing fatty acid oxidation, reducing intra-abdominal fat accumulation and circulating NEFA, which have been proposed as links between obesity and hypertension.
Effects of periconceptional undernutrition on the initiation of parturition in sheep
Authors: Kumarasamy Vasumathy , Mitchell Murray D. , Bloomfield Frank H. , Oliver Mark H. , Campbell Melanie E , Challis John R. G. , Harding Jane E.
Published: August 2004

In sheep, parturition is initiated by increased fetal hypothalamic-pituitary-adrenal axis (HPAA) activity leading to PGE2 and PGF2α production and a rise in the 17β-estradiol-progesterone (E2/P4) ratio. Uteroplacental PG production can also increase fetal HPAA activity. Periconceptional maternal undernutrition accelerates fetal HPAA maturation resulting in preterm labor. We determined whether preterm labor was preceded by an increase in PG concentrations and E2/P4 ratio and whether these increases preceded or followed the corresponding rise in cortisol concentrations. Singleton-bearing ewes were nourished ad libitum (N, n = 9) or undernourished (UN, n = 10) to reduce maternal weight by 15% from −61 days (d) to +30 d after mating with ad libitum intake thereafter. Paired maternal and fetal blood samples were collected from 126 d until delivery. Half the UN group delivered prematurely (>2 SD below mean gestation for the flock). PG and cortisol concentrations and E2/P4 ratio increased before delivery in the same way in both groups. However, the increases occurred 7–10 d earlier in UN than in N animals. In both UN and N fetuses cortisol concentrations rose before fetal and maternal PG concentrations and maternal E2/P4 ratio. Periconceptional maternal undernutrition induces preterm delivery in sheep by advancing the expected prepartum rise in cortisol and PG concentrations and E2/P4 ratio. The rise in fetal cortisol concentration precedes the rise in fetal and maternal PG concentrations and maternal E2/P4 ratio, suggesting that the underlying mechanism is likely to be acceleration of fetal HPAA maturation, resulting in initiation of the normal process of parturition.