bluuebunny/crossref_metadata_2025 huggingface dataset:
IV. A letter from Mr. Jos. Nelson, concerning the effects of the abovementioned storm of thunder and lightning at Colchester
Authors: Nelson Jos
Published: December 2006

Sir, Having taken notice of the Strange Effects of Thunder you Published for the Months of
January
and
February
last, the like was strange in this Town of
Colchester
.
I. A relation of an idiot at Ostend; with two other chirurgical cases
Authors: Amijand Claud
Published: December 2006

Tis now about five Weeks, since an Idiot from his Infancy died at
Ostend
, the place of his Birth, in the 33d Year of his Age; his Death having been preceded with twelve Days continual remitting Fever, and a considerable Tumour and Pain about the Region of the Liver.
VIII. De variis animalibus philippensibus, ex MSS. R. P. Geo. Jos. Camelli. Communicavit D. Jac. Petiver, S. R. S
Authors: Camelli Geo.. Jos.
Published: December 2006

De Ranis, Bufonibus, Lacertis, Testudinibus, & c.
I. Microscopical observations on the palates of oxen, & c
Authors: Leeuwenhoek Antoni Van
Published: December 2006

I Took a Cow's or Oxe's Head, and cut out of the Mouth of it the Roof or Palate, close to the Throat, while it was yet warm; and having prest it gently, I cou'd perceive that there issued out of several Parts of it, small, round, protuberant, and transparent Drops; and having prest it a little harder, there followed a yellow Moisture.
IX. An account of books; viz. I. Preælectiones chymicæ oxoniæ habitæ a Johanne Freind, M. D. Ædis christi alumno. II. An account of animal secretion, the quantity of of blood in the human body, and muscular motion. By James Keill, M. D
Authors: Freind John
Published: December 2006

Tho’ the Art of Chymistry is at present much improved, and abounds with many excellent and useful Experiments; yet it must be acknowledg’d, that hitherto there has been made but a very little Progress in the Philosophy of it; and that Men are still to seek for the Reasons of the many strange Phænomena it produces.
V. An explanation of the figures of a pagan temple and unknown characters at Cannara in Salset.
Authors: Stuart Alexander
Published: December 2006

The rocky Mountain Cannara in the Island of Salset, belonging to the Portuguese, with the Temple and Caverns.
V. An extract of an other letter from Mr. James Yonge, upon the same subjects as the former
Authors: Yonge James
Published: December 2006

Honoured Sir, The Anomalar Blackness of the Girl’s Face, of which I sent the History, is now divided into a few dark, clowdy Specks; which appear but seldom, and nothing so livid as formerly.
VIII. A letter from Mr. Anth. Van Leeu­wenhoek, F. R. S. containing some microscopical observations on the particles of chrystalliz'd sugar, &c. and his manner of observing the circulation of the blood in an eel
Authors: Leeuwenhoek Antoni Van
Published: December 2006

I Send you herewith my last Remarks, concerning the Coagulation of Sugar, which I had traced upon Paper near Three Years ago, and caused them to be Engrav’d upon a Copper-Plate, after that my Painter had Drawn them.
V. The Croonian Lecture. On the structure of a muscular fibre from which is derived its elongation and contraction
Authors: Home Everard
Published: December 2006

In the course of the last 40 years I have given this Lecture more frequently than any Member of the Society; and, like my predecessors, on those occasions, have taken up the subjects most nearly connected with the inquiry for which the Lecture was instituted. As far back as the year 1818, while considering the mode in which coagulated blood is rendered vascular, I brought forward a magnified drawing of a muscular fibre made by Mr. Bauer, showing it to be composed of a single row of globules 1/2000 parts of an inch in diameter, or in other words, of red globules deprived of their colouring matter.
IX. Observations on the poison of the common toad
Authors: Davy John
Published: December 2006

In every country in which this animal is found, it is considered poisonous by the common people; and the opinion may be traced back to a very remote antiquity. Of late years the notion has been rejected by the professed naturalist, and placed in the number of vulgar prejudices. Thus, M. Cuvier speaking of the common toad, remarks: “Cesont des animaux d’une forme hideuse, dégoûtante, que Ton accuse mal-à-propos d’être venimeux par leur salive, leur morsure leur urine, et même par l’humeur qu’il transpirent.” In this, as in some other instances, the common and long received opinion is well founded, and that of the philosopher hastily and erroneously formed.
XXIX. On the existence of a limit to vaporization
Authors: Faraday Michael
Published: December 2006

It is well known that within the limits recognised by experiment, the constitution of vapour in contact with the body from which it rises, is such, that its tension increases with increased temperature, and diminishes with diminished temperature; and, though in the latter case we can, with many substances, so far attenuate the vapour as soon to make its presence inappreciable to our tests, yet an opinion is very prevalent, and I believe general, that still small portions are produced; the tension being correspondent to the comparatively low temperature of the substance. Upon this view, it has been supposed that every substance in vacuo or surrounded by vapour or gas, having no chemical action upon it, has an atmosphere of its own around it; and that our atmosphere must contain, diffused through it, minute portions of the vapours of all those substances with which it is in contact, even down to the earths and metals. I believe that a theory of meteorites has been formed upon this opinion. Perhaps the point has never been distinctly considered; and it may therefore not be uninteresting to urge two or three reasons, in part dependant upon experimental proof, why this should not he the case. The object, therefore, which I shall hold in view in the following pages, is to show that a
limit
exists to the production of vapour of any tension by bodies placed in vacuo, or in elastic media, beneath which limit they are perfectly fixed.
Chlamydia trachomatis OmcB protein is a surface-exposed glycosaminoglycan-dependent adhesin
Authors: Fadel Sanaa , Eley Adrian
Published: December 2006

The OmcB protein of Chlamydia trachomatis is a cysteine-rich outer membrane polypeptide with important functional, structural and antigenic properties. The entire gene encoding the OmcB protein from C. trachomatis serovar LGV1 was cloned and expressed in Escherichia coli and the full-length protein used to raise polyclonal antibodies. Recombinant OmcB was used to show that OmcB is a surface-exposed protein that functions as a chlamydial adhesin. Infectivity inhibition assays carried out using HeLa cells with serovar LGV1 in the presence of purified anti-OmcB serum showed inhibition of infectivity, suggesting that some of the OmcB was surface exposed. Moreover, using recombinant OmcB in infectivity inhibition assays resulted in 70 % inhibition of infectivity, confirming that OmcB plays a role as an adhesin in C. trachomatis. Furthermore, recombinant OmcB protein bound to the surface of HeLa and Hec1B cells, but binding to glycosaminoglycan (GAG)-deficient cells (pgsA-745 and pgsD-677) was markedly reduced, indicating that OmcB binds to GAG-like receptors on host cells.
Intrahost evolution of HBe antigen-negative hepatitis B virus genomes ascribed to the F genotype: a longitudinal 3 year retrospective study
Authors: López José Luis , Mathet Verónica Lidia , Oubiña José Raúl , Campos Rodolfo Héctor
Published: December 2006

The intrahost hepatitis B virus (HBV) genomic evolution process of an HBe antigen (HBeAg)-negative chronic HBV patient (designated RI) was studied. Two nearly full-length direct sequences obtained in 1995 (RI95) and 1998 (RI98) showed: (a) a mutation rate of 2.7×10−3 nucleotides per site per year; (b) nucleotide changes mainly located at single coding regions (P=0.002); (c) mixed populations; and (d) a predominance of non-synonymous substitutions (P=0.0036). Population heterogeneity was assessed by cloning and sequencing of a fragment spanning nearly half the genome. Two-thirds of the analysed clones exhibited long nucleotide deletions. Pairwise genetic diversity revealed that diversity was higher for RI95 than for RI98 cloned sequences. In conclusion, a highly heterogeneous genomic population circulated within patient RI, which might support the persistence of HBV. Finally, the structure of the deletant genomes suggests that they might serve as intermediates for integration to the host-cell genome.
Indeterminate colitis: definition, diagnosis, implications and a plea for nosological sanity
Authors: Martland G T , Shepherd N A
Published: December 2006

In 1978, Price introduced the concept of indeterminate colitis to describe cases in which colonic resections had been undertaken for chronic inflammatory bowel disease (CIBD), but a definitive diagnosis of either of the classical types of CIBD, ulcerative colitis and Crohn's disease, was not possible. This was especially apposite in cases of acute fulminant disease of the colorectum. More recently, the term indeterminate colitis has been applied to biopsy material, when it has not been possible to differentiate between ulcerative colitis and Crohn's disease. In our opinion, and in those of other workers in this field, the term should be restricted to that originally suggested by Price. This then provides a relatively well‐defined group of patients in whom the implications and management of the disease are becoming much clearer. Cases where there are only biopsies with CIBD, but equivocal features for ulcerative colitis and Crohn's disease, should be termed ‘CIBD, unclassified’, ‘equivocal/non‐specific CIBD’ or IBD unclassified (IBDU), in line with recent recommendations. When the diagnosis is correctly restricted to colectomy specimens, there is now good evidence that the majority of cases will behave like ulcerative colitis. Furthermore, the diagnosis should not be a contraindication to subsequent pouch surgery. When the latter is undertaken, surgeons and patients can expect an increased complication rate, compared with classical ulcerative colitis, especially of pelvic sepsis, but most patients fare well. Only very occasional patients, around 10%, will eventually be shown to have Crohn's disease. This review describes the pathology of cases appropriately classified as indeterminate colitis and the implications of that diagnosis. It also highlights recent advances in its pathological features, clinical management and its immunological and genetic associations.
Tumour budding in colorectal carcinoma
Authors: Prall F
Published: December 2006

The term tumour budding denotes that at the invasion front of colorectal adenocarcinomas tumour cells, singly or in small aggregates, become detached from the neoplastic glands. This morphological feature is increasingly being recognized as a strong and robust adverse prognostic factor. Biologically, tumour budding is closely related to the epithelial–mesenchymal transition. In this review the morphological features of tumour budding are discussed, as observed by the surgical pathologist reporting colorectal carcinoma resection specimens. The morphological features are put into context with the rapidly expanding knowledge of the epithelial–mesenchymal transition in general, and the molecular pathology of colorectal carcinoma in particular. Finally, a systematic analysis of the relevant published clinicopathological studies emphasizes the potential of tumour budding as a prognostic factor for routine surgical pathology.
Pathology of non‐infective gastritis
Authors: Srivastava A , Lauwers G Y
Published: December 2006

The discovery of Helicobacter pylori and its intimate role in the development of the most common form of chronic gastritis has elicited a much‐needed interest in non‐neoplastic gastric pathology. This has been paralleled by an increase in upper endoscopic examinations, which allow recognition of novel patterns and distribution of mucosal injury. Numerous attempts at classification have been made, most based on the acuteness or chronicity of gastric mucosal injury. In this review, we will not offer a new classification but present a detailed description of the major clinicopathological entities, based either on the salient morphological features or the underlying aetiologies, i.e. iatrogenic, autoimmune, vascular or idiopathic.
Comparison of two polymer‐based immunohistochemical detection systems: ENVISION+™ and ImmPRESS™
Authors: RAMOS‐VARA JOSÉ A. , MILLER MARGARET A.
Published: December 2006

The non‐specific background reaction produced in avidin–biotin‐based immunohistochemistry, particularly after harsh antigen retrieval procedures, has promoted the use of non‐avidin–biotin systems, yet there are few reports comparing the performance of non‐avidin–biotin, polymer‐based methods. In this study we compare two of these methods, ENVISION+™ and ImmPRESS™, in animal tissues. We examined the immunoreactivity of 18 antigens in formalin‐fixed, paraffin‐embedded tissues. Antigens were located in the cytoplasmic membrane (CD11d, CD18 and CD79a), cytoplasm (calretinin, COX‐1, COX‐2, Glut‐1, HepPar 1, KIT, Melan A, tryptase and uroplakin III) or nucleus (MUM‐1, PGP 9.5 and thyroid transcription factor 1). We also evaluated three infectious agents (Aspergillus, calicivirus and West Nile virus). The staining with ENVISION+™ or ImmPRESS™ was performed simultaneously for each antigen. The intensity of the reaction and background staining were scored. ImmPRESS™ yielded similar or higher reaction intensity than ENVISION+™ in 16/18 antigens. ImmPRESS™ produced abundant background with the other two antigens (calretinin and COX‐2), which hindered interpretation of the specific reaction. The cost of ImmPRESS™ was 25% lower than for ENVISION+™. Based on these results, ImmPRESS™ is a good polymer‐based detection system for routine immunohistochemistry.
Long polymeric tips of atomic force microscopy for large biological samples
Authors: MURAMATSU HIROSHI , YAMAMOTO YUJI , SATO ATSUSHI , ENOMOTO SHIZUO , KIM WOO‐SIK , CHANG SANG‐MOK , KIM JONG MIN
Published: December 2006

We show a new atomic force microscopy technique for obtaining high‐resolution topographic images of large bio‐samples. To obtain high‐resolution topographic images for the samples, we fabricated a long polymeric tip with a small protrusion using two‐photon adsorbed photo‐polymerization techniques. The obtained tip length was over 50 µm, and the tip was used directly to visualize COS‐1 and 293 cells. Compared with commercial tips, the long tip made it easier to obtain topographic images of the large cells. In the magnified topographic images, the sub‐100‐nm resolution was confirmed with the long tips. This long probe tip is expected to broaden large sample‐related studies and applications in the future.
Integration of a scanning ion conductance microscope into phase contrast optics and its application to the quantification of morphological parameters of selected cells
Authors: MANN S. A. , MEYER J. W. , DIETZEL I. D.
Published: December 2006

We have previously described a pulse‐mode scanning ion conductance microscope to investigate membrane surfaces and volume changes of individual cells in culture. We have now developed a miniaturized scanning headstage that enables us to select individual cells for recording under phase contrast optics, considerably improving the selection of individual cells for scanning as well as the positioning of the scanning frames with respect to the position of the cell somata. We show an application in which surfaces and volumes of somata and processes of cultured cells from the central nervous system were quantified separately.
Comparison of skin conductance with entropy during intubation, tetanic stimulation and emergence from general anaesthesia
Authors: Gjerstad A. C. , Storm H. , Hagen R. , Huiku M. , Qvigstad E. , Ræder J.
Published: December 2006

Background:  The number of skin conductance fluctuations (NSCF) expresses sympathetic skin nerve activity. The response entropy (RE) measures electromyographic and electroencephalographic activity in the forehead. The state entropy (SE) measures mainly electroencephalographic activity. When the suppression of frontal muscular activity is complete, RE is equal to SE. RE‐Δ is defined as SE minus RE. The purposes of this study were to examine whether NSCF and RE‐Δ correlate with signs of clinical stress during intubation and tetanic noxious stimulation and to elucidate how rapidly and accurately entropy and NSCF react during emergence from general anaesthesia.

Methods:  Twenty women scheduled for gynaecological laparotomy were studied. During intubation in remifentanil and propofol general anaesthesia, NSCF and RE‐Δ were correlated with the clinical stress score. After a wash‐out period, two series of tetanic stimuli were given, the first with (R+) and the second without (R–) remifentanil infusion. The tetanic pre‐stimuli periods were compared with the tetanic post‐stimuli periods, and R+ was compared with R–. During emergence, the responses of entropy and skin conductance were related to the time of extubation.

Results:  NSCF correlated well with the clinical stress score during intubation (r2= 0.73, P < 0.0005). RE‐Δ showed a weaker correlation (r2= 0.33, P= 0.007). During tetanic stimuli, the NSCF pre‐stimuli level was lower than the post‐stimuli level (P < 0.001), and the NSCF R+ response was lower than the NSCF R– response (P= 0.002). RE‐Δ did not show similar differences. During emergence, RE reacted before NSCF and SE (P= 0.003).

Conclusion:  NSCF was better than RE‐Δ for the measurement of clinical stress during intubation, and was sensitive to tetanic stimuli at different opioid analgesic levels, by contrast with RE‐Δ. Both modalities were able to predict emergence at the end of anaesthesia, but RE was more rapid.
Hemodynamic effect of sustained pulmonary hyperinflation in patients after cardiac surgery: open vs. closed chest
Authors: Nielsen J. , Nygård E. , Kjærgaard J. , Tingleff J. , Larsson A.
Published: December 2006

Background:  In a previous study, we showed that sustained pulmonary hyperinflation, i.e. a lung recruitment maneuver, after closure of the chest in patients undergoing cardiac surgery had significantly negative effects on the central hemodynamics. As elevated pleural pressure is believed to be a major cause of this cardiovascular impairment, we hypothesized that performing the sustained pulmonary hyperinflation under open chest conditions would affect the circulation less.

Methods:  Patients undergoing cardiac by‐pass surgery were included and sustained pulmonary hyperinflations (40 cmH2O airway pressure for 15 s) were performed immediately before and after closure of the sternum. Pulse contour cardiac output, heart rate, mean arterial pressure and pulse pressure variation were measured before, during and 1 min after the hyperinflations. Left ventricular dimensions were measured using trans‐esophageal echocardiography.

Results:  Cardiac output (CO) and mean arterial blood pressure (MAP) decreased significantly during the sustained pulmonary hyperinflation both with an open and closed chest (in parenthesis): CO by 50 (45)% and MAP by 19 (24)%. The left ventricular end‐diastolic area was significantly reduced by 24 (33)%. One minute after the hyperinflation, all measured variables had returned to baseline values. No significant differences in the measured variables were found between the two conditions before, during or 1 min after the hyperinflation.

Conclusion:  Contrary to our hypothesis, sustained pulmonary hyperinflations with the chest open, i.e. before sternal closure, had similar negative effects on central hemodynamics as those performed with the chest closed, i.e. after sternal closure.
Oligosaccharide synthesis regulates gut osmolality in the ant‐attended aphid Metopeurum fuscoviride but not in the unattended aphid Macrosiphoniella tanacetaria
Authors: Woodring J. , Wiedemann R. , Völkl W. , Hoffmann K. H.
Published: December 2006

Abstract:  An artificial phloem sap (APS) for Metopeurum fuscoviride and Macrosiphoniella tanacetaria, based on analysis of their host plant, Tanacetum vulgare, phloem sap, contained 308 μg/μl (900 μmol/μl) sucrose (and no other sugars) and a mixture of 14 amino acids with a total concentration of 82.5 nmol/μl. There was no significant difference in the total amino acid concentration of the honeydew of adult M. fuscoviride fed on the host plant and aphids fed on APS. Incubation of isolated guts in APS indicated no role of gut bacteria or gut enzymes on the amino acid pattern in the gut. The sugar composition of the honeydew of the ant‐attended M. fuscoviride indicated a rapid digestion of sucrose into glucose and fructose, and the simultaneous synthesis of considerable amounts of melezitose and some trehalose. The sugar composition of the honeydew of the unattended M. tanacetaria in contrast showed only traces of trehalose and melezitose, but up to 20% erlose in plant‐fed aphids. Incubation of isolated guts of M. fuscoviride in APS demonstrated a steady high rate of melezitose synthesis by gut enzymes over an 8‐h period. Incubation of isolated guts of M. tanacetaria on the other hand demonstrated only a moderate rate of erlose synthesis and no detectable melezitose or trehalose. Melezitose in the aphid M. fuscoviride is a signal sugar for ants (ecological function), indicating the presence of abundant sugar rich honeydew [Woodring et al. (2004)Physiol. Entomol., vol. 29, pp. 311–319]. It was estimated that melezitose reduces the gut osmolality of M. fuscoviride to approximately 25–35% of what it would be without the synthetases (physiological function). M. tanacetaria on the other hand produces very little honeydew, is not attended by ants, and thus there is little need to synthesize large amounts of oligosaccharides to attract ants or for osmoregulation.
The tree crown distribution of hemlock woolly adelgid, Adelges tsugae (Hem., Adelgidae) from randomized branch sampling
Authors: Evans A. M. , Gregoire T. G.
Published: December 2006

Abstract:  An exotic insect, the hemlock woolly adelgid, Adelges tsugae Annand (Hem., Adelgidae), is spreading through eastern North America, killing hemlock trees [Tsuga canadensis (L.) Carrière], and thereby impoverishing ecosystems. Adelges tsugae, like many alien invasive insects, is difficult to monitor or sample in the forest. Monitoring of A. tsugae has been hampered by lack of information about its distribution within tree crowns. In order to assist future monitoring and biocontrol of A. tsugae, this study investigates the crown distribution of A. tsugae by sampling from the entire height of mature hemlock trees in a forest with an established infestation. In addition to A. tsugae, sampling includes scale insects, which are another group of important pests on hemlock trees. This study demonstrates the utility of a randomized branch sampling (RBS) plan for monitoring both invasive insects as well as native insects that are difficult to sample. Results from the RBS show that in trees with high populations of A. tsugae, branches from the lower crown have slightly higher densities of A. tsugae than upper crown branches. In trees with low A. tsugae populations, the upper crown may have higher A. tsugae densities than the lower crown. North pointing branches also have higher densities of A. tsugae than branches pointing in other cardinal directions. Future sampling efforts for A. tsugae can take advantage of higher densities in certain portions of the crown to increase accuracy.
Opportunism of Conidiobolus obscurus stems from depression of infection in situ to progeny colonies of host alatae as disseminators of the aphid‐pathogenic fungus
Authors: Zhang Guo‐Zhong , Feng Ming‐Guang , Chen Chun , Ying Sheng‐Hua
Published: December 2006

Conidiobolus (Entomophthorales: Ancylistaceae) includes common aphid pathogens but causes sporadic mycosis worldwide. This epizootiological opportunism was explored herein by examining the potential of mycosis transmission in the progeny colonies of 513 Myzus persicae alates as disseminators of C. obscurus often infecting aphids. The alates exposed to spore showers were flown for 2.05 (0.01–8.95) km on flight mills and then reared individually on cabbage at 20–23°C for 14 day colonization. All truly infected alates were mycosed within 6 days and averagely left 3.9 (0–15) nymphs while those uninfected produced 11.6 (0–35) nymphs during the same period. Secondary and tertiary infections occurred only in 16.2% and 4.8% of the progeny colonies of the mycosed alates respectively, due to c. 60% of the cadavers forming resting spores. Most of the contagious infections appeared on days 4–8 after colonization and no more occurred from day 11 onwards. Trends of colony sizes (last‐day averaging 51.5 aphids) and mycosis transmission (sixth‐day maximum 6.3%) fit well to logistic (r 2 = 0.99) and Gompertz growth models (r 2 = 0.91) respectively. The results confirm that the opportunism of C. obscurus stems from depression of contagious infection after dissemination by host alates and suggest that it be overwhelmed by the prevalence of other non‐resting fungal species.
A LOCATION MODEL WITH PREFERENCE FOR VARIETY*
Authors: KIM HYUNHO , SERFES KONSTANTINOS
Published: December 2006

We propose a new location model where consumers are allowed to make multiple purchases (i.e., one unit from each firm). This model may fit many markets (e.g. newspapers, credit cards) better than existing models. A common feature of these markets is that some consumers are loyal to one brand, while others consume more than one product. Our model yields predictions consistent with this observation. If firms are allowed to choose their locations on the interval, then spatial differentiation may not be maximal and in some cases it may even be minimal. Thus, under certain conditions, we restore Hotelling's Principle of Minimum Differentiation.
THEORY AND CALIBRATION OF SWAP MARKET MODELS
Authors: Galluccio S. , Ly J.‐M. , Huang Z. , Scaillet O.
Published: December 2006

This paper introduces a general framework for market models, named Market Model Approach, through the concept of admissible sets of forward swap rates spanning a given tenor structure. We relate this concept to results in graph theory by showing that a set is admissible if and only if the associated graph is a tree. This connection enables us to enumerate all admissible models for a given tenor structure. Three main classes are identified within this framework and correspond to the co‐terminal, co‐initial, and co‐sliding model. We prove that the LIBOR market model is the only admissible model of a co‐sliding type. By focusing on the co‐terminal model in a lognormal setting, we develop and compare several approximating analytical formulae for caplets, while swaptions can be priced by a simple Black‐type formula. A novel calibration technique is introduced to allow simultaneous calibration to caplet and swaption prices. Empirical calibration of the co‐terminal model is shown to be faster, more robust, and more efficient than the same procedure applied to the LIBOR market model. We then argue that the co‐terminal approach is the simplest and most convenient market model for pricing and hedging a large variety of exotic interest‐rate derivatives.
MONOTONICITY PROPERTIES OF OPTIMAL INVESTMENT STRATEGIES FOR LOG‐BROWNIAN ASSET PRICES
Authors: Borell Christer
Published: December 2006

Consider the geometric Brownian motion market model and an investor who strives to maximize expected utility from terminal wealth. If the investor's relative risk aversion is an increasing function of wealth, the main result in this paper proves that the optimal demand in terms of the total wealth invested in a given risky portfolio at any date is decreasing in absolute value with wealth. The proof depends on the functional form of the Brunn–Minkowski inequality due to Prékopa.
Post‐ischaemic treatment with the cyclooxygenase‐2 inhibitor nimesulide reduces blood–brain barrier disruption and leukocyte infiltration following transient focal cerebral ischaemia in rats
Authors: Candelario‐Jalil Eduardo , González‐Falcón Armando , García‐Cabrera Michel , León Olga Sonia , Fiebich Bernd L.
Published: December 2006

Several studies suggest that cyclooxygenase (COX)‐2 plays a pivotal role in the progression of ischaemic brain damage. In the present study, we investigated the effects of selective inhibition of COX‐2 with nimesulide (12 mg/kg) and selective inhibition of COX‐1 with valeryl salicylate (VAS, 12–120 mg/kg) on prostaglandin E2(PGE2) levels, myeloperoxidase (MPO) activity, Evans blue (EB) extravasation and infarct volume in a standardized model of transient focal cerebral ischaemia in the rat. Post‐ischaemic treatment with nimesulide markedly reduced the increase in PGE2levels in the ischaemic cerebral cortex 24 h after stroke and diminished infarct size by 48% with respect to vehicle‐treated animals after 3 days of reperfusion. Furthermore, nimesulide significantly attenuated the blood–brain barrier (BBB) damage and leukocyte infiltration (as measured by EB leakage and MPO activity, respectively) seen at 48 h after the initial ischaemic episode. These studies provide the first experimental evidence that COX‐2 inhibition with nimesulide is able to limit BBB disruption and leukocyte infiltration following transient focal cerebral ischaemia. Neuroprotection afforded by nimesulide is observed even when the treatment is delayed until 6 h after the onset of ischaemia, confirming a wide therapeutic window of COX‐2 inhibitors in experimental stroke. On the contrary, selective inhibition of COX‐1 with VAS had no significant effect on the evaluated parameters. These data suggest that COX‐2 activity, but not COX‐1 activity, contributes to the progression of focal ischaemic brain injury, and that the beneficial effects observed with non‐selective COX inhibitors are probably associated to COX‐2 rather than to COX‐1 inhibition.
Effect of Chronic Ethanol Consumption on the Response of Parathyroid Hormone to Hypocalcemia in the Pregnant Rat
Authors: Duggal Shalu , Simpson Mary Elizabeth , Keiver Kathy
Published: December 2006

Background: Chronic alcohol (ethanol) consumption during pregnancy results in maternal/fetal hypocalcemia, which may underlie some of ethanol's adverse effects on maternal and fetal bone, and fetal/neonatal health. Ethanol appears to alter the relationship between parathyroid hormone (PTH) and blood calcium (Ca) level, and PTH does not increase in response to ethanol‐induced hypocalcemia. However, it is not known whether ethanol actually prevents PTH from responding, or whether the ability to regulate blood Ca is intact, but ethanol lowers the level of Ca maintained. The objective of this study was to determine whether chronic ethanol consumption impairs the ability of the pregnant female to increase PTH in response to acute hypocalcemia.

Methods: Rats were fed isocaloric diets with ethanol (36% ethanol‐derived calories, E group) or without ethanol [pair‐fed (PF) and control (C) groups], before and throughout 21 days of gestation. On day 21 gestation, rats received an intraperitoneal injection of ethylene glycol‐bis (β‐aminoethyl ether)‐N,N,N′,N′‐tetraacetic acid (EGTA) (300 or 500 μmol/kg body weight) or saline (saline group), or no injection (baseline group). Blood was collected from the baseline group, and at 30 or 60 minutes postinjection (saline and EGTA groups), and analyzed for ionized Ca (iCa), pH, and PTH.

Results: Consistent with previous studies, ethanol consumption decreased blood iCa levels at baseline, but PTH levels did not differ among groups. Administration of EGTA significantly decreased blood iCa levels by 30 minutes, but ethanol did not prevent PTH from increasing in response to the hypocalcemia. In all diet groups, PTH levels were significantly increased by 30 minutes. Ethanol did, however, appear to decrease the maximum PTH level achievable in blood.

Conclusions: These data suggest that chronic ethanol consumption does not impair the ability of the pregnant rat to raise serum PTH levels in response to acute hypocalcemia, but ethanol's effect on maximal PTH secretion could impair the ability of the pregnant female to sustain high PTH levels in response to chronic hypocalcemia.
Development of Naltrexone Supersensitivity During Food‐Maintained Responding Enhances Naltrexone's Ability to Reduce Ethanol‐Maintained Responding
Authors: Williams Keith L.
Published: December 2006

Background:Similar doses of the opiate antagonist naltrexone (NTX) reduce responding maintained by food and ethanol. In animals responding for food, repeated administration of NTX produces supersensitivity to NTX. The purpose of this study was to determine whether the factors that produce enhanced sensitivity to NTX during food‐maintained responding also contribute to NTX's abililty to reduce ethanol‐maintained responding.

Methods:Rats (n=12) were trained to lever press using food reinforcement. After responding stabilized, the rats were trained to respond for 10% ethanol. Before ethanol sessions, injections of 30 mg/kg NTX were given. Subsequently, weekly cumulative NTX dose–effect curves (1, 3, 10, 30, and 100 mg/kg), known to produce NTX supersensitivity, were determined during food‐maintained responding in half the rats for 8 weeks while the other half of the rats received saline vehicle injections instead. To determine whether NTX supersensitivity would transfer to ethanol self‐administration, ethanol‐maintained responding was re‐established and 30 mg/kg NTX was administered again.

Results:Initially, 30 mg/kg NTX had little effect on ethanol‐maintained responding. During food‐maintained responding, supersensitivity developed in rats receiving weekly cumulative NTX injections. After development of supersensitivity, 30 mg/kg decreased ethanol‐maintained responding. Naltrexone's potency to reduce ethanol‐maintained responding was unchanged in rats that received only vehicle injections for 8 weeks.

Conclusion:The mechanisms that produce NTX supersensitivity during food‐maintained responding may play a role in NTX's effect on ethanol consumption. Naltrexone's effect on responding for ethanol was much smaller than that reported in other studies. Further exploration may lead to techniques that maximize NTX's effect on ethanol while minimizing its effect on other behaviors.
The Effect of IT and Co‐location on Knowledge Dissemination
Authors: Song Michael , Berends Hans , Van Der Bij Hans , Weggeman Mathieu
Published: December 2006

Due to the increasing globalization of businesses, new ideas for innovation need to be disseminated rapidly both within and across different departments and divisions. Frequently, ideas and information are dispersed over globally distributed organizations or team members. As a result, the exchange of knowledge has become not only very important for innovation but also highly complex. To facilitate this knowledge exchange, electronically mediated interactions are growing rapidly, replacing traditional face‐to‐face communications. However, literature provides contradicting results regarding the effectiveness of computer‐mediated communication (CMC) versus face‐to‐face communication. This study attempts to reconcile differences in the literature on the benefits of CMC technologies and co‐location. Focusing on knowledge dissemination in technology development processes in high‐technology firms, the study investigates the relative impact of CMC technologies and co‐location of research and development (R&D) staff, as well as the mutual interaction between them. The present article hypothesizes that CMC technologies and co‐location of R&D staff have a positive impact on knowledge dissemination. Further, it is hypothesized that it is more favorable to co‐locate R&D staff than to invest in CMC technologies and that the effects of co‐location and CMC interact negatively. These hypotheses are tested using empirical data collected from 277 high‐technology firms in the United States, and the results are generalized by conducting the same test on data from 125 high‐technology firms in the Netherlands. Tests are conducted in a real‐world setting, differing from previous comparative studies that mainly used laboratory experiments. Empirical results support the main effects of CMC technologies and co‐location of R&D staff on knowledge dissemination. Other empirical results contradict conventional wisdom. Investing in CMC technologies is found to be favorable over co‐locating R&D staff for knowledge dissemination. Moreover, the two communication channels strengthen each other. The discussion section presents the contours of a firm‐level theory on communication infrastructures and knowledge dissemination, focusing on the scope and the heterogeneity of knowledge dissemination, which may explain these initially surprising results. From the arguments it follows that the choice for investment in co‐location or CMC technologies depends on the scope of knowledge dissemination that has to be facilitated. Furthermore, the conclusion is made that effective knowledge dissemination requires a balanced investment in co‐location and information technologies to be able to deal with the heterogeneous but interdependent types of knowledge dissemination.
Dealing with Darwin: How Great Companies Innovate at Every Phase of Their Evolution by Geoffrey A. Moore
Authors: Deck Mark J.
Published: December 2006

Books reviewed in this issue:

Dealing with Darwin: How Great Companies Innovate at Every Phase of Their Evolution

Accelerated Product Development: Combining Lean and Six Sigma for Peak Performance

Fast Innovation: Achieving Superior Differentiation, Speed to Market, and Increased Profitability

Projects at Warp‐Speed with Q
R
PD: The Definitive Guidebook to Quality Rapid Product Development

Working Virtually: Challenges of Virtual Teams

Management of Technology: Managing Effectively in Technology‐Intensive Organizations
Efficacies of caspofungin and a combination of caspofungin and meropenem in the treatment of murine disseminated candidiasis
Authors: OZCAN SEMA KECELI , BUDAK FATMA , WILLKE AYSE , FILIZ SERDAR , COSTUR PELIN , DALCIK HAKKI
Published: December 2006

Disseminated candidiasis is relatively common in immunocompromised patients. The treatment protocol of these patients usually includes broad‐spectrum antibiotics and also emprical antifungals initiated due to unresponsiveness to antibiotics. In this study the efficacies of caspofungin and meropenem – separately and together – in mice with disseminated candidiasis were studied. Immunocompetent mice were infected intravenously with 2×106 CFU of Candida albicans. At 24 h postinfection, intraperitoneal therapy was initiated and was continued for 7 days. Therapy groups included those given caspofungin (0.5, 1.25, 5 mg/kg/day), meropenem (20 mg/kg/day), and a combination of the two drugs. The outcome of therapy was evaluated by kidney tissue burden studies and histologic examination. In vitro, drug susceptibilities were tested by checkerboard analysis. Kidney CFU counts showed that mice that had received both drugs had lower residual burdens. Caspofungin was effective at doses of 0.5, 1.25, 5 mg/kg compared to infected untreated controls. In vitro, MICs of caspofungin and meropenem were <0.075 μg/ml and >64 μg/ml, respectively. Synergism was observed with the combination. Histopathology showed that the degree of inflammation was 25% less and tubular necrosis was more restricted in combined therapy than monotherapy. The results indicate that concurrent caspofungin and meropenem therapy may be beneficial
Pyrosequencing of the DNA gyrase gene in Neisseria species: effective indicator of ciprofloxacin resistance in Neisseria gonorrhoeae
Authors: LINDBÄCK EMMA , UNEMO MAGNUS , AKHRAS MICHAEL , GHARIZADEH BABACK , FREDLUND HANS , POURMAND NADER , WRETLIND BENGT
Published: December 2006

The quinolone resistance determining region (QRDR) of the gyrA gene in ciprofloxacin‐susceptible strains (n=53) and strains of Neisseria spp. with reduced susceptibility (n=70) was determined by the pyrosequencing method. Results showed that the QRDR of the gyrA gene is an effective molecular indicator of resistance to ciprofloxacin in Neisseria gonorrhoeae, and presumably in Neisseria meningitidis, but not in all other Neisseria spp. This sequence was not unique for N. gonorrhoeae and seems unsuitable for species verification of N. gonorrhoeae. However, whether it is also possible to use this region for verification depends on the specificity of the primary screening method used.
Merkel cell carcinoma frequently shows histologic features of basal cell carcinoma: a study of 30 cases
Authors: Ball Nigel J. , Tanhuanco‐Kho Grace
Published: December 2006

Background:  Merkel cell carcinoma (MCC) is a basaloid cutaneous neoplasm that may be mistaken for basal cell carcinoma (BCC).

Methods:  Thirty MCCs were examined for areas that histologically resembled BCC.

Results:  One of the histologic features of BCC (either a mucinous stroma or stromal artifactual retraction) was identified in all MCCs. A mucinous stroma was found in 28 MCCs (93%), stromal artifactual retraction in 27 (90%), mucin‐containing gland‐like spaces within tumor nests in 8 (27%), focal peripheral palisading in 8 (27%), epidermal involvement in 3 (10%) and dystrophic calcification in 1 MCC (3%). The cytologic features and absence of widespread peripheral palisading were the most reliable discriminators between MCC and BCC on routine sections. Squamous cell carcinoma was identified in four cases (13%). Two cases (7%) contained pagetoid intraepidermal spread (IES) of MCC. In one case, there was IES over the entire epidermal surface associated with intranuclear clearing, resembling the intranuclear cytoplasmic inclusions (INI) common in melanocytic tumors. INI were identified in six MCCs (20%).

Conclusions:  MCCs frequently contain areas that histologically resemble BCC and other more common cutaneous malignancies. This can lead to diagnostic errors, particularly in small fragmented curettage specimens or frozen sections.
A case of cutaneous myoepithelial carcinoma
Authors: Tanahashi Jin , Kashima Kenji , Daa Tsutomu , Kondo Yoshiyuki , Kuratomi Eiji , Yokoyama Shigeo
Published: December 2006

Background:  Cutaneous myoepithelioma, both benign and malignant, is a rare neoplasm composed of neoplastic myoepithelial cells showing diverse histopathological features, and criteria for discriminating benign or malignant have not been fully clarified.

Patient:  We present a case of cutaneous myoepithelial carcinoma in a 62‐year‐old woman presenting a solid mass in the right back.

Results:  Resected tumor was located in the whole dermis and subcutis. Histopathologically, two different growth patterns were noted: a small‐nested or trabecular pattern in the superficial part and a large nodular pattern with extensive central necrosis in the deep part. Tumor cells were all epithelioid, although plasmacytoid and glycogen‐rich clear cells were also observed within the large nodules of the deep part. Immunohistochemically, the cells were positive for both epithelial and myogenic markers, suggesting myoepithelial origin. Lymphatic invasion and lymph node metastasis were evident despite inconspicuous atypia and low mitotic rate.

Conclusion:  The final diagnosis was cutaneous myoepithelial carcinoma. At present, it seems to be difficult to predict the behavior of myoepithelioma of the skin and soft tissue, although atypia and high mitotic rate are reported to be associated with local recurrence and metastasis.
Characteristics of dermatologists who read dermatopathology slides
Authors: Brauer Jeremy A. , Shin Daniel B. , Troxel Andrea B. , Shapiro Michael , Levy Ross M. , Ming Michael E.
Published: December 2006

Background:  The characteristics and prevalence of dermatologists reading dermatopathology slides are not well understood.

Methods:  We surveyed 1406 members of the American Academy of Dermatology (AAD), including all 497 who were also members of the American Society of Dermatopathology (ASDP) along with a random sample of the remaining AAD members who were not ASDP members. Seven hundred and thirty of 1406 (51.9%) responded with a usable survey. Logistic regression was used to analyze responses by ASDP member dermatologists, non‐ASDP member dermatologists and in a weighted analysis for dermatologists as a whole.

Results:  A total of 32.7% of dermatologists as a whole generated at least one final microscopic diagnosis in the preceding year. Multivariate analysis demonstrated that men were significantly more likely to read dermatopathology slides (odds ratio (OR) = 1.90; 95% confidence interval (CI) 1.16–3.12; p = 0.01). Additionally, there was significant variation by region (p < 0.001); compared with dermatologists in the Midwest, dermatologists in the Southeast (OR = 0.39; 95% CI 0.19–0.80) were significantly less likely to read slides, while those in the Mountain (OR = 3.09; 95% CI 1.10–8.72) and West (OR = 2.01; 95% CI 1.04–3.90) regions were significantly more likely. There were no significant associations found between reading slides and the year of residency completion, the number of patients seen per week or being primarily in academics.

Conclusions:  The practice of dermatologists reading dermatopathology slides is relatively common, with significant regional and sex differences.
The equinatoxin N‐terminus is transferred across planar lipid membranes and helps to stabilize the transmembrane pore
Authors: Kristan Katarina , Viero Gabriella , Mac̆ek Peter , Dalla Serra Mauro , Anderluh Gregor
Published: December 2006

Equinatoxin II is a cytolytic protein isolated from the sea anemone Actinia equina. It is a member of the actinoporins, a family of eukaryotic pore‐forming toxins with a unique mechanism of pore formation. Equinatoxin II is a 20 kDa cysteineless protein, with sphingomyelin‐dependent activity. Recent studies showed that the N‐terminal region of the molecule requires conformational flexibility during pore formation. An understanding of the N‐terminal position in the final pore and its role in membrane insertion and pore stability is essential to define the precise molecular mechanism of pore formation. The formation of pores and their electrophysiologic characteristics were studied with planar lipid membranes. We show that amino acids at positions 1 and 3 of equinatoxin II are exposed to the lumen of the pore. Moreover, sulfhydryl reagents and a hexa‐histidine tag attached to the N‐terminus revealed that the N‐terminus of the toxin extends through the pore to the other (trans) side of the membrane and that negatively charged residues inside the pore are crucial to define the electrophysiologic characteristics of the channel. Finally, we detected a new, less stable, state with a lower conductance by using a deletion mutant in which the first five N‐terminal amino acids were removed. We propose that the first five amino acids help to anchor the amphipathic helix on the trans side of the membrane and consequently stabilize the final transmembrane pore.