bluuebunny/crossref_metadata_2025 huggingface dataset:
Not All Secretory Granules Are Created Equal: Partitioning of Soluble Content Proteins
Authors: Sobota Jacqueline A. , Ferraro Francesco , Bäck Nils , Eipper Betty A. , Mains Richard E.
Published: September 2006

Secretory granules carrying fluorescent cargo proteins are widely used to study granule biogenesis, maturation, and regulated exocytosis. We fused the soluble secretory protein peptidylglycine α-hydroxylating monooxygenase (PHM) to green fluorescent protein (GFP) to study granule formation. When expressed in AtT-20 or GH3 cells, the PHM-GFP fusion protein partitioned from endogenous hormone (adrenocorticotropic hormone, growth hormone) into separate secretory granule pools. Both exogenous and endogenous granule proteins were stored and released in response to secretagogue. Importantly, we found that segregation of content proteins is not an artifact of overexpression nor peculiar to GFP-tagged proteins. Neither luminal acidification nor cholesterol-rich membrane microdomains play essential roles in soluble content protein segregation. Our data suggest that intrinsic biophysical properties of cargo proteins govern their differential sorting, with segregation occurring during the process of granule maturation. Proteins that can self-aggregate are likely to partition into separate granules, which can accommodate only a few thousand copies of any content protein; proteins that lack tertiary structure are more likely to distribute homogeneously into secretory granules. Therefore, a simple “self-aggregation default” theory may explain the little acknowledged, but commonly observed, tendency for both naturally occurring and exogenous content proteins to segregate from each other into distinct secretory granules.
Rho2 Is a Target of the Farnesyltransferase Cpp1 and Acts Upstream of Pmk1 Mitogen-activated Protein Kinase Signaling in Fission Yeast
Authors: Ma Yan , Kuno Takayoshi , Kita Ayako , Asayama Yuta , Sugiura Reiko
Published: September 2006

We have previously demonstrated that knockout of the calcineurin gene or inhibition of calcineurin activity by immunosuppressants resulted in hypersensitivity to Cl−in fission yeast. We also demonstrated that knockout of the components of the Pmk1 mitogen-activated protein kinase (MAPK) pathway, such as Pmk1 or Pek1 complemented the hypersensitivity to Cl−. Using this interaction between calcineurin and Pmk1 MAPK, here we developed a genetic screen that aims to identify new regulators of the Pmk1 signaling and isolated vic (viable in the presence of immunosuppressant and chloride ion) mutants. One of the mutants, vic1-1, carried a missense mutation in the cpp1+gene encoding a β subunit of the protein farnesyltransferase, which caused an amino acid substitution of aspartate 155 of Cpp1 to asparagine (Cpp1D155N). Analysis of the mutant strain revealed that Rho2 is a novel target of Cpp1. Moreover, Cpp1 and Rho2 act upstream of Pck2–Pmk1 MAPK signaling pathway, thereby resulting in the vic phenotype upon their mutations. Interestingly, compared with other substrates of Cpp1, defects of Rho2 function were more phenotypically manifested by the Cpp1D155Nmutation. Together, our results demonstrate that Cpp1 is a key component of the Pck2–Pmk1 signaling through the spatial control of the small GTPase Rho2.
Ketanserin Pretreatment Reverses Alfentanil-induced Muscle Rigidity
Authors: Weinger Matthew B. , Cline Elizabeth J. , Smith N. Ty , Koob George F.
Published: September 2006

Systemic pretreatment with hetanserin, a relatively specific type-2 serotonin receptor antagonist, significantly attenuated the muscle rigidity produced in rats by the potent short-acting oplate agonist alfentanil. Following placement of subcutaneous electrodes in each animal's left gastrocnemius muscle, rigidity was assessed by analyzing root-mean-square electromyographic activity. Intraperitoneal ketanserin administration at doses of 0.63 and 2.5 mg/kg prevented the alfentanil-induced increase in electromyographic activity compared with animals pretreated with saline. Chlordiazepoxide at doses up to 10 mg/kg failed to significantly influence the rigidity produced by alfentanil. Despite the absence of rigidity, animals that received ketanserin (greater than 0.31 mg/kg i.p.) followed by alfentanil were motionless, flaccid, and less responsive to external stimuli than were animals receiving alfentanil alone. Rats that received ketanserin and alfentanil exhibited less rearing and exploratory behavior at the end of the 60-min recording period than did animals that received ketanserin alone. These results, in combination with previous work, suggest that muscle rigidity, a clinically relevant side-effect of parenteral narcotic administration, may be partly mediated via serotonergic pathways. Pretreatment with type-2 serotonin antagonists may be clinically useful in attenuating opiate-induced rigidity, although further studies will be necessary to assess the interaction of possibly enhanced CNS, cardiovascular, and respiratory depression.
The Effect of Volatile Anesthetics on the pH Dependence of Calcium Uptake by Cardiac Sarcoplasmic Reticulum
Authors: Casella Eugenie Shalhoub , Suite Nicholas D. A. , Fisher Yvonne I. , Blanck Thomas J. J.
Published: September 2006

The effect of volatile anesthetics (VA) on the pH dependence of calcium uptake by cardiac sarcoplasmic reticulum (SR) was studied. SR was incubated at 37°C with 45CaCl2 in the control state (no anesthetic) and in the presence of each of the VA from pH 6.6–7.6. The VA used were: halothane, 1.3%; enflurane, 1.8%; and isoflurane, 1.2%. In the control state, the initial rate of calcium uptake, measured after a 2-min incubation, was maximal at pH 6.8 (mean ± SEM:665 ± 37 nmoles/mg) and markedly inhibited at pH 7.6 (107 ± 9 nmoles/mg). In the presence of the VA, the calcium uptake rate was mildly depressed (7–32%) at pH 6.6–6.8, unchanged at pH 7.0, and greatly enhanced (52–78%) at pH 7.2–7.6, when compared to control. The maximal uptake of calcium by the SR at a calcium concentration of 10−6M, measured by a 20-min incubation, had a similar pH dependence in the control state, with a decline first evident at pH 7.2 and a 50% drop in the maximal uptake of calcium from pH 7.0–7.6. The presence of the VA was associated with a uniform depression of the maximal uptake of calcium by the SR at all pH levels measured. In view of these findings, it appears that pH does affect SR function in the presence of VA. This alteration of the pH effect by VA may be a factor responsible for discrepancies in results previously reported by investigators studying the effects of VA on the uptake of calcium by the SR.
Candida albicans HWP1 gene expression and host antibody responses in colonization and disease
Authors: Naglik Julian R. , Fostira Florentia , Ruprai Jasmeet , Staab Janet F. , Challacombe Stephen J. , Sundstrom Paula
Published: September 2006

In vivoexpression of the developmentally regulatedCandida albicanshyphal wall protein 1 (HWP1) gene was analysed in human subjects who were culture positive forC. albicansand had oral symptoms (n=40) or were asymptomatic (n=29), or had vaginal symptoms (n=40) or were asymptomatic (n=29).HWP1mRNA was present regardless of symptoms, implicating hyphal and possibly pseudohyphal forms in mucosal carriage as well as disease. As expected, in control subjects without oral symptoms (n=10) and without vaginal symptoms (n=10) who were culture negative in oral and vaginal samples,HWP1mRNA was not detected. However, exposure to Hwp1 in healthy culture-negative controls, as well as in oral candidiasis and asymptomatic mucosal infections, was shown by the existence of local salivary and systemic adaptive antibody responses to Hwp1. The results are consistent with a role for Hwp1 in gastrointestinal colonization as well as in mucosal symptomatic and asymptomatic infections. Overall, Hwp1 and hyphal growth forms appear to be important factors in benign and invasive interactions ofC. albicanswith human hosts.
The origami of thioredoxin‐like folds
Authors: Pan Jonathan L. , Bardwell James C.A.
Published: September 2006

Origami is the Japanese art of folding a piece of paper into complex shapes and forms. Much like origami of paper, Nature has used conserved protein folds to engineer proteins for a particular task. An example of a protein family, which has been used by Nature numerous times, is the thioredoxin superfamily. Proteins in the thioredoxin superfamily are all structured with a β‐sheet core surrounded with α‐helices, and most contain a canonical CXXC motif. The remarkable feature of these proteins is that the link between them is the fold; however, their reactivity is different for each member due to small variations in this general fold as well as their active site. This review attempts to unravel the minute differences within this protein family, and it also demonstrates the ingenuity of Nature to use a conserved fold to generate a diverse collection of proteins to perform a number of different biochemical tasks.
The MRG domain of human MRG15 uses a shallow hydrophobic pocket to interact with the N‐terminal region of PAM14
Authors: Zhang Peng , Zhao Jingyue , Wang Bing , Du Jiamu , Lu Yongcheng , Chen Jiangye , Ding Jianping
Published: September 2006

MRG15 is a transcription factor expressed in a variety of human tissues, and its orthologs have been found in many other eukaryotes which constitute the MRG protein family. It plays a vital role in embryonic development and cell proliferation, and is involved in cellular senescence. The C‐terminal part of MRG15 forms a conserved MRG domain which is involved in interactions with the tumor suppressor protein retinoblastoma and a nucleoprotein PAM14 during transcriptional regulation. We report here the characterization of the interaction between the MRG domain of human MRG15 and PAM14 using both yeast two‐hybrid and in vitro binding assays based on the crystal structure of the MRG domain. The MRG domain is predominantly hydrophobic, and consists of mainly α‐helices that are arranged in a three‐layer sandwich topology. The hydrophobic core is stabilized by interactions among a number of conserved hydrophobic residues. The molecular surface is largely hydrophobic, but contains a few hydrophilic patches. Structure‐based site‐directed mutagenesis studies identified key residues involved in the binding of PAM14. Structural and biochemical data together demonstrate that the PAM14 binding site is consisted of residues Ile160, Leu168, Val169, Trp172, Tyr235, Val268, and Arg269 of MRG15, which form a shallow hydrophobic pocket to interact with the N‐terminal 50 residues of PAM14 through primarily hydrophobic interactions. These results provide the molecular basis for the interaction between the MRG domain and PAM14, and reveal insights into the potential biological function of MRG15 in transcription regulation and chromatin remodeling.
Detection of early abnormalities in gastric function in first‐degree relatives of patients with pernicious anemia*
Authors: Juncà Jordi , De Soria Paloma López , Granada Maria Luisa , Flores Alonso , Márquez Eugenia
Published: September 2006

Abstract:  Background: Pernicious anemia (PA), as many other autoimmune disorders, has a trend to appear in other members of the family of the affected patients. Although this fact has been recognized since some decades ago, less is known about the frequency with which the abnormalities detected in the patients appear also in their relatives, the correlations that exist among these abnormalities and to what extent these markers of the disease relate to serum cobalamin concentration. Subjects and results: For these reasons we studied the values of some markers of PA in a group of 79 first‐degree relatives and we detected that the most frequent abnormalities are a decrease in serum pepsinogen I (22.7% of cases), an increase in serum gastrin (16.5% of cases) and in parietal cell antibody at a titer ≥40 (23.4% of cases). From a functional point of view, a decrease in hydrogen excretion in a magnesium breath test, indicative of achlorhydria, is also frequent (29.1%). The fall in cobalamin concentration runs in parallel with these abnormalities. The concentration of this vitamin was below normal levels in as much as 15.2% of cases. Conclusion: These findings emphasize the need for searching for the presence of occult or latent PA in relatives of patients with this diagnosis, not only to prevent the development of anemia but also to avoid other undesirable consequences of cobalamin deficiency.
Amrubicin induces apoptosis in human tumor cells mediated by the activation of caspase‐3/7 preceding a loss of mitochondrial membrane potential
Authors: Hanada Mitsuharu , Noguchi Toshihiro , Yamaoka Takashi
Published: September 2006

Amrubicin, a completely synthetic 9‐aminoanthracycline derivative, inhibits cell growth by stabilizing a topoisomerase II–DNA complex. This study was designed to examine the apoptosis induced in human leukemia U937 cells by amrubicin and its active metabolite amrubicinol. Amrubicin, amrubicinol and other antitumor agents, such as daunorubicin and etoposide, induced typical apoptosis with characteristic nuclear morphological change and DNA fragmentation. Measuring the population of sub‐G1 phase cells, it was found that under conditions where cell growth was inhibited by either amrubicin or amrubicinol, U937 cells underwent apoptotic cell death in a dose‐dependent manner accompanied by an arrest of the cell cycle at G2/M. Furthermore, amrubicin‐ and amrubicinol‐induced apoptosis was mediated by the activation of caspase‐3/7, but not caspase‐1, preceding a loss of mitochondrial membrane potential. These results indicate that both a reduction in mitochondrial membrane potential and the activation of caspase‐3/7 are key events in the apoptosis induced by amrubicin and amrubicinol as well as the other antitumor agents. In addition, studies with oligomycin suggested that the apoptosis induced by amrubicin and amrubicinol involved substantially different pathways from that triggered by daunorubicin and etoposide. Oligomycin blocked the etoposide‐induced increase in the number of sub‐G1 phase cells without preventing the activation of caspase‐3/7, and had no inhibitory effect on the expansion of the sub‐G1 population in daunorubicin‐treated cells, whereas apoptosis‐related changes caused by amrubicin and amrubicinol were suppressed in the presence of oligomycin. (Cancer Sci 2006; 97: 1396–1403)
Mandibles and molars of the wood mouse, Apodemus sylvaticus (L.): integrated latitudinal pattern and mosaic insular evolution
Authors: Renaud Sabrina , Michaux Johan R.
Published: September 2006

Aim  The distinct nature of island populations has traditionally been attributed either to adaptation to particular insular conditions or to random genetic effects. In order to assess the relative importance of these two disparate processes, insular effects were addressed in the European wood mouse, Apodemus sylvaticus (Linnaeus, 1758).

Location  Wood mice from 33 localities on both mainland and various Atlantic and western Mediterranean islands were considered. This sampling covers only part of the latitudinal range of A. sylvaticus but included the two main genetic clades identified by previous studies. Islands encompass a range of geographical conditions (e.g. small islands fringing the continent through large and isolated ones).

Methods  The insular syndrome primarily invokes variations in body size, but ecological factors such as release from competition, niche widening and food availability should also influence other characters related to diet. In the present study, the morphology of the wood mice was quantified based on two characters involved in feeding: the size and shape of the mandibles and first upper molars. The size of the mandible is also a proxy for the body size of the animal. Patterns of morphological differentiation of both features were estimated using two‐dimensional outline analysis based on Fourier methods.

Results  Significant differences between mainland and island populations were observed in most cases for both the mandibles and molars. However, molars and mandibles displayed divergent patterns. Mandible shape diverged mostly on islands of intermediate remoteness and competition levels, whereas molars exhibited the greatest shape differentiation on small islands, such as Port‐Cros and Porquerolles. A mosaic pattern was also displayed for size. Body and mandible size increased on Ibiza, but molar size remained similar to mainland populations. Mosaic patterns were, however, not apparent in the mainland populations. Congruent latitudinal variations were evident for the size and shape of both mandibles and molars.

Main conclusions  Mosaic evolution appears to characterize insular divergence. The molar seems to be more prone to change with reduced population size on small islands, whereas the mandible could be more sensitive to peculiar environmental conditions on large and remote islands.
Different susceptibilities of spontaneous rhythmicity and myogenic contractility to intestinal muscularis inflammation in the hapten‐induced colitis
Authors: Kiyosue M. , Fujisawa M. , Kinoshita K. , Hori M. , Ozaki H.
Published: September 2006

Abstract  We examined the time‐dependent changes in the immunoreactivity of the smooth muscle region and the accompanying motility disorder in a hapten‐induced rat model of colitis. Histological analysis and myeloperoxidase (MPO) activity indicated that inflammatory cells infiltrated into the muscle layer at 2 days after 2,4,6‐trinitrobenzenesulphonic acid (TNBS) treatment. The infiltrated immune cells then gradually decreased in number, but were still present at 14 days. The expression of proinflammatory cytokine mRNAs (TNF‐α, IL‐1β and IL‐6) and proteins in the muscle layer was increased at 2 days, then began to decrease, returning to control levels at 14 days. The frequency of spontaneous rhythmicity was suppressed at 2 and 7 days, and returned to control levels at 14 days. Consistent with these observations, the immunoreactivity of the interstitial cells of Cajal network was disrupted at 2 and 7 days, which then gradually reformed at 14 days. On the other hand, the myogenic contractions induced by high K+ and carbachol were decreased at 2 days, and were still inhibited at 14 days. These results suggest that spontaneous rhythmicity dysfunction may improve more rapidly than myogenic contractility dysfunction in a hapten‐induced rat model of colitis.
Searching for HLA‐DRB1*1206 in volunteer marrow donors in four US population groups
Authors: Lazaro A. M. , Steiner N. K. , Cao K. , Slack R. , Chen D. S. , Xiao Y. , Beduhn E. , Ng J. , Hartzman R. J. , Hurley C. K.
Published: September 2006

The frequencies of DRB1*12 alleles were determined in four US population groups by DNA sequencing. Only DRB1*120101 (or DRB1*1206 or *1210) and DRB1*120201 alleles were identified, the latter primarily in the Asian American population. Additional testing of a subset of samples to detect the presence of DRB1*1206 found all of the alleles to be DRB1*120101 (or DRB1*1210). Retesting of six samples previously typed as DRB1*1206 found only DRB1*120101 (or DRB1*1210).
Application of Paramagnetic Beads for Purifying Bacillus anthracis Protective Antigen
Authors: Zarzecka A. , Bartoszcze M.
Published: September 2006

Paramagnetic beads coated with Protein G and Tosylactivated‐280 dynabeads have been used to purify Bacillus anthracis protective antigen from a liquid culture. The obtained protein was used in the enzyme‐linked immunosorbent assay test to detect B. anthracis protective antigen antibodies in human sera collected from immunized individuals. The purification method using paramagnetic beads is very effective. It is fast, easy and may be carried out practically in any laboratory.
Influence of Climatic and Management Factors on Eimeria Infections in Goats from Semi‐arid Zones
Authors: Ruiz A. , González J. F. , Rodríguez E. , Martín S. , Hernández Y. I. , Almeida R. , Molina J. M.
Published: September 2006

A survey of Eimeria infections was performed in dairy goats and kids (<6 months old) of six farms from a dry desert area of Gran Canaria Island (Spain). The number of oocysts per gram of faeces (OPG) was determined by a modified McMaster technique over a total of 2616 individual faecal samples taken from the rectum in monthly intervals. Eimeria oocysts were found in 96.1% of the samples with OPG ranging from 1 × 102 to 1.4 × 106. Kid goats had significantly (P < 0.001) higher OPG counts (46 496 ± 5228) than dairy females (2225 ± 287). Eight Eimeria species were identified, with Eimeria ninakohlyakimovae (30.0%), Eimeria arloingi (28.6%) and Eimeria alijevi (20.5%) being the most frequent species followed by Eimeria caprina (9.1%), Eimeria christenseni (4.5%), Eimeria jolchijevi (3.4%), Eimeria caprovina (3.2%) and Eimeria hirci (0.7%). Although significant differences were observed among goat groups and herds, the eight species were present in the six farms in both dairy goats and kids. The intensity of oocysts shedding was related to some factors such as the size of the herd and was further influenced by the prevailing climatic conditions of the area. The highest OPG counts were recorded during the hot season in dairy goats and close to weaning time in kids reared in small farms having no prophylactic treatments against eimeriosis.
Persistence of Rabbit Haemorrhagic Disease Virus Genome in Vaccinated Rabbits after Experimental Infection
Authors: Gall A. , Schirrmeier H.
Published: September 2006

Rabbit haemorrhagic disease (RHD) is usually a fatal disease in rabbits which has spread rapidly across the continents. While previous studies suggested persistence in rabbits to be an important factor in the epidemiology, the relevance of field virus infection of immune rabbits has not been investigated in experimentally infected animals before. This report describes for the first time the persistence of rabbit haemorrhagic disease virus (RHDV) genome for at least 15 weeks in rabbits immunized with an inactivated vaccine as well as a subunit vaccine and subsequently challenged with virulent RHDV. The viral RNA loads were determined by real‐time reverse transcription‐polymerase chain reaction. No conspicuous association of the detectable amount of RHDV RNA with the type of vaccine, the time after infection and – with one exception – the level of RHDV‐specific antibodies in the immunized animals was observed. The results presented in this study are an urgent evidence for the existence of carrier animals as an important factor in the epidemiology of RHD.
Detection and identification of food‐borne pathogens of the genera Campylobacter, Arcobacter and Helicobacter by multiplex PCR in poultry and poultry products
Authors: Neubauer C. , Hess M.
Published: September 2006

The objective of this study was to develop a multiplex polymerase chain reaction (PCR) to detect and differentiate food‐borne pathogens of the three genera Campylobacter, Arcobacter and Helicobacter in a single step procedure. One common reverse primer and three genus‐specific forward primers were designed by hybridizing to the 16S rRNA of selected reference strains. Besides the species with significance as food‐borne pathogens isolated from poultry meat –Campylobacter jejuni, Campylobacter coli, Arcobacter butzleri and Helicobacter pullorum– several other members of these genera were tested to determine the specificity of the designed multiplex PCR. In total, 20 ATCC and NCTC reference strains of Campyobacter, Arcobacter and Helicobacter were used to evaluate the PCR. Specific amplificates were obtained from all thermophilic species of Campylobacter as well as from species of Arcobacter and Helicobacter. No amplification product was obtained from the non‐thermophilic Campylobacter, C. hyointestinalis and C. fetus. Furthermore, a total of 43 field strains of the three genera isolated from poultry, pigs, cattle and humans were investigated using this PCR. To confirm the classification of 10 H. pullorum strains the 16S rRNAs were sequenced. The developed PCR is a helpful diagnostic tool to detect and differentiate Campylobacter, Arcobacter and Helicobacter isolated from poultry and poultry products.
Incidence of BVDV1 and BVDV2 Infections in Cattle Submitted for Necropsy in Northern Germany
Authors: Liebler‐Tenorio E. M. , Kenklies S. , Greiser‐Wilke I. , Makoschey B. , Pohlenz J. F.
Published: September 2006

The incidence of bovine viral diarrhoea virus (BVDV) 1 and 2 infections was determined in calves, young cattle and older cattle with signs of mucosal disease (MD) submitted for necropsy to three laboratories in Northern Germany between June 2000 and May 2001. At necropsy, tonsils, retropharyngeal lymph nodes, mesenteric lymph nodes, ileal Peyer's patch and spleen were collected and examined by immunohistochemistry and virus isolation. From 311 animals examined, 30 (9.6%) were positive for BVDV. All viral isolates were typed by polymerase chain reaction after reverse transcription using species‐specific primers and determined to be BVDV1. Based on the distribution of lesions and viral antigen, animals with MD, persistent infection (PI) and acute, transient infection could be distinguished. Twelve of the positive animals had characteristic signs of MD: severe diarrhoea, erosive to ulcerative lesions throughout the digestive tract and severe depletion of all lymphoid tissues. Viral antigen was present in all tissues and cell types, but particularly in depleted lymphoid follicles and altered epithelium. In seven calves, viral antigen was detectable in all tissues and cell types, but lesions were mild or missing. This is typical for PI. The remaining 11 calves most likely represent animals with acute, transient infection. Distribution of antigen was more variable, predominantly restricted to lymphoid follicles and often not seen in all tissues examined. Clinical findings were combined bronchopneumonia and enteritis. The detection of BVDV1 in young calves with pneumonia and enteritis emphasizes the importance of BVDV1 and not only BVDV2 for severe respiratory and enteric diseases of calves.
Detection of Echinococcus multilocularis in Foxes: Evaluation of a Protocol of the Intestinal Scraping Technique
Authors: Tackmann K. , Mattis R. , Conraths F. J.
Published: September 2006

The intestinal scraping technique (IST) is widely used for the detection of definitive hosts infected with Echinococcus multilocularis. The sensitivity of the method has been questioned in recent years. Several variations of the technique are used that may differ in their performance. We therefore estimated the diagnostic sensitivity and specificity of the IST protocol used in our lab by examining the small intestines of 210 E. multilocularis‐infected foxes and 294 foxes that had tested negative for this parasite. To this end, IST was first performed on 48 and 294 intestines from infected and uninfected foxes respectively, followed by an examination of the entire remaining mucosa of the small intestine to discover any infections with E. multilocularis that had not been detected by IST. The point estimate for diagnostic sensitivity was 100%. Five different classes of infection intensities were formed. The lower limits of the 95% confidence intervals ranged between 76.8% and 92.6% depending on the number of samples analysed per class. When the small intestines of another 162 infected foxes were examined by IST and the results recorded separately for the anterior, middle and posterior third of the small intestine, a strong preference of E. multilocularis for the posterior third was observed. For epidemiological purposes, it may thus be possible to restrict routine investigations to the posterior portion of the small intestine. By contrast, a reduction of the number of slides examined per infected animal may lead to a considerable loss in sensitivity in animals with a low intensity of infection.
Epithelial microchimerism: Consistent finding in human liver transplants
Authors: Gaia Silvia , Cappia Susanna , Smedile Antonina , Bacillo Elisa , Gaia Ezio , Gubetta Luciano , Rizzetto Mario
Published: September 2006

Background:  Eleven liver biopsies from six male patients who received a liver transplant (LT) from female donors were examined in order to determine whether male host‐derived hepatic cells were present in female grafts that exhibited minimal or important inflammatory damage.

Methods:  Immunohistochemistry for epithelial cell type differentiation (anticytokeratin monoclonal antibody) and fluorescence in situ hybridization for XY chromosomes identification were performed on each slide.

Results:  Host‐derived hepatic cells were found in all except one transplant, with a frequency ranging from 2.3 to 25‰ of the total hepatocytes in the biopsy specimen. They were usually found as isolated cells scattered throughout the hepatic lobule; in one patient they were grouped into little clusters. Host‐derived hepatic cells persisted throughout the histological follow up (up to 535 days after LT). Polyploidy for XY chromosome was observed.

Conclusion:  Hepatocytes derived from extra‐hepatic stem cells are frequently found in small numbers in human liver grafts and persist over time.
Endoscopic reflux esophagitis in patients with upper abdominal pain‐predominant dyspepsia
Authors: Song Ho June , Choi Kee Don , Jung Hwoon‐Yong , Lee Gin Hyug , Jo Ji Yun , Byeon Jeong‐Sik , Yang Suk‐Kyun , Hong Weon‐Seon , Kim Jin‐Ho
Published: September 2006

Background:  Reflux symptom assessment had reliable accuracy in the diagnosis of gastroesophageal reflux disease (GERD). However, patients may recognize heartburn or regurgitation as dyspepsia because of inaccurate understanding or atypical presentation. The aim of the present study was to estimate endoscopic reflux esophagitis in patients with upper abdominal pain as a predominant symptom in the absence of heartburn or regurgitation.

Methods:  Two hundred and sixty‐three consecutive patients presenting dyspepsia without heartburn or regurgitation were enrolled. Patients with heartburn or regurgitation were excluded using the symptom interviewer method. Dyspepsia was categorized into pain‐predominant or dysmotility‐predominant groups according to the Rome II proposal. Endoscopic reflux esophagitis was graded using the Los Angeles classification.

Results:  One hundred and five patients were included in the pain‐predominant group and 119 in the dysmotility‐predominant group. Reflux esophagitis was found in 18.8% (42/224) of all dyspeptic patients. Grade A esophagitis was noted in 27.6% (29/105) of the pain‐predominant group and in 7.6% (9/119) of the dysmotility‐predominant group. Grade B was noted in two patients in each group. A total of 29.5% (31/105) and 9.3% (11/119) had reflux esophagitis, respectively (P < 0.001). Comparing patients with or without reflux esophagitis, there was no difference in body mass index, smoking habit, alcohol consumption, or Helicobacter pylori infection status.

Conclusions:  A significant proportion of patients presenting dyspepsia, especially pain‐predominant dyspepsia, have endoscopic reflux esophagitis. In view of GERD, pain‐predominant dyspepsia should be investigated and managed differently from dysmotility‐predominant dyspepsia.
POINT OF CARE TESTING OF ASPIRIN RESISTANCE IN PATIENTS WITH VASCULAR DISEASE
Authors: Wong Shen , Ward Christopher M. , Appleberg Michael , Lewis David R.
Published: September 2006

Introduction:  The reported range in rates of aspirin resistance (5.5–60%) may reflect difficulties in studying platelet function and the variety of tests used. This study used a platelet function analyzer (PFA‐100) to prospectively document aspirin resistance in a cohort of patients with arterial disease.

Methods:  Patients with internal carotid artery (ICA) stenosis or intermittent claudication (IC) were recruited. Exclusion criteria were contraindications to aspirin, prescription of other medication with known antiplatelet effects or known platelet abnormalities. After prescription of 100 mg aspirin/day for 2 weeks an uncuffed venous blood sample was taken and analysed with the PFA‐100. Aspirin resistance was defined as closure time (CT) less than the upper limit of normal (158 s collagen/epinephrine agonist; 118 s collagen/adenosine diphosphate (ADP) agonist).

Results:  Thirty‐three patients with IC and 12 patients with ICA stenosis were recruited (n = 45). Median (range) age was 74 years (49–85) and the male to female ratio was 1.5:1. The median (range) CT was >300 (85 to >300) s with collagen/epinephrine and 100 (52 to >300) s with collagen/ADP agonist. Twelve patients (27%) in the collagen/epinephrine group had normal CT despite treatment with 100 mg aspirin, indicating resistance. Of the 33 patients with collagen/epinephrine CT prolonged by aspirin, 10 patients also had prolonged collagen/ADP CT, suggesting excessive platelet inhibition.

Conclusion:  A significant proportion of patients taking aspirin do not show laboratory evidence of platelet inhibition and may not be protected from atherothrombotic events. The PFA‐100 appears to be a useful tool to screen for both aspirin resistance and excessive aspirin mediated platelet inhibition.
ARE BIOCHEMICAL VALUES PREDICTIVE OF ADENOMA’S WEIGHT IN PRIMARY HYPERPARATHYROIDISM?
Authors: Hamidi Sepehr , Aslani Afshin , Nakhjavani Manouchehr , Pajouhi Mohammad , Hedayat Anushiravan , Kamalian Nasser
Published: September 2006

Background:  Preoperative laboratory findings may carry some predictive value about the size of the abnormal parathyroid tissue that needs to be removed in primary hyperparathyroidism.

Methods:  In a retrospective study from 1988 to 2003, records of 71 patients with parathyroid adenoma were reviewed. The correlation between preoperative serum calcium, phosphate and parathyroid hormone (PTH) with adenoma’s weight was analysed separately.

Results:  There was a significant correlation between preoperative serum PTH and calcium with adenoma’s weight (P < 0.001 and P = 0.03, respectively). The correlation between preoperative serum phosphate and adenoma’s weight was not significant (P = 0.1).

Conclusion:  Preoperative PTH level cannot be used as a definite guide to the parathyroid adenoma’s weight. Large parathyroid adenomas seem to secrete less PTH per unit weight than small adenomas. Calcium and phosphate do not seem to be of much value in predicting adenoma’s weight in primary hyperparathyroidism.
NEUROLOGICAL DEFICIT AS A PRESENTATION OF OCCULT METASTATIC THYROID CARCINOMA
Authors: Izzard Mark , McIvor Nicholas , Chaplin John , Ianovski Ilia
Published: September 2006

Three cases of occult metastatic thyroid carcinoma presenting with neurological deficits are reviewed. In each case the patient’s initial presentation was with symptoms of neurological deficiency secondary to a spinal cord compression. All patients received a combination of surgery, external beam radiotherapy and postoperative thyroxine treatment. Two of the three patients are alive and well, able to mobilize with minor neurological dysfunction. The diagnosis and management of the patients, as well as their outcomes are reviewed, with a discussion on further management issues alongside a review of the current published work.
PREDICTING FUNCTIONAL CAPACITY OUTCOME 12 MONTHS AFTER HOSPITALIZED INJURY
Authors: Schluter Philip J. , McClure Roderick J.
Published: September 2006

Background:  There is a recognized need to move from mortality to morbidity outcome predictions following traumatic injury. However, there are few morbidity outcome prediction scoring methods and these fail to incorporate important comorbidities or cofactors. This study aims to develop and evaluate a method that includes such variables.

Methods:  This was a consecutive case series registered in the Queensland Trauma Registry that consented to a prospective 12‐month telephone conducted follow‐up study. A multivariable statistical model was developed relating Trauma Registry data to trichotomized 12‐month post‐injury outcome (categories: no limitations, minor limitations and major limitations). Cross‐validation techniques using successive single hold‐out samples were then conducted to evaluate the model’s predictive capabilities.

Results:  In total, 619 participated, with 337 (54%) experiencing no limitations, 101 (16%) experiencing minor limitations and 181 (29%) experiencing major limitations 12 months after injury. The final parsimonious multivariable statistical model included whether the injury was in the lower extremity body region, injury severity, age, length of hospital stay, pulse at admission and whether the participant was admitted to an intensive care unit. This model explained 21% of the variability in post‐injury outcome. Predictively, 64% of those with no limitations, 18% of those with minor limitations and 37% of those with major limitations were correctly identified.

Conclusion:  Although carefully developed, this statistical model lacks the predictive power necessary for its use as a basis of a useful prognostic tool. Further research is required to identify variables other than those routinely used in the Trauma Registry to develop a model with the necessary predictive utility.
EARLY TRAUMA MANAGEMENT SKILLS IN AUSTRALIAN GENERAL PRACTITIONERS
Authors: Lopez Derrick G. , Hamdorf Jeffrey M. , Ward Alison M. , Emery Jon
Published: September 2006

Background:  General practitioners (GPs) have a role in the early management of major trauma in rural Australia. The Early Management of Severe Trauma (EMST) course fulfils their educational needs by providing skills for the systematic management of the seriously injured patient. However, with any skill there is a natural loss over time. This study surveyed GPs who have completed the EMST course to determine their confidence in trauma management.

Methods:  A two‐page survey was mailed in December 2004 to all GPs who had completed an EMST course from 1989 to 2004 and were currently residing in Western Australia. The survey consisted of background questions, open‐ended questions regarding the EMST course and skills confidence ratings using visual analogue scales. The final sample size was 223.

Results:  Response rate was 55%. GPs were least confident in carrying out diagnostic peritoneal lavage and cricothyroidotomy. They were most confident inserting i.v. cannulas and managing fluid replacement. Their confidence in some of these skills were related to the frequency of managing trauma patients but not to the interval since completing the EMST course. GPs found the systematic approach to trauma management and practical/procedural skills as the most relevant components of EMST. They felt that EMST could be improved with more accessible refresher courses and more practical/procedural skills.

Conclusion:  Most of these GPs were involved in rural hospital work where they may be required to manage seriously injured patients. They require regular refresher courses to maintain their confidence levels in treating seriously injured patients.
MANAGEMENT OF POPLITEAL ARTERY ANEURYSMS
Authors: Hamish Maher , Lockwood Alistair , Cosgrove Christine , Walker Alasdair J. , Wilkins Denis , Ashley Simon
Published: September 2006

Background: Popliteal artery aneurysms (PAA) are the most common peripheral aneurysm and are recognized as ‘the silent killer of the leg circulation’. The timing and type of interventions used in their treatment is still controversial. This review examines the published data on the natural history, epidemiology, clinical presentation and management options available. The aim of this study is to try and reach a consensus with regards to the best management of PAA.

Method: A systematic review of data in the English published works since 1980.

Results: The authors include 53 studies containing 2854 patients with 4291 PAA. Most published data involves retrospective studies and personal experience, with one multicentre study. No randomized controlled studies exist regarding the management of PAA.

Conclusions: 1. Although most PAA are of atherosclerotic origin in old patients, trauma, infection and family history are the main causes in young patients.

2. Great vigilance is needed for diagnosis as only approximately five patients are seen each year by a major vascular centre. There is no place for screening programmes to detect PAA.

3. Approximately 45% of patients are asymptomatic at the time of initial diagnosis. Aortic aneurysms are found in 40% and bilateral PAA in 50% of patients. More than 95% of patients are men with a mean age of 65 years and 45% have hypertension.

4. Surgical reconstruction is recommended for all symptomatic and asymptomatic aneurysms larger than 2 cm. Five‐year graft patency rates after surgical repair range from 30 to 97%, with 5‐year limb salvage ranging from 70 to 98%. Patient survival rates at 5 and 10 years are 75 and 46%, respectively.

5. If carried out carefully, intra‐arterial thrombolysis can safely prepare patients presenting with acute ischaemia from occluded PAA, for surgical revascularization to restore distal run‐off.

6. Endovascular repair of a PAA is a feasible option, although little evidence is yet available.

7. Lifelong, careful patient surveillance is essential to detect and treat new aneurysms at other sites.
THE CONUNDRUM OF CLAUDICATION
Authors: Varcoe Ramon L. , Taylor Claire F. , Annett Paul , Jacobsen Erica E. , McMullin Gabrielle
Published: September 2006

Stable claudication has traditionally been treated conservatively by many clinicians as operative therapies involve considerable risk for a condition that is often slowly progressive and non‐fatal. The relative safety of less invasive endovascular techniques brings potential survival benefits from the increased exercise tolerance that result. We aimed to revisit and clarify the aetiologies of intermittent claudication in a review of the rarer causes that can mimic atherosclerotic occlusive disease. An extensive search of Medline, Embase and the Cochrane databases was carried out to compile published work addressing the aetiology of claudication and specific non‐atherosclerotic causes. The reference lists of these manuscripts were also searched for relevant articles. There are several vasculogenic and neurogenic causes for intermittent claudication, many of which are unrelated to atherosclerosis. Recognition of these rarer syndromes is essential when planning endovascular or operative management strategies. Consideration of non‐atherosclerotic differential diagnoses is recommended when assessing the patient with intermittent claudication. This is particularly critical in the young patient whose pattern of symptoms and risk factors may not fit precisely with atherosclerosis.
ANATOMICAL STUDY OF THE ANKLE WITH VIEW TO THE ANTERIOR ARTHROSCOPIC PORTALS
Authors: Solomon Lucian B. , Ferris Linda , Henneberg Maciej
Published: September 2006

This article evaluates the risk of interference with the neurovascular structures in the four anterior ankle arthroscopic portals, described on each side of the extensor tendons: anteromedial, medial midline, anterocentral and anterolateral. Complications after ankle arthroscopies have been described in up to 17%, most being neurovascular. To quantify the neurovascular risks we dissected 68 cadaveric feet and evaluated the correlations between tendons, vessels and nerves. The mean distance between tibialis anterior and extensor hallucis longus and between extensor hallucis longus and extensor digitorum longus is 4 mm, but in 10–20% these tendons are in apposition or are overlapped. The tibialis anterior vascular bundle was absent in 11.8%, was located between the tibialis anterior and the extensor hallucis longus in 3% and between the extensor hallucis longus and the extensor digitorum longus in 64.7%. A peroneal vascular bundle or branches of the tibialis anterior vascular bundle were located lateral to the extensor digitorum longus/peroneus tertius tendon in 88.2%. Transverse vascular branches were identified in 41.2% over the medial side of the joint line and in 52.9% over the lateral side. The deep peroneal nerve was located between the extensor hallucis longus and the extensor digitorum longus tendons in 58.8%. The superficial peroneal nerve had branches located between the tibialis anterior and the extensor hallucis longus tendons in 2.9%, between the extensor hallucis longus and the extensor digitorum longus tendons in 23.5% and lateral to the extensor digitorum longus/peroneus tertius tendon in 32.4%. These results show that the anteromedial and medial midline portals are the safest. The anterolateral portal should be noted not only for the risks to the superficial peroneal nerve, but also to the peroneal vessels.
Ownership, investment climate and firm performance
Authors: Hallward‐Driemeier Mary , Wallsten Scott , Xu Lixin Colin
Published: September 2006

The importance of a country's ‘investment climate’ for economic growth has recently received much attention. In this paper we use a new survey of 1,500 Chinese enterprises in five cities to measure more precisely components of the investment climate and their effects on firm performance. Our firm‐level analysis reveals that both ownership and investment climate measures matter for investment, productivity and growth. In particular, firm performance is positively correlated with foreign and domestic private ownership, light regulatory burdens, limited corruption, technological infrastructure and labour market flexibility. In contrast, gains from improving banking access and physical infrastructure are quite limited.
Barter, credit and welfare
Authors: Noguera José , Linz Susan J.
Published: September 2006

This paper develops a model to investigate the welfare implications of barter in Russia and other transition economies during the 1990s. We argue that barter is a welfare‐improving phenomenon that acts as a defence mechanism against monetary instability. When firms react to tighter credit markets by switching to barter, the risk they face diminishes, allowing for a higher level of production.
The effects of transition and political instability on foreign direct investment inflows
Authors: Brada Josef C. , Kutan Ali M. , Yigit Taner M.
Published: September 2006

This paper examines the effects of transition and of political instability on foreign direct investment (FDI) flows to the transition economies of Central Europe, the Baltics and the Balkans. We find that FDI flows to transition economies unaffected by conflict and political instability exceed those that would be expected for comparable West European countries. Success with stabilization and reform increased the volume of FDI inflows. In the case of Balkan counties, conflict and instability reduced FDI inflows below what one would expect for comparable West European countries, and reform and stabilization failures further reduced FDI to the region. Thus, we find that the economic costs of instability in the Balkans in terms of foregone FDI have been quite high.
Serotonin-Induced Plasma Extravasation in the Murine Inner Ear: Possible Mechanism of Migraine-Associated Inner ear Dysfunction
Authors: Koo J-W , Balaban CD
Published: September 2006

Sensitivity to sound and vertigo are often components of migraine. Recent studies suggest that plasma extravasation from intradural blood vessels may contribute to migraine pain. This study documented plasma extravasation in the mouse inner ear after intravenous administration of serotonin (5-HT). Horseradish peroxidase (HRP) was injected intravenously to trace protein extravasation in mice, followed 15 min later by intravenous 5-HT or saline. Forty-five minutes later, mice were euthanized. HRP extravasation was visualized immunohistochemically and quantified densitometrically. Baseline and evoked extravasation in stria vascularis and tectorial membrane were indistinguishable from skin, dura mater and tympanic membrane. Brain parenchyma, Scarpa's ganglion, basal spiral ganglion and modiolus, and the central vestibular nerve segment showed no significant 5-HT-induced extravasation. In contrast, 5-HT produced extravasation in the apical spiral ganglion, modiolus, and intralabyrinthine superior and inferior vestibular nerve. Thus, inner ear plasma extravasation is a potential mechanism for migraine-associated vertigo and sound sensitivity.