bluuebunny/crossref_metadata_2025 huggingface dataset:
Innate mechanisms for Bifidobacterium lactis to activate transient pro‐inflammatory host responses in intestinal epithelial cells after the colonization of germ‐free rats
Authors: Ruiz Pedro A. , Hoffmann Micha , Szcesny Silke , Blaut Michael , Haller Dirk
Published: July 2005

Bifidobacteria comprise a dominant microbial population group in the human intestinal tract with purported beneficial health effects on the host. In this study, we characterized the molecular mechanisms for the initial interaction of probiotic Bifidobacterium lactis strain BB12 with native and intestinal epithelial cell (IEC) lines. We showed that B. lactis‐monoassociated Fisher F344 rats transiently induce phosphorylation/activation of the NF‐κB transcriptionally active subunit RelA and the mitogen‐activated protein kinase (MAPK) p38 in native IEC at day 5 after initial bacterial colonization. In addition, Interleukin 6 (IL‐6) gene expression was significantly increased at day 5, demonstrating the physiological relevance of transient transcription factor activation in IEC. In contrast, Bacteroides vulgatus‐monoassociated Fisher rats revealed RelA but not p38 MAPK phosphorylation and failed to trigger significant IL‐6 gene expression in native IEC. Moreover, we demonstrated that B. lactis triggers NF‐κB RelA and p38 MAPK phosphorylation in IEC lines. Adenoviral delivery of mutant IKK‐β (Ad5dnIKKβ) and inhibition of the p38 MAPK pathway through the pharmacological inhibitor SB203580 significantly blocked B. lactis‐induced IL‐6 gene expression in IEC, suggesting that B. lactis triggers NF‐κB and MAPK signaling to induce gene expression in the intestinal epithelium. Regarding the mechanisms of bacteria epithelial cell cross‐talk, B. lactis‐induced IL‐6 gene expression was completely inhibited in TLR2 deficient mouse embryogenic fibroblasts (MEF TLR2−/−) as well as TLR2ΔTIR transfected Mode‐K cells. In conclusion, we demonstrated that probiotic bacteria transiently trigger innate signal transduction and pro‐inflammatory gene expression in the intestinal epithelium at early stages of bacterial colonization.
Activation of murine dendritic cells and macrophages induced by Salmonella enterica serovar Typhimurium
Authors: Kalupahana Ruwani Sagarika , Mastroeni Pietro , Maskell Duncan , Blacklaws Barbara Ann
Published: July 2005

Macrophages and dendritic cells (DCs) are antigen‐presenting cells (APCs), and the direct involvement of both cell types in the immune response to Salmonella has been identified. In this study we analysed the phenotypic and functional changes that take place in murine macrophages and DCs in response to live and heat‐killed Salmonella enterica serovar Typhimurium. Both types of cell secreted proinflammatory cytokines and nitric oxide (NO) in response to live and heat‐killed salmonellae. Bacterial stimulation also resulted in up‐regulation of costimulatory molecules on macrophages and DCs. The expression of major histocompatibility complex (MHC) class II molecules by macrophages and DCs was differentially regulated by interferon (IFN)‐γ and salmonellae. Live and heat‐killed salmonellae as well as lipopolysaccharide (LPS) inhibited the up‐regulation of MHC class II expression induced by IFN‐γ on macrophages but not on DCs. Macrophages as well as DCs presented Salmonella‐derived antigen to CD4 T cells, although DCs were much more efficient than macrophages at stimulating CD4 T‐cell cytokine release. Macrophages are effective in the uptake and killing of bacteria whilst DCs specialize in antigen presentation. This study showed that the viability of salmonellae was not essential for activation of APCs but, unlike live bacteria, prolonged contact with heat‐killed bacteria was necessary to obtain maximal expression of the activation markers studied.
Partial molecular characterization, polymorphism and chromosomal localization of the porcine PSMD4 gene
Authors: Wang Y.F. , Li Y. , Liu B. , Yu M. , Fan B. , Zhu M.J. , Xiong T.A. , Li K.
Published: July 2005

The complete coding sequence of porcine PSMD4 gene encoding proteasome 26S non‐ATPase subunit 4 was obtained by the reverse transcriptase‐polymerase chain reaction (RT‐PCR) and deposited in GenBank nucleotide database (AY704418). The nucleotide sequence and the predicted protein sequence shared the high sequence identity with their mammalian counterparts. A G/A single nucleotide polymorphism in intron 9 detected as Hin6I PCR‐restriction fragment length polymorphism (PCR‐RFLP) shows allele frequency differences between Meishan, Erhualian, Tibetan, Large White and Duroc breeds. Analyses of somatic cell hybrid panel (SCHP) and radiation hybrid (IMpRH) panel revealed that PSMD4 gene maps to SSC 4q21‐q23 and closely linked the SW512 (14 cR, LOD = 19.47).
Estimation of genetic parameters for the prevalence of osseous fragments in limb joints of Hanoverian Warmblood horses
Authors: Stock K.F. , Hamann H. , Distl O.
Published: July 2005

Genetic parameters were estimated for the prevalence of osseous fragments in distal (DIJ) and proximal interphalangeal (PIJ), fetlock (FJ) and hock joints (HJ) of Hanoverian Warmblood horses by using residual maximum likelihood (REML) with linear animal models. The analyses were based on the results of 10 standardized radiographs of all four limbs of 3725 young riding horses selected for sale at auction. Transformation factors onto the underlying liability scale were verified by a simulation study. The heritability estimates of osseous fragments on the liability scale were in the range ofh2 = 0.19–0.60. Further analyses of osseous fragments in FJ and HJ were performed separately in males and females. In both sexes, the heritabilities of osseous fragments in HJ were higher (h2 = 0.41 in males,h2 = 0.25 in females) than those of osseous fragments in FJ (h2 = 0.21 in males,h2 = 0.23 in females). Osseous fragments in the phalangeal joints (DIJ, PIJ, FJ) were genetically correlated moderately positive (rg = 0.19–0.41). The genetic correlations between osseous fragments in the phalangeal joints and in HJ were negative (rg = −0.27 to −0.67). Particularly, this applied to osseous fragments in FJ in both sexes, to those in front FJ in males and to osseous fragments in front and hind FJ of females (up torg = −1). The heritability of height at withers was estimated ath2 = 0.27–0.28. Genetic correlations between height at withers and osseous fragments in equine limb joints were mostly moderately positive (up torg = 0.75). We conclude from our results that osseous fragments in phalangeal and hock joints are genetically different traits but sex‐specific expression of osseous fragments was unlikely.
Renal cell carcinoma with cutaneous metastases
Authors: Lim Cathy , Chan Renee , Regan William
Published: July 2005

An 86‐year‐old man presented with multiple papules on his face, neck, lips and ears 4 years after a left nephrectomy for renal cell carcinoma. Shave biopsies and excisions of the cutaneous lesions revealed findings consistent with metastatic renal cell carcinoma of clear cell type. The patient continued to present to the clinic over the next 3 years with similar eruptions, and biopsies continued to confirm renal cell carcinoma. During this time, metastases to the bone, lung, soft palate and posterior leg were also diagnosed. This case represents an unusual clinical presentation of metastatic renal cell carcinoma. It shows that a high index of suspicion should be maintained as cutaneous metastases can mimic other skin conditions.
Pyoderma gangrenosum complicated by herpes simplex virus infection
Authors: Tai Yee J , Kelly Robert
Published: July 2005

High‐dose immunosuppression used in the treatment of pyoderma gangrenosum predisposes patients to opportunistic infections. A 66‐year‐old man presented with recalcitrant pyoderma gangrenosum in which the ulcer itself became infected with herpes simplex virus type 1. This patient was immunosuppressed with multiple agents including topical and oral corticosteroids, cyclosporin, mycophenolate mofetil, intravenous immunoglobulin and infliximab. However, the patient's ulcer continued to extend despite this. It was not until the presence of this virus was detected using polymerase chain reaction on a viral swab of the lesion and oral aciclovir was commenced that the ulcer began to heal. In addition, a fungal granuloma developed on this patient's left forearm as a complication of the potent immunosuppression, which was resolved following treatment with oral voriconazole.
Foreign body reaction involving a Mantoux test site
Authors: Kim Youngjin , Dawes‐Higgs Elizabeth , Zagarella Samuel
Published: July 2005

A 41‐year‐old woman presented with a history of a solitary pustular erythematous lesion occurring at the site of a Mantoux test performed 10 months previously. The histopathology examination revealed a suppurative and foreign body giant cell reaction to numerous keratin flakes. Culture of the tissue was negative for both aerobic and anaerobic organisms including mycobacteria. We postulate that the reaction in our patient may have been secondary to the implantation of epidermal keratin or the entrapment of hair into the dermis during the intradermal injection of tuberculin purified protein derivative.
Toxic epidermal necrolysis secondary to angioimmunoblastic T‐cell lymphoma
Authors: Jones Brad , Vun Yin , Sabah Muna , Egan Conleth A
Published: July 2005

A 67‐year‐old man presented with a history of lymphadenopathy, fevers and separate skin eruptions of erythrodermic spongiotic dermatitis initially and subsequent toxic epidermal necrolysis. Initial lymph node biopsies showed non‐specific granulomatous changes, and skin biopsies and bone marrow aspirate were not diagnostic. His toxic epidermal necrolysis responded well to 3 days of intravenous immunoglobulin. The patient was discharged from hospital and reviewed regularly as an outpatient. Due to persisting lymphadenopathy, further lymph node biopsy led to the diagnosis of angioimmunoblastic T‐cell lymphoma, a rare form of peripheral T‐cell lymphoma with a poor prognosis. At the time of diagnosis his condition deteriorated rapidly and he died soon after.
Blue rubber bleb naevus syndrome associated with cortical blindness
Authors: Shannon Jack , Auld John
Published: July 2005

An 83‐year‐old woman was admitted for investigation of sudden loss of vision. Extensive plum‐purple papules and nodules involved her skin and lips but not mucosae. A cutaneous biopsy demonstrated irregular vascular cavernous channels in the dermis and subcutis; deeper vessels displayed smooth muscle. Blue rubber bleb naevus syndrome was diagnosed. This patient had no gastrointestinal symptoms, no family history of blue rubber bleb naevus syndrome, and only developed cutaneous signs after 60 years of age. Magnetic resonance imaging of the brain found multiple cerebral and cerebellar cavernomas with two larger foci of haemorrhage in both occipital lobes, with the largest in the right occipital lobe being associated with calcification. These most likely represent bleeding in relation to cavernomas believed to be the cause of decreased vision, predominantly in the left eye.
In vitro decondensation of the sperm chromatin in Holothuria tubulosa (sea cucumber) not affecting proteolysis of basic nuclear proteins
Authors: Del Valle Luis J.
Published: July 2005

Sea urchin and sea star oocyte extracts contain proteolytic activities that are active against sperm basic nuclear proteins (SNBP). This SNBP degradation has been related to the decondensation of sperm chromatin as a possible model to male pronuclei formation. We have studied the presence of this proteolytic activity in Holothuria tubulosa (sea cucumber) and its possible relationship with sperm nuclei decondensation. The mature oocyte extracts from H. tubulosa contain a proteolytic activity to SNBP located in the macromolecular fraction of the egg‐jelly layer. SNBP degradation occurred both on sperm nuclei and on purified SNBP, histones being more easily degraded than protein Øo (sperm‐specific protein). SNBP degradation was found to be dependent on concentration, incubation time, presence of Ca2+, pH, and this activity could be a serine‐proteinase. Thermal denaturalization of the oocyte extracts (80°C, 10–15 min) inactivates its proteolytic activity on SNBP but does not affect sperm nuclei decondensation. These results would suggest that sperm nuclei decondensation occurs by a mechanism different from SNBP degradation. Thus, the sperm nuclei decondensation occurs by a thermostable factor(s) and the removal of linker SNBP (H1 and protein Øo) will be a first condition in the process of sperm chromatin remodeling.
Comparison of serum cardiac troponin T and creatine kinase MB isoenzyme mass concentrations in asphyxiated term infants during the first 48 h of life
Authors: Boo Nem‐Yun , Hafidz Hasri , Nawawi Hapizah M , Cheah Fook‐Choe , Fadzil Yong‐Junina , Abdul‐Aziz Bilkis B , Ismail Zulkifli
Published: July 2005

Objective: This prospective study aimed to compare serum creatine kinase MB isoenzyme (CK‐MB) mass concentrations and cardiac troponin T (cTnT) concentrations during the first 48 h of life in asphyxiated term infants.

Methods: Serum cTnT and CK‐MB mass concentrations of 50 term infants with clinical features of perinatal asphyxia were measured at birth and at 12, 24 and 48 h of age by chemiluminescence immunoassay. These infants were followed up until discharge or death. Cord blood CK‐MB and cTnT concentrations of 50 healthy term infants were also assayed.

Results: At birth, asphyxiated infants had significantly higher concentrations of cTnT and CK‐MB than controls (P < 0.0001). Serum cTnT of asphyxiated infants with low ejection fraction <60% was significantly higher at 12 and 24 h than those with normal ejection fraction (P < 0.05). Asphyxiated infants with congestive cardiac failure had significantly higher serum cTnT concentration during the first 48 h of life than those without congestive cardiac failure (P ≤ 0.04). Serum cTnT concentrations during the first 48 h of life were significantly higher in asphyxiated infants who died than those who survived (P < 0.0001). There was no significant difference in serum CK‐MB mass concentrations between asphyxiated infants with and without these complications (P ≥ 0.1).

Conclusion: Unlike CK‐MB, serum cTnT concentrations are significantly higher in asphyxiated infants who die or develop cardiac dysfunction.
Trichophyton rubrum skin infection in two premature infants
Authors: Battin Malcolm R , Wilson Elizabeth M
Published: July 2005

Abstract:  Trichophyton rubrum is a dermatophyte that causes tinea infection in adults and children but infection is surprisingly rare in the preterm infant. We present two cases of T. rubrum infection in preterm infants, in which mother‐to‐child transmission appears to have occurred. We describe the clinical features, differential diagnosis, appropriate investigation and management of this condition.
Drug treatment of neonatal seizures by neonatologists and paediatric neurologists
Authors: Carmo Kathryn Browning , Barr Peter
Published: July 2005

Objective:  To survey anti‐epileptic drug (AED) treatment of early‐onset neonatal seizures by neonatologists and paediatric neurologists.

Methods:  A self‐administered questionnaire was posted to Australian and New Zealand neonatologists and paediatric neurologists. Participants were given the hypothetical case of a full‐term infant with early‐onset seizures following perinatal asphyxia and asked to nominate their preferred AED for treatment of three seizure episodes during the first 24 h.

Results:  One hundred and seven (57%) of 187 individuals answered the questionnaire:  neonatologists responded more often than neurologists (χ2 (1,187) = 7.18, P = 0.007). Phenobarbitone was used by 95% of the respondents to treat the first episode of seizures and 75% of them used an appropriate loading dose (20 mg/kg). Phenobarbitone was used by 84 and 40% of the respondents to treat the second‐ and third‐seizure episodes, respectively. Neonatologists used phenobarbitone, phenytoin and a benzodiazepine with equal frequency to treat a third episode of seizures, whereas neurologists rarely used a benzodiazepine. Neonatologists used significantly larger total doses of phenobarbitone than neurologists. Very few respondents used pyridoxine to treat recurrent seizures that were historically linked to perinatal asphyxia and hypoxic–ischaemic encephalopathy. Neonatologists were more likely than neurologists to discontinue AED within a few days of seizure cessation (χ2 (1,106) = 11.60, P = 0.0006).

Conclusions:  Australian and New Zealand neonatologists and paediatric neurologists generally use phenobarbitone to treat neonatal seizures presumed to be owing to hypoxic–ischaemic encephalopathy, though they do not always use appropriate doses. Neonatologists use phenobarbitone, phenytoin or a benzodiazepine for second and third episodes of seizures, whereas neurologists tend not to use benzodiazepines. Neonatologists use larger total doses of phenobarbitone than neurologists in pursuit of seizure control. Neonatologists discontinue AED earlier than neurologists.
Laparoscopy compared with laparotomy for the surgical staging of endometrial carcinoma
Authors: Wong Chung K. , Wong Yuen H. , Lo Leslie S. F. , Tai Chark M. , Ng Tai K.
Published: July 2005

Aim: To evaluate and compare laparoscopic‐assisted surgical staging with conventional laparotomy for the treatment of endometrial carcinoma.

Methods: From July 2001 to December 2003, a retrospective review of patients with endometrial carcinoma was carried out. The medical records of those patients who had undergone surgical staging with hysterectomy, bilateral salpingo‐oophorectomy and pelvic lymphadenectomy (PLN) were evaluated. Primary outcome measures were operating time (OT), estimated blood loss, total number of lymph nodes yielded, intraoperative complications, postoperative complications, and length of hospital stay.

Result: A total of 64 cases were identified. Two cases were excluded because of incomplete records. Two cases with para‐aortic lymphadenectomy and four cases with Wertheim's hysterectomy were excluded from the study. Thirty‐six patients underwent laparotomy with total abdominal hysterectomy and bilateral salpingo‐oophorectomy and PLN (laparotomy group). Twenty patients underwent the same surgery by laparoscopy, of which 19 were successfully carried out (laparoscopy group). One case was converted to laparotomy. The mean OT in the laparoscopy group was longer when compared with the laparotomy group (211 min vs 94 min, P < 0.001). The mean estimated blood loss in the laparoscopy group was less (200 mL vs 513 mL, P < 0.001). The post‐operative hospital stay was shorter in the laparoscopy group (3.6 days vs 7.7 days, P < 0.001). The mean number of lymph nodes yielded was more in the laparoscopy group (26.1 vs 16.7, P = 0.004). Neither group had intraoperative complications and both had similar postoperative complication rates.

Conclusion: Laparoscopic‐assisted surgical staging for endometrial carcinoma is associated with significantly less blood loss, shorter hospital stay, longer OT time, and more lymph nodes yielded when compared with laparotomy.
Report of 50 cases of eclampsia
Authors: Noraihan Mohd Nordin , Sharda Priya , Jammal Ahmad B. E.
Published: July 2005

Aim: To ascertain the characteristics, clinical features, and maternal fetal outcome in eclampsia in a tertiary referral center with 24 000 deliveries per year.

Methods: This is a cross‐sectional study, in which 50 case notes were retrieved retrospectively and data was analyzed descriptively.

Results: Eclampsia was significant in the Malay primipara patients (n = 14, P = 0.034) and the 20–24‐year‐old primipara patients (n = 11, P = 0.01). Most were significantly antepartum (64%) and preterm seizures (68%), and 16% were early onset (<31 weeks). Two‐thirds were booked and one‐third were inpatients. Twenty per cent did not have hypertension or pre‐eclampsia antenatally. Most presented with headache (66%) and hyper‐reflexia (48%). Only 16% presented with all three prodromal symptoms and 14% were asymptomatic. Half had diastolic blood pressure (DBP) of <110 mmHg and the level of DBP was not significantly associated with the presence of prodromal symptoms and signs. There was increased morbidity, operative intervention, admission to intensive care and more low birth weight babies. Most babies that weighed <2.5 kg had poor Apgar score at 1 min, but most babies had good Apgar score at 5 min (16 babies >2.5 kg, 22 babies ≤2.5 kg, P = 0.006). The corrected perinatal mortality was 40/1000.

Conclusion: There was increased maternal and perinatal morbidity but no maternal mortality. Contributing factors are the atypical presentation, early onset of disease and the absence of risk factors. There is a need to develop new methods to identify this group of patients in an effort to further reduce the prevalence of this dangerous condition.
Aggressive angiomyxoma of the vulva extending into the pelvis: Report of two cases
Authors: Dragoumis Konstantinos , Drevelengas Antonios , Chatzigeorgiou Konstantinos , Assimakopoulos Efstratios , Venizelos Ioannis , Togaridou Eleonora , Mikos Themistoklis , Boulogianni Glykeria , Bontis John
Published: July 2005

Aggressive angiomyxoma is a rare soft‐tissue neoplasm found mainly in the female pelvis. Approximately 130 cases have been reported in the literature to date. In most cases treatment consists of surgical resection, but local recurrence rates remain high (36–72%). Therefore, long‐term follow up is necessary and magnetic resonance imaging seems to be the preferred method for detecting recurrence. We report our experience of a primary and a recurrent aggressive angiomyxoma.
Analysis of retroperitoneal tumors operated on in a gynecology clinic
Authors: Kayikcioglu Fulya , Haberal Ali , Caglar Gamze , Koc Sevgi , Gunes Muzeyyen
Published: July 2005

Aim: To evaluate the patients with retroperitoneal tumors that presented as pelvic mass and were operated on in our gynecology clinic.

Methods: Records of 16 patients were analyzed retrospectively.

Results: All patients had a palpable mass on physical examination and abdominal pain was the most frequent symptom. The median diameter of the tumors was 15 cm. The postoperative histopathology of the patients was leiomyosarcoma in nine, retroperitoneal fibrosis in three, and paraganglioma, hamartoma, and dermoid cyst in three patients. All the tumors were excised almost completely. The incorrect preoperative diagnosis of the patients in this study is due to the presentation of the patients with non‐specific symptoms and not considering the less common differential diagnosis of a pelvic mass.

Conclusion: For clinical signs of vascular or rectal displacement, or where there is evidence of ureteric obstruction, retroperitoneal pathology should be kept in mind.
Multicellular organization in bacteria as a target for drug therapy
Authors: André Jean‐Baptiste , Godelle Bernard
Published: July 2005

Antibiotic treatments are now reaching the limit of their efficiency, especially in hospitals where certain bacteria are resistant to all available drugs. The development of new drugs against which resistance would be slower to evolve is an important challenge. Recent advances have shown that a potential strategy is to target global properties of infections instead of harming each individual bacterium. Consider an analogy with multicellular organisms. In order to kill an animal two strategies are possible. One can kill each of its cells individually. This is what antibiotics do to get rid of bacterial infections. An alternate way, for instance, is to disorganize the hormonal system of animal's body, leading eventually to its death. This second strategy could also be employed against infections, in place of antibiotics. Bacteria are indeed often involved into coordinated activities within a group, and certain drugs are able to disorganize these activities by blocking bacterial communication. In other words, these drugs are able to target infections as a whole, rather than individuals within infections. The present paper aims at analysing the consequence of this peculiarity on the evolution of bacterial resistance. We use a mathematical model, based on branching process, to calculate the fixation probability of a mutant resistant to this type of drug, and finally to predict the speed of resistance evolution. We show that this evolution is several orders of magnitude slower than in the case of antibiotic resistance. The explanation is as follows. By targeting treatments against adaptive properties of groups instead of individuals, we shift one level up the relevant unit of organization generating resistance. Instead of facing billions of bacteria with a very rapid evolutionary rate, these alternate treatments face a reduced number of larger organisms with lower evolutionary potential. In conclusion, this result leads us to emphasize the strong potential of anti‐bacterial treatments aiming at disorganizing social traits of microbes rather than at killing every individual.
Spatial epidemiology and natural population structure of Campylobacter jejuni colonizing a farmland ecosystem
Authors: French Nigel , Barrigas Mishele , Brown Patrick , Ribiero Paulo , Williams Nicola , Leatherbarrow Howard , Birtles Richard , Bolton Eric , Fearnhead Paul , Fox Andrew
Published: July 2005

Recent progress in determining the population structure of Campylobacter jejuni, and discerning associations between genotypes and specific niches, has emphasized the shortfall in our understanding of the ecology and epidemiology of this bacterium. We examined the natural structure of the C. jejuni community associated with cattle farmland in the UK by structured spatiotemporal sampling of habitats, including livestock and wild animal faeces, environmental water and soil, over a 10‐week period within a 100 km2 area. A total of 172 isolates were characterized using multilocus sequence typing into 65 sequence types (STs). Isolates from cattle faeces were significantly over‐represented in the ST‐61 complex, whereas isolates from wildlife faeces and water were more likely to belong to the ST‐45 complex and a number of unusual STs, many of which were first encountered during this study. Sampling within a narrow spatiotemporal window permitted the application of novel statistical methods exploring the relationship between the genetic relatedness and spatial separation of isolates. This approach showed that isolates from the same sampling squares and squares separated by <1.0 km were genetically more similar than isolates separated by greater distances. Our study demonstrates the potential of multilocus sequence typing combined with spatial modelling in exploring natural transmission pathways for C. jejuni.
Growth phase dependent regulation of protein composition in Rhodopirellula baltica
Authors: Gade Dörte , Stührmann Torben , Reinhardt Richard , Rabus Ralf
Published: July 2005

Growth phase dependent changes of protein composition in the marine bacterium Rhodopirellula baltica were quantitatively monitored by applying the two‐dimensional difference gel electrophoresis (2D DIGE) technology. The number of regulated proteins (fold changes in protein abundance > |2|) increased from early (10) to late stationary growth phase (179), with fold changes reaching maximal values of 40. About 110 of these regulated protein spots were analysed by MALDI‐TOF‐MS and identified by mapping of peptide masses. Results indicate an opposing regulation of tricarboxylic acid cycle and oxidative pentose phosphate cycle, a downregulation of several enzymes involved in amino acid biosynthesis and an upregulation of the alternative sigma factor σ H in stationary phase. Interestingly, 26 proteins of unknown function were up‐ or downregulated in the stationary phase. Several proteins were specifically regulated during growth on solid surface (agar plates). These proteins could possibly be involved in the development of the different R. baltica morphotypes, i.e. motile swarmer cells and sessile cell aggregates (so‐called rosettes).
Diversity of bacteria associated with the coral Pocillopora damicornis from the Great Barrier Reef
Authors: Bourne David G. , Munn Colin B.
Published: July 2005

The microbial community associated with the reef building coral Pocillopora damicornis located on the Great Barrier Reef was investigated using culture‐independent molecular microbial techniques. The microbial communities of three separate coral colonies were assessed using clone library construction alongside restriction fragment length polymorphism and phylogenetic analysis. Diversity was also investigated spatially across six replicate samples within each single coral colony using 16S rDNA and rpoB‐DGGE analysis. Clone libraries demonstrated that the majority of retrieved sequences from coral tissue slurry libraries affiliated with γ‐Proteobacteria. This contrasted with clone libraries of seawater and coral mucus, which were dominated by α‐Proteobacteria. A number of retrieved clone sequences were conserved between coral colonies; a result consistent with previous studies suggesting a specific microbe–coral association. rpoB‐DGGE patterns of replicate tissue slurry samples underestimated microbial diversity, but demonstrated that fingerprints were identical within the same coral. These fingerprints were also conserved across coral colonies. The 16S rDNA‐DGGE patterns of replicate tissue slurry samples were more complex, although non‐metric multidimensional scaling (nMDS) analysis showed groupings of these banding patterns indicating that some bacterial diversity was uniform within a coral colony. Sequence data retrieved from DGGE analysis support clone library data in that the majority of affiliations were within the γ‐Proteobacteria. Many sequences retrieved also affiliated closely with sequences derived from previous studies of microbial diversity of healthy corals in the Caribbean. Clones showing high 16S rDNA sequence identity to both Vibrio shiloi and Vibrio coralliilyticus were retrieved, suggesting that these may be opportunist pathogens. Comparisons of retrieved microbial diversity between two different sampling methods, a syringe extracted coral mucus sample and an airbrushed coral tissue slurry sample were also investigated. Non‐metric multidimensional scaling of clone library data highlighted that clone diversity retrieved from a coral mucus library more closely reflected the diversity of surrounding seawater than a corresponding coral tissue clone library.
Grazing impact of different heterotrophic nanoflagellates on eukaryotic (Ostreococcus tauri ) and prokaryotic picoautotrophs (Prochlorococcus and Synechococcus)
Authors: Christaki Urania , Vázquez‐Domínguez Evaristo , Courties Claude , Lebaron Phillipe
Published: July 2005

Autotrophic picoplankton (<3 µm) composed of both prokaryotes and eukaryotes are the most abundant primary producers on Earth. In this study we examined the ingestion of the picoeukaryote Ostreococcus tauri by different marine heterotrophic nanoflagellates (HNF) with various morphologies, swimming and feeding behaviours. Cultures of specific bacterivorous nanoflagellates (Rhynchomonas nasuta, Jakoba libera, and a culture of Cafeteria sp./Monosiga sp.) and natural nanoflagellate populations were used as grazers. For comparison with Ostreococcus, we used similar‐sized prokaryotes as prey, Prochlorococcus and Synechococcus. We observed large species‐specific differences in terms of: use  of picoautotrophs among nanoflagellates, time lag between   prey   addition   and   prey   consumption (0–196 h), grazing rate (0–0.12 h−1), growth rate (0–0.3 h−1) and maximum abundance of HNF reached in experimental bottles (e.g. from 104 to 105 cells ml−1, for a natural coastal population and a Cafeteria sp./Monosiga sp. culture feeding Ostreococcus respectively). Overall, this study shows that the nanoflagellate community composition is conclusive for picoautotrophic community structure and, vice versa, the picoautotrophic community structure favours or inhibits the growth of some nanoflagellate groups.
Ocular parameters related to drug delivery in the canine and equine eye: aqueous and vitreous humor volume and scleral surface area and thickness
Authors: Gilger Brian C. , Reeves Keri‐Ann , Salmon Jacklyn H.
Published: July 2005

Objective  To measure the ocular surface area, scleral thickness, and the aqueous and vitreous humor volumes in the canine and equine eye.

Animals studied  Fourteen canine and 16 equine cadaver eyes.

Procedure  Eyes were measured either fresh or following fixation in formalin. Ocular surface area was calculated using the fluid displacement method. Globes were hemisected and aqueous and vitreous humor were collected and quantitated. Scleral thickness was measured by digital caliper, by image projection, and by ultrasonic biomicroscopy (UBM).

Results  Mean ± standard deviation (SD) scleral surface areas in canine and equine eyes were 12.87 ± 2.24 and 57.23 ± 5.63 cm2, respectively. Mean ± SD aqueous humor volume was 0.77 ± 0.24 in the dog and 3.04 ± 1.27 mL in the horse. Mean vitreous humor volume was 1.7 ± 0.86 mL for the canine eye and 26.15 ± 4.87 mL for the equine eye. In canine and equine eyes, the sclera was thinnest at the ocular equator: 0.34 ± 0.13 mm (canine) and 0.53 ± 0.1 (equine). There were no significant differences between the direct caliper and projected thickness measurements or differences between measurements in the superior, inferior, nasal, and temporal quadrants of the eye. Scleral thickness in fresh tissue was greater than in fixed tissue at most sites.

Conclusions  The UBM measurement method appeared to be most consistent and reproducible when compared to direct measurement techniques. Formalin fixation of the eyes was associated with significantly thinner scleral tissue than with fresh ocular tissue.
How the Spatial Frequency of Polarization Influences the Induction of Reentry in Cardiac Tissue
Authors: BEAUDOIN DEBORAH LANGRILL , ROTH BRADLEY J.
Published: July 2005

Introduction: The mechanism by which an electric field induces a rotor during cross‐field stimulation of cardiac tissue is not entirely known. Different heterogeneous aspects of cardiac tissue have been offered as possible theories, a prominent one being fiber curvature. The polarization produced when an electric field is applied to a sheet of tissue is varied over many spatial frequencies, depending upon the fiber angle. This article compares the effect of high and low spatial frequencies of polarization on reentry induction.

Methods and Results: We incorporate a randomized fiber angle geometry into a two‐dimensional active cardiac tissue model with unequal anisotropy ratios already exhibiting smooth, curving fibers. We simulate cross‐field stimulation to initiate reentry in the tissue model, and compare the electric field thresholds at different S1–S2 intervals for tissue with randomized fiber angles, tissue with a smooth fiber geometry, and tissue with randomized fiber angles plus smooth, curving fibers. The tissue with both small, random fiber angles and curving fibers has a significantly lower threshold for reentry at certain intervals on the strength‐interval curve than for the two cases individually.

Conclusion: Cardiac tissue exhibiting a random fiber geometry in conjunction with a smooth fiber geometry includes high and low spatial frequencies of polarization that may have an effect on the mechanism for reentry at certain S1–S2 intervals. Low spatial frequency regions of hyperpolarization carve out excitable pathways, and high spatial frequency regions provide the large gradient of transmembrane potential required to initiate break excitation.
Assessment of Cardiac Baroreflex Function During Fixed Atrioventricular Pacing Using Baroreceptor‐Stroke Volume Reflex Sensitivity
Authors: YASUMASU TOMIYA , ABE HARUHIKO , OGINOSAWA YASUSHI , TAKAHARA KAZUO , NAKASHIMA YASUHIDE
Published: July 2005

Introduction: The baroreceptor‐heart rate (HR) reflex has prognostic value in cardiovascular medicine. However, it cannot be used in chronotropically incompetent or paced patients. In healthy subjects, the baroreceptor‐stroke volume (SV) reflex, with power spectral analysis of SV and blood pressure (BP) variations in the low‐frequency band, serves as an alternate measure of the baroreceptor‐cardiac reflex. This study examined the baroreceptor‐stroke volume (SV) reflex sensitivity in the supine and 60° upright positions in paced patients.

Methods and Results: We studied 16 recipients of dual‐chamber pacemakers paced at a fixed rate. The hemodynamics and baroreceptor‐SV reflex sensitivity were measured during atrioventricular (AV) sequential pacing every 5 minute in the supine and 60° upright positions. Mean SV decreased from 42.0 ± 20.1 mL in the supine to 36.6 ± 16.1 mL in the upright position (P < 0.05), whereas BP and total peripheral resistance did not change. A significant fall in baroreceptor‐SV reflex sensitivity from 29.2 ± 18.0%/mmHg to 19.5 ± 15.5%/mmHg was observed during upright tilt (P < 0.005).

Conclusion: Fixed‐rate AV sequential pacing did not blunt the decrease in baroreceptor‐SV reflex sensitivity consistent with the arterial baroreflex gain response to upright posture. The decreased baroreceptor‐SV reflex sensitivity occurring with the upright posture may reflect a baroreflex‐induced inotropic effect secondary to vagal withdrawal and sympathetic activation.
Gold‐Tip Electrodes—A New “Deep Lesion” Technology for Catheter Ablation? In Vitro Comparison of a Gold Alloy Versus Platinum–Iridium Tip Electrode Ablation Catheter
Authors: LEWALTER THORSTEN , BITZEN ALEXANDER , WURTZ, Ph.D. SABINE , BLUM, Ph.D. ROBERT , SCHLODDER, Ph.D. KARSTEN , YANG ALEXANDER , LICKFETT LARS , SCHWAB JÖRG O. , SCHRICKEL JAN W. , TIEMANN KLAUS , LINHART MARKUS , ZIMA ENDRE , MERKELY BELA , LÜDERITZ BERNDT
Published: July 2005

Radiofrequency (RF) catheter ablation is widely used to induce focal myocardial necrosis using the effect of resistive heating through high‐frequency current delivery. It is current standard to limit the target tissue–electrode interface temperature to a maximum of 60–70°C to avoid char formation. Gold (Au) exhibits a thermal conductivity of nearly four times greater than platinum (Pt–Ir) (3.17 W/cm Kelvin vs 0.716 W/cm Kelvin), it was therefore hypothesized that RF ablation using a gold electrode would create broader and deeper lesions as a result of a better heat conduction from the tissue–electrode interface and additional cooling of the gold electrode by “heat loss” to the intracardiac blood. Both mechanisms would allow applying more RF power to the tissue before the electrode–tissue interface temperature limit is reached. To test this hypothesis, we performed in vitro isolated liver and pig heart investigations comparing lesion depths of a new Au‐alloy‐tip electrode to standard Pt–Ir electrode material.

Mean lesion depth in liver tissue for Pt–Ir was 4.33 ± 0.45 mm (n = 60) whereas Au electrode was able to achieve significantly deeper lesions (5.86 ± 0.37 mm [n = 60; P < 0.001]). The mean power delivered using Pt–Ir was 6.95 ± 2.41 W whereas Au tip electrode delivered 9.64 ± 3.78 W indicating a statistically significant difference (P < 0.05). In vitro pig heart tissue Au ablation (n = 20) increased significantly the lesion depth (Au: 4.85 ± 1.01 mm, Pt–Ir: 2.96 ± 0.81 mm, n = 20; P < 0.001). Au tip electrode again applied significantly more power (P < 0.001).

Gold‐tip electrode catheters were able to induce deeper lesions using RF ablation in vitro as compared to Pt–Ir tip electrode material. In liver and in pig heart tissue, the increase in lesion depth was associated with a significant increase in the average power applied with the gold electrode at the same level of electrode–tissue temperature as compared to platinum material.
Variance Estimation in Clinical Studies with Interim Sample Size Reestimation
Authors: Miller Frank
Published: July 2005

Summary We consider clinical studies with a sample size reestimation based on the unblinded variance estimation at some interim point of the study. Because the sample size is determined in such a flexible way, the usual variance estimator at the end of the trial is biased. We derive sharp bounds for this bias. These bounds have a quite simple form and can help for the decision if this bias is negligible for the actual study or if a correction should be done. An exact formula for the bias is also provided. We discuss possibilities to get rid of this bias or at least to reduce the bias substantially. For this purpose, we propose a certain additive correction of the bias. We see in an example that the significance level of the test can be controlled when this additive correction is used.
On a Supplemented Case–Control Design
Authors: Pfeiffer Ruth M. , Chatterjee Nilanjan
Published: July 2005

Summary The supplemented case–control design consists of a case–control sample and of an additional sample of disease‐free subjects who arise from a given stratum of one of the measured exposures in the case–control study. The supplemental data might, for example, arise from a population survey conducted independently of the case–control study. This design improves precision of estimates of main effects and especially of joint exposures, particularly when joint exposures are uncommon and the prevalence of one of the exposures is low. We first present a pseudo‐likelihood estimator (PLE) that is easy to compute. We further adapt two‐phase design methods to find maximum likelihood estimates (MLEs) for the log odds ratios for this design and derive asymptotic variance estimators that appropriately account for the differences in sampling schemes of this design from that of the traditional two‐phase design. As an illustration of our design we present a study that was conducted to assess the influence to joint exposure of hepatitis‐B virus (HBV) and hepatitis‐C virus (HCV) infection on the risk of hepatocellular carcinoma in data from Qidong County, Jiangsu Province, China.
Adjusting O'Brien's Test to Control Type I Error for the Generalized Nonparametric Behrens–Fisher Problem
Authors: Huang Peng , Tilley Barbara C. , Woolson Robert F. , Lipsitz Stuart
Published: July 2005

Summary O'Brien (1984, Biometrics40, 1079–1087) introduced a simple nonparametric test procedure for testing whether multiple outcomes in one treatment group have consistently larger values than outcomes in the other treatment group. We first explore the theoretical properties of O'Brien's test. We then extend it to the general nonparametric Behrens–Fisher hypothesis problem when no assumption is made regarding the shape of the distributions. We provide conditions when O'Brien's test controls its error probability asymptotically and when it fails. We also provide adjusted tests when the conditions do not hold. Throughout this article, we do not assume that all outcomes are continuous. Simulations are performed to compare the adjusted tests to O'Brien's test. The difference is also illustrated using data from a Parkinson's disease clinical trial.
Nonparametric Estimation of ROC Curves in the Absence of a Gold Standard
Authors: Zhou Xiao‐Hua , Castelluccio Pete , Zhou Chuan
Published: July 2005

Summary In the evaluation of diagnostic accuracy of tests, a gold standard on the disease status is required. However, in many complex diseases, it is impossible or unethical to obtain such a gold standard. If an imperfect standard is used, the estimated accuracy of the tests would be biased. This type of bias is called imperfect gold standard bias. In this article we develop a nonparametric maximum likelihood method for estimating ROC curves and their areas of ordinal‐scale tests in the absence of a gold standard. Our simulation study shows that the proposed estimators for the ROC curve areas have good finite‐sample properties in terms of bias and mean squared error. Further simulation studies show that our nonparametric approach is comparable to the binormal parametric method, and is easier to implement. Finally, we illustrate the application of the proposed method in a real clinical study on assessing the accuracy of seven specific pathologists in detecting carcinoma in situ of the uterine cervix.
Statistical Aspects in Physical Mapping Application to the Genome of O. oeni Strain GM
Authors: Gonçalves Luzia , Zé‐Zé Líbia , Pinheiro Hildete Prisco , Amaral‐Turkman Maria Antónia
Published: July 2005

Summary This work addresses issues around physical maps, in particular, for circular genomes. The overlapping relationship between two fragments obtained by applying two different restriction enzymes, separately, is classified as nonoverlapping, partial overlapping, and total overlapping. A double partial overlapping can also appear in a particular situation. Taking into account DNA fragment lengths and under the assumption that the left‐hand endpoints of the two restriction fragments are independent random variables, each of which with a uniform distribution along a circular genome, we present expressions for prior probabilities of those events. This information is combined with hybridization data via Bayes' theorem, in order to evaluate corresponding posterior probabilities. Additionally, we explore a sensitivity analysis to quantify the effect of length variation in the results.
Analyzing Multi‐environment Variety Trials Using Randomization‐Derived Mixed Models
Authors: Caliński T. , Czajka S. , Kaczmarek Z. , Krajewski P. , Pilarczyk W.
Published: July 2005

Summary Of interest is the analysis of results of a series of experiments repeated at several environments with the same set of plant varieties. Suppose that the experiments, multi‐environment variety trials, are all conducted in resolvable incomplete block (IB) designs. Following the randomization approach adopted in Caliński and Kageyama (2000, Lecture Notes in Statistics, 150), two models for analyzing such trial data can be considered. One is derived under a complete additivity assumption, the other takes into account possible different responses of the varieties to variable environmental conditions. The analysis under the first, the standard model, does not provide answers to questions related to the performance of the individual varieties at different environments. These can be considered when using the more general second model. The purpose of this article is to devise interesting parameter estimation and hypothesis testing procedures under that more realistic model. Its application is illustrated by a thorough analysis of a set of data from a winter wheat series of trials.
Bootstrap Tests for Overdispersion in a Zero‐Inflated Poisson Regression Model
Authors: Jung Byoung Cheol , Jhun Myoungshic , Lee Jae Won
Published: July 2005

Summary Ridout, Hinde, and Demétrio (2001, Biometrics57, 219–223) derived a score test for testing a zero‐inflated Poisson (ZIP) regression model against zero‐inflated negative binomial (ZINB) alternatives. They mentioned that the score test using the normal approximation might underestimate the nominal significance level possibly for small sample cases. To remedy this problem, a parametric bootstrap method is proposed. It is shown that the bootstrap method keeps the significance level close to the nominal one and has greater power uniformly than the existing normal approximation for testing the hypothesis.
Exploratory Bayesian Model Selection for Serial Genetics Data
Authors: Zhao Jing X. , Foulkes Andrea S. , George Edward I.
Published: July 2005

Summary Characterizing the process by which molecular and cellular level changes occur over time will have broad implications for clinical decision making and help further our knowledge of disease etiology across many complex diseases. However, this presents an analytic challenge due to the large number of potentially relevant biomarkers and the complex, uncharacterized relationships among them. We propose an exploratory Bayesian model selection procedure that searches for model simplicity through independence testing of multiple discrete biomarkers measured over time. Bayes factor calculations are used to identify and compare models that are best supported by the data. For large model spaces, i.e., a large number of multi‐leveled biomarkers, we propose a Markov chain Monte Carlo (MCMC) stochastic search algorithm for finding promising models. We apply our procedure to explore the extent to which HIV‐1 genetic changes occur independently over time.