bluuebunny/crossref_metadata_2025 huggingface dataset:
Observational evidence for westward propagation of temperature inversions in the southeastern Arabian Sea
Authors: Shankar D. , Gopalakrishna V. V. , Shenoi S. S. C. , Durand F. , Shetye S. R. , Rajan C. K. , Johnson Z. , Araligidad N. , Michael G. S.
Published: April 2004

A warm pool forms in the southeastern Arabian Sea (SEAS) prior to the onset of the summer monsoon over India in early June; the core of this warm pool is in the Lakshadweep Sea (LS). XBT and surface salinity data collected in the LS during May‐2002–April‐2003 show that temperature inversions occur off the southwest coast of India in early December with the arrival of low‐salinity waters from the Bay of Bengal. The low‐salinity waters and the inversions propagate westward along with the downwelling Rossby waves that constitute the Lakshadweep sea‐level high; inversions occur in the western LS (∼73°E) about 40 days after they occur near the coast in the eastern LS (∼75.5°E). They disappear in April, when the Tropical Convergence Zone moves over the SEAS and the warm pool engulfs the region. Ocean dynamics and air‐sea fluxes are together responsible for the formation and westward propagation of the inversions.
Competition between acceleration and loss mechanisms of relativistic electrons during geomagnetic storms
Authors: Summers D. , Ma C. , Mukai T.
Published: April 2004

We demonstrate quantitatively that whether a geomagnetic storm results in an increase or decrease of relativistic electrons in the outer zone depends on the competition between the physical processes producing the energization and loss of electrons. We construct a simplified one‐dimensional model for the electron energy distribution incorporating electron energization by cyclotron resonant interaction with whistler‐mode chorus, and electron losses due to pitch angle scattering into the loss cone by combined plasma waves (in particular, electromagnetic ion cyclotron waves and plasmaspheric hiss). We do not include radial diffusion explicitly since the model applies to the region 3 < L < 5 where radial diffusion is expected to be weak. We treat the chorus wave amplitude and electron loss rate as model input variables and compute the solution for the electron energy distribution as the model output. The extent of the electron flux increase or decrease during the event is found to be sensitively controlled by the magnitudes of the wave amplitude and electron loss rate.
Developmental stage differences in chromatin subdomains of the β-globin locus
Authors: Kim AeRi , Dean Ann
Published: April 2004

The mammalian β-globin loci each contain a family of developmentally expressed genes, and a far upstream regulatory element, the locus control region (LCR). In adult murine erythroid cells, the LCR and the transcribed β-globin genes exist within domains of histone acetylation and RNA polymerase II (pol II) is associated with them. In contrast, the silent embryonic genes lie between these domains within hypoacetylated chromatin, and pol II is not found there. We used chromatin immunoprecipitation and real-time PCR to analyze histone modification and pol II recruitment to the globin locus in human erythroid K562 cells that express the embryonic ε-globin gene but not the adult β-globin gene. H3 and H4 acetylation and H3 K4 methylation were continuous over a 17-kb region including the LCR and the active ε-globin gene. The level of modification varied directly with the transcription of the ε-globin gene. In contrast, this region in nonerythroid HeLa cells lacked these modifications and displayed instead widespread H3 K9 methylation. pol II was also detected continuously from the LCR to the ε-globin gene. These studies reveal several aspects of chromatin structure and pol II distribution that distinguish the globin locus at embryonic and adult stages and suggest that both enhancer looping and tracking mechanisms may contribute to LCR–promoter communication at different developmental stages.
Cloned transgenic farm animals produce a bispecific antibody for T cell-mediated tumor cell killing
Authors: Grosse-Hovest Ludger , Müller Sigrid , Minoia Rosa , Wolf Eckhard , Zakhartchenko Valeri , Wenigerkind Hendrik , Lassnig Caroline , Besenfelder Urban , Müller Mathias , Lytton Simon D. , Jung Gundram , Brem Gottfried
Published: April 2004

Complex recombinant antibody fragments for modulation of immune function such as tumor cell destruction have emerged at a rapid pace and diverse anticancer strategies are being developed to benefit patients. Despite improvements in molecule design and expression systems, the quantity and stability, e.g., of single-chain antibodies produced in cell culture, is often insufficient for treatment of human disease, and the costs of scale-up, labor, and fermentation facilities are prohibitive. The ability to yield mg/ml levels of recombinant antibodies and the scale-up flexibility make transgenic production in plants and livestock an attractive alternative to mammalian cell culture as a source of large quantities of biotherapeutics. Here, we report on the efficient production of a bispecific single-chain antibody in the serum of transgenic rabbits and a herd of nine cloned, transgenic cattle. The bispecific protein, designated r28M, is directed to a melanoma-associated proteoglycan and the human CD28 molecule on T cells. Purified from the serum of transgenic animals, the protein is stable and fully active in mediating target cell-restricted T cell stimulation and tumor cell killing.
The optimal rate of chromosome loss for the inactivation of tumor suppressor genes in cancer
Authors: Komarova Natalia L. , Wodarz Dominik
Published: April 2004

Many cancers are characterized by chromosomal instability (CIN). This phenotype involves the deletion and duplication of chromosomes or chromosome parts and results in a high degree of aneuploidy. The role of CIN for cancer progression is a very important, yet unresolved question. It has been argued that CIN contributes to cancer initiation because chromosome loss can unmask a mutated tumor suppressor (TSP) gene. At the same time, CIN is costly for the cell because it destroys the genome and therefore compromises clonal expansion. Here, we use mathematical models to determine whether CIN can accelerate the generation and expansion of TSP
-/-
cells in the context of this tradeoff. Comparing cells with different degrees of CIN, we find that the emergence and growth of TSP
-/-
cells is optimized if the rate of chromosome loss is of the order of 10
-3
to 10
-2
. This result is very robust, is independent of parameter values, and coincides with experimental measures using colon cancer cell lines. However, if we consider all of the steps in the pathway, including the generation of the CIN phenotype from stable cells, then it turns out that the emergence and growth of TSP
-/-
cells is never accelerated by CIN. Therefore, CIN does not arise because it accelerates the accumulation of adaptive mutations. Instead, it arises for other reasons, such as environmental factors, and is subsequently finetuned by selection to minimize the time to further cancer progression by means of the inactivation of TSP genes.
Shirking in the Contemporary Congress: A Reappraisal
Authors: Carson Jamie L. , Crespin Michael H. , Jenkins Jeffery A. , Wielen Ryan J. Vander
Published: April 2004

This paper replicates the findings that appeared in the article “Severing the Electoral Connection: Shirking in the Contemporary Congress,” published in theAmerican Journal of Political Science(44:316–325), in which Lawrence Rothenberg and Mitchell Sanders incorporated a new research design and, contrary to all previous studies, found evidence of ideological shirking in the U.S. House of Representatives. We investigate the robustness of their results by reestimating their model with Congress-specific fixed effects and find that their results no longer hold.
How One Mistake Leads to Another: On the Importance of Verification/Replication
Authors: Ward Artemus
Published: April 2004

It is impossible to overstate the importance of doing original research based on primary source material in scientific analysis (see, for example, King 1995). Failing to consult primary sources, and by definition relying on secondary sources, can lead to incorrect analyses and mistaken conclusions. An exemplary case is the apparent mystery of whether justices strategically retire and exactly when Congress passed legislation allowing federal judges to retire with benefits upon reaching age 65. One study cited 1937 as the year and based its analysis of judicial retirement on this “fact” (Abraham 1975). Subsequent studies cited the original piece without ever checking the original data—in this case a federal statute—and “replicated” the same mistaken analyses (see Atkinson 1999). In fact, the actual year this legislation was passed was 1954. This 17-year error not only makes a significant difference in the analysis of judicial retirement decisions, but also shows the importance of verification and replication in political research.
Patient Perception of Comorbid Conditions After Acoustic Neuroma Management: Survey Results From the Acoustic Neuroma Association
Authors: Ryzenman John M. , Pensak Myles L. , Tew John M.
Published: April 2004

Objectives/Hypothesis:Based on survey results of the Acoustic Neuroma Association, the patient ratings of the most difficult aspects of acoustic neuroma management were reported and a review of the literature was made regarding comorbid conditions associated with acoustic neuroma treatment and their impact on patient quality of life.

Study Design:Cohort study of 1940 patients who were members of the Acoustic Neuroma Association.

Methods:A detailed questionnaire was mailed to 2372 members of the Acoustic Neuroma Association to identify preoperative and postoperative symptoms, complications, and long‐term effects on physical and psychosocial function. For 1940 respondents (81.8%) who reported the “most difficult aspect of the AN [acoustic neuroma] experience,” the responses were analyzed by tumor size, surgical approach, and patient age and sex. Statistical analysis was performed using SPSS software.

Results:Respondents reported that the most difficult aspect of the acoustic neuroma experience was hearing loss (25.8%), followed by facial weakness (17.9%), eye problems (10.8%), and headache (10.5%). In order of frequency, men reported hearing loss, balance problems, perioperative surgical experience, and eye and facial weakness, and women reported hearing loss, facial weakness, eye problems, and headache. Facial weakness was a morbidity more often reported for men and women who had large tumors, who were young, or who had undergone the retrosigmoid approach. Balance dysfunction was significant in patients older than 75 years of age. In patients with small tumors, headaches and balance problems were frequently reported.

Conclusion:In the large cohort study of patients with acoustic neuroma, perceptions regarding the impact of treatment illustrated why it is incumbent on physicians to understand the sentiments of patients with acoustic neuroma when counseling them and recommending optimal management strategies.
Chronological Changes of Hearing in Pediatric Patients with Large Vestibular Aqueduct Syndrome
Authors: Lai Chien‐Chung , Shiao An‐Suey
Published: April 2004

Objectives: To describe the chronologic changes of hearing in patients with large vestibular aqueduct syndrome (LVAS) and identify the prognostic factors.

Study Design: A retrospective chart‐review study.

Methods: Twelve consecutive patients with LVAS were recruited at Taipei Veterans General Hospital between July 1986 and July 2000. The records of serial pure‐tone audiogram and high‐resolution computer tomography were collected. The chronologic figures of pure‐tone average (PTA) were sketched. The investigated variables included sex, laterality and type of hearing loss (HL), size of vestibular aqueduct, and the chronologic changes and configurations of hearing. Data were analyzed statistically.

Results: The degree of HL in early childhood was from moderate to profound. The worst hearing could be estimated by the hearing level in early childhood. Sixteen of 24 ears were stable. Bilateral, chronologically stepwise‐downhill hearing occurred in only one patient (1/12) during the follow‐up period. Chronologically, high‐tone hearings were worse than those of low‐tone, but fluctuations of high‐tone hearing were smaller than those of low‐tone. The sizes of vestibular aqueduct were predictive of the density of major depression and its depth.

Conclusions: LVAS, a congenital disease, is characterized by fluctuating sensorineural HL. Most hearing at PTA remained stable at least in one ear chronologically. The standard deviation of hearing at 500 Hz was the only prognostic factor for the progression of PTA. An enlarged vestibular aqueduct affects fluctuations of hearing, but the pathogenesis of HL still remains unclear and deserves further investigations.
Laser Myringotomy versus Ventilation Tubes in Children with Otitis Media with Effusion: A Randomized Trial
Authors: Koopman Jan Pieter , Reuchlin A. G. (Nees) , Kummer Eelco E. , Boumans Leon J. J. M. , Rijntjes Evert , Hoeve L. J. (Hans) , Mulder Paul G. H. , Blom Henk M.
Published: April 2004

Objectives: Insertion of ventilation tubes in children with otitis media with effusion (OME) is an accepted and common treatment procedure. The majority of patients require general anesthesia. Although laser myringotomy can be performed in local anesthesia, evidence is lacking that this treatment modality is an alternative for tubes, and outcome predictors for laser myringotomy are not available.

Study Design: Prospective randomized trial.

Methods: We screened 1,403 children with chronic OME that were indicated for placement of ventilation tubes. In the eligible patients, we performed laser myringotomy in one ear and placed a tube in the other ear, both within the same patient. Follow‐up was scheduled each month for 6 months. Success was defined as absence of effusion or aural discharge. A logistic regression model was used with success of the therapy as binary outcome. This model was based on base‐line variables, asked for in a parent's questionnaire.

Results: Two hundred eight children received the allocated intervention, and no complications occurred. The mean closure time of the laser perforation was 2.4 weeks, and the mean patency time of the ventilation tube was 4.0 months. The mean success rate was 40% for laser and 78% for tubes. Ten known variables were found to predict middle ear status after therapy.

Conclusion: Laser myringotomy is a safe but less‐effective procedure than insertion of a ventilation tube in the treatment of chronic OME. The prognostic model enables the otolaryngologist to choose the surgical treatment for the child that benefits most: laser myringotomy or ventilation tube.
A Laryngeal Dissection Station: Educational Paradigms in Phonosurgery
Authors: Dailey Seth H. , Kobler James B. , Zeitels Steven M.
Published: April 2004

Objectives: To introduce a new tool for phonosurgical training and education. A multitude of innovations in complex laryngeal surgery has catalyzed new educational initiatives. Establishing dexterity in phonomicrosurgery is often difficult to achieve while working on patients because of the narrow margin for success. Furthermore, laryngoplastic phonosurgery and open partial laryngectomy require sophisticated knowledge of precise anatomic relationships, which can be difficult to express in images. Finally, many teaching programs do not have a high volume of these procedures, and there is a significant need to transmit this information in continuing education courses.

Study Design: Prototype design.

Methods: A laryngeal dissection station (LDS) was designed to facilitate the acquisition of high‐level procedural skill sets for both transoral and transcervical techniques.

Results: This LDS can be used in existing temporal‐bone laboratories by using cadaveric larynges. A rectangular frame supports two adjustable holders, one for the larynx and one for the examining speculum of a laryngoscope. Procedures are performed with the larynx fixed in space by a novel fixator. Variation in position and orientation of the components affords simulation of both microlaryngoscopy and open surgery. The dissection station can accommodate virtually any laryngoscope, regardless of size or shape.

Conclusions: This training apparatus should facilitate laryngeal surgical instruction in residency training and continuing medical education. This device and others like it can help establish clinical competency in laryngology, should this become necessary in future educational models of residency training and recertification.
Adaptation of the Horizontal Vestibuloocular Reflex in Pilots
Authors: Lee Moon Young , Kim Min Sun , Park Byung Rim
Published: April 2004

Objectives/Hypothesis: The vestibular function in pilots has been reported as being different to that in other, normal subjects. However, there is little evidence as to why and when this occurs, and its cause is still in doubt. The aim of this study was to evaluate changes in vestibular function in student pilots attending an elementary flight course, and in other active pilots, through the use of the slow harmonic acceleration (SHA) test and to verify the occurrence and timing of any vestibular function changes.

Study Design: Cross‐sectional and prospective group design.

Methods: The six study groups were control, student pilots before and after flight training, and three groups of active pilots classified according to flight time. Gain, phase, and symmetry of horizontal eye movements induced by sinusoidal harmonic acceleration test were investigated.

Results: There were significantly higher gain values in all active pilot groups as compared with the control group at frequencies above 0.04 Hz, and in student pilots after flight training, as compared with before training at 0.01, 0.04, and 0.08 Hz. However, there were no significant differences in gain values among the three groups of active pilots or between gain values in student pilots before flight training and those of the control group. We could not find any reliable relationship between vestibuloocular reflex (VOR) function changes and other factors such as age, height, and weight.

Conclusions: We suggest that these results might be explained by adaptations caused by VOR plasticity rather than habituation and that flight training might be responsible for the modulation of the vestibular function in pilots.
Human Cortical Motor Representation of the Larynx as Assessed by Transcranial Magnetic Stimulation (TMS)
Authors: Rödel Ralph M.W. , Olthoff Arno , Tergau Frithjof , Simonyan Kristina , Kraemer Dorit , Markus Holger , Kruse Eberhard
Published: April 2004

Objectives: To analyze characteristic features and details on motor‐evoked potentials (MEPs) of the cricothyroid and vocalis muscles from single‐pulse cortical transcranial magnetic stimulation (TMS) in normal subjects to characterize cortical motor representation of laryngeal muscles.

Study Design: Prospective, experimental investigation on healthy volunteers.

Method: MEPs of the cricothyroid and vocalis muscles elicited by cortical TMS with a figure–8‐shaped coil were investigated in two groups of six healthy subjects each, with special regard to MEP amplitude as a function of the coil position on the head surface along the interaural line.

Results: Bilateral reproducible responses of the cricothyroid and the vocalis muscles could be observed in all subjects. For the cricothyroid muscle, maximal responses were obtained at mean stimulus positions of 7.5 ± 1.4 cm (contralateral) and of 7.3 ± 1.3 cm (ipsilateral), respectively. For the vocalis muscle, we found maximal responses at mean stimulus positions of 10.3 ± 1.9 cm (contralateral) and of 9.6 ± 1.6 cm (ipsilateral), respectively. Despite a considerable overlap of these coil positions, from which reproducible MEPs could be elicited in both groups of the laryngeal muscles, statistically significant separation of the cricothyroid‐and vocalis‐associated cortical representation areas was possible.

Conclusions: Our observations point to two different cortical motor representation areas, with the cricothyroid muscle‐related area being located more medially.
Evaluation of the Medical and Surgical Treatment Of Chronic Rhinosinusitis: A Prospective, Randomised, Controlled Trial
Authors: Ragab Sameh M. , Lund Valerie J. , Scadding Glenis
Published: April 2004

Objectives: To conduct the first prospective, randomized, controlled trial evaluating and comparing the medical and surgical treatment of polypoid and nonpolypoid chronic rhinosinusitis (CRS).

Materials and Methods: Ninety patients with CRS were equally randomized either to medical or surgical therapy. All patients underwent pre‐ and posttreatment assessments of visual analogue score (VAS), the Sinonasal Outcome Test‐20 (SNOT‐20), the Short Form 36 Health Survey (SF‐36), nitric oxide (NO), acoustic rhinometry, saccharine clearance time (SCT), and nasal endoscopy. Each patient had three assessments: before starting the treatment, after 6 months, and, finally, after 1 year.

Results: Both the medical and surgical treatment of CRS significantly improved almost all the subjective and objective parameters of CRS (P < .01), with no significant difference being found between the medical and surgical groups (P > .05), except for the total nasal volume in CRS (P < .01) and CRS without polyposis (P < .01) groups, in which the surgical treatment demonstrated greater changes.

Conclusion: CRS should be initially targeted with maximal medical therapy (e.g., a 3 month course of a macrolide antibiotic, douche, and topical steroid), with surgical treatment being reserved for cases refractory to medical therapy. The presence of nasal polyps is not a poor prognostic factor for the efficacy of CRS therapy, either surgical or medical.
Effects of External Beam Radiation in the Rat Tibial Nerve after Crush, Transection and Repair, or Nerve Isograft Paradigms
Authors: Myckatyn Terence M. , Brenner Michael , Mackinnon Susan E. , Chao Clifford K. , Hunter Daniel A. , Hussussian Christopher J.
Published: April 2004

Introduction: In head and neck surgery, radiation therapy is often administered to an injured nerve. Previous studies have examined the effects of either preoperative or postoperative radiation on nerve regeneration in rodents. In these studies, histomorphometric analysis was performed up to 8 month postoperatively. Given the exceptional neuroregenerative capacity of rodents, significant differences in nerve regeneration may go undetected if nerves are evaluated at such distant postoperative time points. This study is designed with a more appropriate model and investigates the effects of radiation after three common nerve injury paradigms.

Methods: Sixty‐four Lewis rates were randomized to 8 groups corresponding to uninjured, tibial nerve crush, transection and repair, or reconstruction with isografts. Half of the animals in each of these paradigms (n = 8 per group) were treated with 10 Gy of external beam radiation to the site of nerve injury at 7 days postoperatively. On postoperative day 28, functional recovery and histomorphometric assessment was performed.

Results: For a given paradigm of nerve injury, no significant differences in nerve fiber number, neural density, neural debris, or fiber width were noted between the control and radiated groups, and radiation did not affect functional recovery.

Conclusion: Radiation had no discernible effect on nerve regeneration or functional recovery in the rodent nerve injury models studied. All assessments were made at time points suitable for detecting differences in nerve regeneration between groups. These findings suggest that administration of radiation to fields containing injured peripheral nerve is unlikely to adversely affect functional outcomes.
Bone‐Anchored Hearing Aid: Comparison of Benefit by Patient Subgroups
Authors: McLarnon Claire M. , Davison Tom , Johnson Ian J. M.
Published: April 2004

Objectives/Hypothesis: The osseointegrated bone‐anchored hearing aid, using the Branemark system, is well established and has proven benefit. The aim was to study quality of life benefits within patient subgroups using the validated Glasgow Benefit Inventory (GBI).

Study Design: Retrospective questionnaire study.

Methods: Ninety‐four consecutive patients were enrolled into the study. Mean patient age was 49 years, with a female‐to‐male ratio of 1.1:1. Patient subgroups were discharging mastoid cavities, chronic active otitis media, congenital ear problems, otosclerosis, and acoustic neuroma and other unilateral hearing losses.

Results: The response rate was 73%. The score for total benefit of bone‐anchored hearing aid fitting for the entire group was +33.3 (95% confidence interval [CI], 25–42). Glasgow Benefit Inventory scores for each subgroup were all greater than +20. The congenital atresia group scored highest with +45 (95% CI, 28–61). Variation in benefit across the subgroups has been demonstrated. Fitting of BAHA following acoustic neuroma surgery was shown to be of benefit with a score of +22.2. General benefits scored highest in all subgroups compared with physical and social benefits.

Conclusion: The study demonstrated the differences in benefit within patient subgroups. Its results can be used to give patients a predictive value at the time of preoperative counseling. The study identified congenital ear disorders as the group likely to obtain maximal benefit. Notably, for the first time, the study demonstrated the documented benefit of restoring stereo hearing to patients who have acquired unilateral hearing loss following acoustic neuroma surgery using a BAHA.
Primary Parotid Malignoma Surgery in Patients With Normal Preoperative Facial Nerve Function: Outcome and Long‐Term Postoperative Facial Nerve Function
Authors: Guntinas‐Lichius Orlando , Klussmann Jens Peter , Schroeder Ulla , Quante Gero , Jungehuelsing Markus , Stennert Eberhard
Published: April 2004

Objectives/Hypothesis: Most patients with primary parotid cancer present with normal facial nerve function. The common surgical strategy for these patients is to perform a parotidectomy with facial nerve preservation. Nevertheless, the functional outcome for the facial nerve and oncological outcome is unclear.

Study Design: Medical records of 211 patients treated from 1986 to 2000 in an university hospital were reviewed. One hundred seven patients with primary surgery for primary parotid cancer and long‐term follow‐up were analyzed retrospectively.

Methods: The characteristics, treatment, and oncological outcome were evaluated using hospital chart data. All patients with postoperative facial paresis were had follow‐up with electromyography until recovery or permanent paresis became apparent.

Results: Ninety‐one patients had a normal preoperative function. Facial nerve preservation during surgery by total parotidectomy was possible in 79 patients, whereas in 28 patients a radical parotidectomy was necessary. Otherwise, the oncological characteristics of both groups were not different. Directly after total parotidectomy, half of the patients presented a facial paresis but only two patients (2%) developed a permanent partial paresis. The 5‐year disease‐free rate and the 5‐ and 10‐year survival rates were 65%, 83%, and 54%, respectively. After radical parotidectomy, the results were not significantly different. The 5‐year disease‐free rate and the overall 5‐ and the 10‐year survival rates were 56%, 62%, and 42%, respectively.

Conclusion: Treatment of primary parotid cancer with preoperatively normal facial nerve function by standardized parotidectomy and precise microsurgical preservation of the facial nerve is often possible. This approach demonstrates favorable oncological results with a low level of long‐term facial nerve morbidity.
Woronzow Greig (1805–1865), F.R.S., and his scientific interests
Authors: Appleby J.H
Published: April 2004

In March 1998 the Royal Society acquired on loan a bust of Woronzow Greig, the eldest son of Mary Somerville by her first marriage. This paper outlines his Anglo–Russian connections, his career as a barrister and his scientific interests, before describing how the portrait bust came to be made of him.
Philately and the Royal Society II
Authors: Allibone T.E
Published: April 2004

In May 1990 I presented to the Royal Society two volumes of postage stamps portraying over 300 Fellows and Foreign Members of our Society. Some of these stamps had come from my own stamp collection, some I had purchased either in Britain or from foreign dealers, and I assembled them in the sequence of date at which each Fellow had been elected to the Society, the last being H.R.H. The Princess Royal (F.R.S., 1987) on page 59. I wrote an account of this collection in
Notes and Records
.
1
RhoBTB2 is a substrate of the mammalian Cul3 ubiquitin ligase complex
Authors: Wilkins Andrew , Ping Qinggong , Carpenter Christopher L.
Published: April 2004

Rhobtb2 is a candidate tumor suppressor located on human chromosome 8p21, a region commonly deleted in cancer. Rhobtb2 is homozygously deleted in 3.5% of primary breast cancers, and gene expression is ablated in ∼50% of breast and lung cancer cell lines. RhoBTB2 is an 83-kD, atypical Rho GTPase of unknown function, comprising an N-terminal Rho GTPase domain and two tandem BTB domains. In this report, we demonstrate that RhoBTB2 binds to the ubiquitin ligase scaffold, Cul3, via its first BTB domain and show in vitro and in vivo that RhoBTB2 is a substrate for a Cul3-based ubiquitin ligase complex. Moreover, we show that a RhoBTB2 missense mutant identified in a lung cancer cell line is neither able to bind Cul3 nor is it regulated by the ubiquitin/proteasome system, resulting in increased RhoBTB2 protein levels in vivo. We suggest a model in which RhoBTB2 functions as a tumor suppressor by recruiting proteins to a Cul3 ubiquitin ligase complex for degradation.
Renovascular disease is associated with low producer genotypes of the anti‐inflammatory cytokine interleukin‐10
Authors: George S. , Ruan X.Z. , Navarrete C. , Turner D. , Reynard M. , Sweny P. , Hamilton G. , Wheeler D.C. , Powis S.H. , Moorhead J.F. , Varghese Z.
Published: April 2004

Abstract:  Cytokines are important mediators of inflammatory and proliferative responses in disease states including atherosclerosis. Genetic variations in cytokine production could potentially influence the outcome of these responses. The aim of this study was to determine whether cytokine gene polymorphism might influence the development of atherosclerotic renal artery stenosis. Sixty‐six patients with atherosclerotic renal artery stenosis and 100 normal healthy individuals were genotyped for interleukin‐10 (IL‐10), tumor necrosis factor‐α (TNF‐α), IL‐6, and IL‐2 promoter region polymorphism. TNF‐a, TNF‐d, and IL‐10 microsatellite polymorphisms were also analyzed. The frequency of the anti‐inflammatory cytokine IL‐10 promoter (−1082 A positive) GA and AA genotypes which are associated with low production were higher in the patient group when compared to the control group. The AA‐TT‐AA homozygous genotype combination of three single‐nucleotide polymorphisms at −1082, −819, and −592 in the IL‐10 gene was also observed at a higher frequency in the patient group compared to the controls. The frequency of TNF‐α, IL‐6, and IL‐2 polymorphisms did not show any significant difference between the patient and control groups. To correlate IL‐10 genotypes with differences in IL‐10 protein expression, in vitro mRNA and protein levels were analyzed in lipopolysaccharide‐stimulated peripheral blood mononuclear cells from 22 patients with renal artery stenosis and 33 controls. Individuals genotyped as A positive at position −1082 produced lower levels of IL‐10 protein and had lower copy numbers of mRNA when compared to individuals genotyped as A negative in both patient and control groups. The increased frequency of the low producer IL‐10 promoter, −1082 A‐positive genotype in patients with renal artery stenosis, suggests that IL‐10 may protect against the development of atherosclerotic renovascular disease.
Human leukocyte antigen class II associations with systemic sclerosis in South Africans
Authors: Tikly M. , Rands A. , McHugh N. , Wordsworth P. , Welsh K.
Published: April 2004

Abstract:  Human leukocyte antigen class II typing, using polymerase chain reaction–sequence‐specific primers, was performed in 52 Black South Africans with systemic sclerosis (SSc) and 112 controls. Increased frequencies of DR2 in the overall SSc group (OR = 2.4), DRB1*0301 in the limited cutaneous SSc (lcSSc) subset (OR = 9.0), and DQB1*0301/4 in the diffuse cutaneous SSc (dcSSc) subset (OR = 9.0) were observed. Pulmonary fibrosis was associated with DRB1*11 and anti‐topoisomerase I antibodies were associated with DPB1*1301 and DRB1*15. Patients with anti‐fibrillarin antibodies (AFAs) had increased the frequencies of DRB1*1101 allele group (OR = 16) and DQB1*0603/14 (OR = 13.6). These findings provide new serological and immunogenetic data on a previously unreported population. The association of AFAs with class II alleles merits further investigation.
Identification of a MAGE‐1 peptide recognized by cytolytic T lymphocytes on HLA‐B*5701 tumors
Authors: Corbière V. , Nicolay H. , Russo V. , Stroobant V. , Brichard V. , Boon T. , van der Bruggen P.
Published: April 2004

Abstract:  ‘Cancer germline’ genes such as those of the MAGE family are expressed in many tumors and in male germline cells but are silent in normal tissues. They encode shared tumor‐specific antigens that have been used in therapeutic vaccination trials of cancer patients. We report the identification of a new MAGE‐1‐encoded peptide that is recognized by a cytolytic T‐lymphocyte (CTL) clone on human leukocyte antigen (HLA)‐B*5701. The sequence of the peptide, corresponding to position 102–112 of the MAGE‐1 protein sequence, is ITKKVADLVGF. When tumor cells expressing MAGE‐1 were transfected with HLA‐B*5701, they were lyzed by the CTL clone, indicating that the peptide is processed in tumor cells and can, therefore, be used as a target for anti‐tumoral vaccination.
A multicenter international evaluation of single‐tube amplification protocols for sequencing‐based typing of HLA‐DRB1 and HLA‐DRB3,4,5
Authors: Sayer D.C. , Whidborne R. , De Santis D. , Rozemuller E.H. , Christiansen F.T. , Tilanus M.G.
Published: April 2004

Abstract:  We have described previously a novel single‐tube polymerase chain reaction (PCR) amplification (STAmp) protocol for the efficient sequencing‐based typing (SBT) of human leukocyte antigen (HLA)‐DRB1. The PCR amplification mix includes primers to each of seven allele group‐sequence motifs. We have applied this principle to the simultaneous SBT of HLA‐DRB3, ‐DRB4, and ‐DRB5 using locus specific primers. We report here a multicenter international evaluation of the STAmp protocols performed as a component of the 13th International Histocompatibility Workshop. Identical amplification primer mixes, sequencing primers, and DNA were sent to participating laboratories. The primer mixes contained the amplification primers and the PCR buffer. Each laboratory was requested to amplify the DNA with the primer mixes and perform SBT on the resulting PCR protocols, using their own protocols, and return the typing results for analysis. The reported results indicated that the expected sequence could be obtained with a variety of PCR amplification and sequencing platforms and protocols. There were difficulties but these seemed unrelated to STAmp reagents and suggest that optimal SBT results can be obtained if bi‐directional sequencing is performed and software is used for sequence verification and editing. This indicates that SBT by STAmp can be applied in many laboratories for high‐throughput HLA‐DRB1 and HLA‐DRB3,4,5 SBT.
Polymorphisms in the TNFA gene promoter region show evidence of strong linkage disequilibrium with HLA and are associated with delayed neutrophil engraftment in unrelated donor hematopoietic stem cell transplantation
Authors: Shaw B.E. , Maldonado H. , Madrigal J.A. , Smith C. , Petronzelli F. , Mayor N.P. , Potter M.N. , Bodmer J.G. , Marsh S.G.E.
Published: April 2004

Abstract: Sustained myeloid engraftment is an important determinant of outcome in hematopoietic stem cell transplantation (HSCT). Human tumor necrosis factor (TNF)‐α is encoded by a gene,TNFA, located in the class III region of the major histocompatibility complex on chromosome 6, flanked by the human leukocyte antigen (HLA) class I and II regions. A number of polymorphisms in the promoter region of theTNFAgene have been associated with increased production of TNF‐αin vivo. Additionally, raised TNF‐α levels have been reported to have a detrimental effect on the outcome in HSCT, in particular on early complications such as acute graftvshost disease, failure to engraft, and transplant‐related mortality. There is evidence of linkage disequilibrium (LD) between TNFA promoter polymorphisms and extended HLA haplotypes. We have genotyped 73 cell lines and 189 donor/recipient pairs (undergoing HSCT) for their TNFA polymorphism, all of which had been well characterized with respect to theirHLAgenes. We found evidence of strong LD betweenHLAgenes andTNFA; however, there was also evidence for recombination events having taken place, as we found that a number of transplant pairs who were matched for their HLA haplotypes were not matched for their TNFA alleles. We analyzed early outcomes in the transplant recipients and found a significant delay in engraftment in those pairs where both donor and recipients possessed an AG allele (associated with higher TNF‐α levels). Our results suggest a functional effect of TNFA polymorphisms on myeloid engraftment in unrelated HSCT.
Tissue Doppler Properties of the Left Atrial Appendage in Patients with Mitral Valve Disease
Authors: Gurlertop Yekta , Yilmaz Mustafa , Acikel Mahmut , Bozkurt Engin , Erol M. Kemal , Senocak Huseyin , Alp Necip
Published: April 2004

Objective: The purpose of this study was to compare the left atrial appendage (LAA) tissue Doppler imaging (TDI) with the classical LAA function parameters in patients with mitral valve disease. Methods: Twenty patients who had pure mitral regurgitation (group 1), 20 patients who had pure rheumatic mitral stenosis (group 2), and 20 healthy patients (group 3) were included in this study. All the cases were sinus rhythm. In order to determine the LAA functions, LAA late filling (LAALF), and late emptying (LAALE) flow velocities and LAA fractional area change (LAAFAC) were measured. LAA tissue Doppler evaluations were obtained from the PW Doppler, which was placed on the LAA lateral wall in a transverse basal short‐axis approach. LAA late systolic (LAALSW) and late diastolic (LAALDW) wave velocities were obtained from TDI records transesophageal echocardiography (TEE). Results: There were no significant differences among groups 1, 2, and 3 in terms of age, left ventricular (LV) ejection fraction, gender, and heart rate. No differences were observed between group 1 and the control group with respect to LAALE, LAALF, and LAAFAC. LAALE velocity and LAAFAC were significantly decreased in group 2 than group 1. LV diastolic diameter was significantly greater, whereas LAALSW and LAALDW velocities were significantly decreased in group 1 compared with group 3. There were no differences between groups 1 and 2 regarding to LAALSW and LAALDW velocities. LAALE, LAALF, LAALSW, LAALDW velocities, and LAAFAC were significantly decreased in group 2 than group 3. Conclusion: The TDI method may detect the LAA systolic dysfunctions, which cannot be detected using classical methods, on tissue level in patients with mitral regurgitation. In addition, the deterioration of the LAA functions at tissue level in patients with rheumatic mitral stenosis was also detected. (ECHOCARDIOGRAPHY, Volume 21, May 2004)
Structural Complications of Native Aortic Valve Endocarditis
Authors: Kelley Glenn P. , Helmcke Frederick R. , Kerut Edmund Kenneth
Published: April 2004

(ECHOCARDIOGRAPHY, Volume 21, May 2004)
Transesophageal and Transpharyngeal Ultrasound Demonstration of Reversed Diastolic Flow in Aortic Arch Branches and Neck Vessels in Severe Aortic Regurgitation
Authors: Khanna Deepak , Sinha Ashish , Nanda Navin C. , Gupta Ritesh , Sidhu Maninder , Vengala Srinivas , Dod Harvinder S. , Ilgenli T. Fikret
Published: April 2004

In the current study, we describe an adult patient with torrential aortic regurgitation due to an aortic dissection flap interfering with aortic cusp motion, in whom a transesophageal echocardiogram with the probe positioned in the upper esophagus and transpharyngeal ultrasound examination demonstrated prominent reversed flow throughout diastole in the left subclavian, left vertebral, left common carotid, and left internal carotid arteries. Another unique finding was the demonstration of aortic valve leaflets held in the fully opened position in diastole by the dissection flap as it prolapsed into the left ventricular outflow tract, dramatically documenting the mechanism of torrential aortic regurgitation in this patient. (ECHOCARDIOGRAPHY, Volume 21, May 2004)
Parental experience of services when their child requires long‐term ventilation. Implications for commissioning and providing services
Authors: Margolan H. , Fraser J. , Lenton S.
Published: April 2004

Aims  The aims of the study were to: (1) describe the families experience of the services they receive; (2) describe the care packages associated with long‐term ventilation; and (3) identify both problems and good practice.

Setting  South West Region of England, 2001.

Methods  A cross‐sectional survey of parents whose children had been ventilated for longer than 3 months. Fifteen families were interviewed.

Results  The following issues were identified: significant delays in hospital discharge [mean duration 513 days (range 14–1460 days)]; organizational fragmentation in commissioning services (12/15); problems with supply and maintenance of equipment (10/15); significant social morbidity‐reduced family incomes, housing and social isolation (9/15); difficulties with respite care (5/15); loss of employment (9/15 mothers); and problems with access to education (12/15).

Conclusions  There were significant delays in discharge from hospital largely caused by an inability to organize and fund provision in community settings. A wide variation in provision, not related to needs, was observed between families. Effective early discharge from hospital was more likely to be achieved where community children's nursing teams were already in existence. Adequate respite care was rarely available for these families.
Prevalence and Determinants of Mastitis and Milk‐borne Zoonoses in Smallholder Dairy Farming Sector in Kibaha and Morogoro Districts in Eastern Tanzania
Authors: Mdegela R. H. , Kusiluka L. J. M. , Kapaga A. M. , Karimuribo E. D. , Turuka F. M. , Bundala A. , Kivaria F. , Kabula B. , Manjurano A. , Loken T. , Kambarage D. M.
Published: April 2004

A study was carried out to establish the prevalence and determinants of mastitis and milk‐borne zoonoses in smallholder dairy farms in Kibaha and Morogoro districts (Tanzania). A total of 57 herds comprising 114 milking cows in Kibaha and 48 herds consisting of 96 milking animals in Morogoro were included in the study. A questionnaire survey was used to assess the socio‐economic determinants of mastitis, whereas California mastitis test (CMT) and microbiological assessment of milk was carried out to establish the status of mastitis and responsible aetiological agents. Seroconversion for brucellosis was evaluated using enzyme‐linked immunosorbent assay (ELISA). Animals were also tuberculin‐tested using a single comparative intradermal method and milk samples were cultured for isolation of Mycobacterium species. Based on CMT, the cow‐based prevalence of subclinical mastitis was 82.4% in Kibaha and 62.4% in Morogoro. Of the 919‐quarter milk samples cultured, 8.2% were positive for aerobic bacteria with predominant isolates being Staphylococcus epidermidis (2.8%), Staph. aureus (1.7%), Streptococcus agalactiae (1.2%) and Staph. intermedius (1.1%). There was a strong association between CMT positivity and bacteriological isolation [relative risk (RR) = 2.60; P = 0.02]. Fungal growth was observed in 21.8% (n = 881) of the samples and the isolates were yeast (19.2%), Mucor (2.5%) and Aspergillus (0.1%). Bucket feeding of calves was associated with increased risk of a quarter being CMT positive (RR = 1.24; P = 0.000), while residual calf suckling was associated with decreased risk of positivity (RR = 0.86; P = 0.015). Earth floor was associated with increased risk of CMT positivity at quarter level (RR = 1.13; P = 0.041) and Jersey breed was identified as a risk factor to mastitis. The prevalence of bovine tuberculosis was 0.4% (n = 259) and 1.7% (n = 181) in Kibaha and Morogoro, respectively. Similarly, the prevalence of brucellosis was 1% (n = 208) in Kibaha and 1.9% (n = 104) in Morogoro. Findings from this study have demonstrated a high prevalence of subclinical mastitis and existence of health risks to milk consumers despite the low prevalence of tuberculosis and brucellosis in the study herds.
Detection of Isospora suis (Biester and Murray 1934) in Piglet Faeces – Comparison of Microscopy and PCR
Authors: Joachim A. , Ruttkowski B. , Zimmermann M. , Daugschies A. , Mundt H.‐C.
Published: April 2004

Forty‐four faecal samples from piglets (2–3 animals per group) experimentally infected with Isospora suis were examined 4, 5, 7, 10, and 11 days after infection either with a modified flotation technique followed by McMaster counting (MM), MM combined with autofluorescence microscopy of faecal smears (MM‐A), or nested‐polymerase chain reaction (PCR). PCR was the most sensitive method, detecting I. suis in 70% of the samples (MM 25%, MM‐A 52%). More positive samples were detected in the untreated and the diclazuril‐treated [15 mg/kg bodyweight (BW) once or twice, respectively] groups (10 samples per group; MM 30–40%, MM‐A 50–70%, PCR 60–90%), than in the toltrazuril‐treated (20 mg/kg BW) group (14 samples; MM 0%, MM‐A 21%, PCR 57%). Parasites could be detected in the untreated group on all days with PCR and MM‐A, while MM detected oocysts only from day 5. Autofluorescence should be used as a routine diagnostic aid for the detection of oocysts in faecal samples, while PCR, being the most sensitive technique, can be employed when large numbers of samples are examined, and in experimental setups.
Evidence of reduction of gene flow between two cytotypes of Ranunculus silerifolius Lév. (Ranunculaceae) revealed with allozyme and intersimple sequence repeat polymorphisms
Authors: MAIDELIZA TESRI , OKADA HIROSHI
Published: April 2004

Gene flow between partially reproductively isolated Otaru and Matsuyama cytotypes of Ranunculus silerifolius was revealed using allozyme polymorphisms. Otaru and Matsuyama cytotypes in the parapatric population MIX were distinguishable critically by the different alleles of the Mdh‐3 allozyme locus and the hybrids between both cytotypes shared both alleles of both cytotypes. The distribution pattern of the alleles of the Mdh‐3 locus revealed that the gene flow did not occur between cytotypes within MIX. The value of gene flow between the two cytotypes within the parapatric population MIX (i.e. 0.503) was smaller than those between allopatric populations of the same cytotype (i.e. 2.550 or 1.700). The genetic distance between cytotypes within the parapatric population MIX was larger than those between the far distant populations of the same cytotypes. Dendrograms based on the Nei's genetic distance using the variations of allozyme markers showed that Otaru and Matsuyama cytotypes formed clusters separately.