bluuebunny/crossref_metadata_2025 huggingface dataset:
Concerns over Participation in Genetic Research among Malay-Muslims, Chinese and Indians in Singapore: A Focus Group Study
Authors: Wong Mee Lian , Chia Kee Seng , Wee Sharon , Chia Sin Eng , Lee Jeannette , Koh Woon Puay , Shen Han Ming , Thumboo Julian , Sofjan Dicky
Published: October 2004

Objective: This study was aimed at exploring and comparing peoples’ concerns over donation of blood specimens for genetic research across three ethnic groups in Singapore: Malay-Muslims, Chinese and Indians. Methods: We conducted 12 focus group sessions among 98 participants with 7–10 in each group. Results: Concerns over donation of blood specimens for genetic research were diverse, with all ethnic groups expressing anxiety about breach of confidentiality, finding out that they have a disease and misuse of research for cloning. Other concerns included fear of pain, blood and needle pricks and misconceptions of adverse health effects such as weight gain from donating blood specimens. Malay-Muslims were generally concerned about the selection process, potential racial discrimination, and religious beliefs regarding blood storage while Chinese and Indians were concerned about giving blood to strangers and being inconvenienced by participating in research. Conclusion: Programmes to promote community participation in genetic research should address the diverse ethnic concerns, design ethnic-sensitive messages and involve the community.
Age at Postnatal Diagnosis of Down Syndrome in the Northern Netherlands for the Period 1981–2000
Authors: Heuterman J.S.J. , de Walle H.E.K. , Poortvliet M.C. , Bouman K. , Cornel M.C.
Published: October 2004

Background: In live-born children with Down syndrome it may be very difficult for the clinician or midwife assisting at the delivery to recognise Down syndrome in newborn babies due to varying physical appearances. Meanwhile more and more therapeutical interventions become available that should start early in life. We were interested in the age at the postnatal diagnosis of Down syndrome, and found no literature on the subject. Methods: We studied the age at the diagnosis of Down syndrome for live-born babies born in the period of 1981–2000 and registered by the European Registration of Congenital Anomalies in the northern part of The Netherlands. Results: For 289 children, data on the age at the postnatal diagnosis were available, in 70.8% of whom there was suspicion of DS on the day of birth. In 1.7% of the cases, the diagnosis was made after 1 year. Place of birth and the specialty of the health worker assisting at the delivery were associated with age at diagnosis. When the child was delivered at hospital, 96.4% of the Down syndrome cases had been diagnosed within 1 month compared to 81.3% following home delivery. Conclusion: In some cases of Down syndrome in live-born babies, the diagnosis is made only after months or a year. The diagnosis was made faster in babies born in hospital compared to those born at home.
Fluoride Varnishes in Caries Prevention
Authors: Seppä Liisa
Published: October 2004

The first fluoride varnishes were developed during the 1960s (Duraphat® sodium fluoride varnish) and 1970s (Fluor Protector® silane fluoride varnish) to prolong the contact time between fluoride and enamel. Fluoride varnishes adhere to enamel, and calcium fluoride formed after application acts as a long-term reservoir of fluoride. Currently Duraphat varnish is the most widely used topical fluoride for professional application in Europe, and the use of fluoride varnishes is increasing in the USA. Duraphat varnish has been effective in three decades of clinical studies, but the results of Fluor Protector varnish are inconclusive. The percent caries reductions found in the 1990s have generally been lower than those reported in earlier studies, probably because of the higher exposure to other preventive measures in the more recent studies. In studies comparing Duraphat varnish and APF gel, Duraphat varnish was equally or more effective than APF gel. Sealants were most effective in preventing occlusal caries. Four applications per year, or three weekly applications once a year, have been found to be effective. However, several studies have shown that two applications per year may provide comparable results. Application is fast and easy. Professional prophylaxis is not necessary, and the patient can leave immediately after the treatment. No acute toxicity has been reported after using any fluoride varnish.
A Novel Germline Mutation in the von Hippel-Lindau Gene in Patients in Kuwait
Authors: AlFadhli Suad , Salim Matra , Al-Awadi Sadiqa
Published: October 2004

Objective: To determine the germline mutation in an extended family in which 1 member was diagnosed clinically with von Hippel-Lindau (VHL) disease and to investigate 3 generations of the family. Subjects and Methods: The polymerase chain reaction-single strand conformation polymorphism sequencing techniques were used to identify the germline mutation in the VHL gene in the patient and also to study 9 other members of the extended family over 3 generations. Results: The patient and 3 other members of the family were shown to have the same mutation in the splice donor site of the first intron. The mutation was identified as IVS1 + 1 G→T. Conclusion: The findings of this study indicate the presence of VHL mutation in a Kuwaiti family with Arab parentage. It is hoped that the study would contribute to understanding the types of mutation in VHL in the Middle East. Its early detection and diagnosis would help in genetic counseling of VHL patients.
The Effect of Finite Spatial Resolution on the Measurement of Cardiac Phantom Wall Thickness in Single Photon Emission Computerized Tomographic Imaging
Authors: Ballani Nasser , Dougherty Geoff
Published: October 2004

Objective: To devise and validate a method of estimating accurately myocardial wall thickness from cardiac images acquired with single photon emission tomography (SPECT). Materials and Methods: We simulated the imaging process by convolving a spatial resolution function, experimentally determined for a clinical SPECT system, with rectangular profiles mimicking the myocardial walls for different thicknesses and separations. Wall thicknesses were estimated by fitting the resulting profiles to a linear superposition of two offset Gaussians. The method was validated by extensive computer simulation and by testing on real phantom images. Results: Accurate estimates of the wall thickness of SPECT phantoms were obtained when the estimated thickness (using fitting to Gaussians) was deconvolved with the point spread function (PSF) of the imaging system using a look-up table. Conclusions: This method is a novel method of estimating wall thickness from cardiac images. It is particularly useful for small separations (e.g. at end systole and/or towards the apex of the heart) of walls that are narrow compared to the PSF of the imaging system.
Up-Regulation of Cytoskeletal Proteins in Activated Microglia
Authors: Abd-El-Basset E.M. , Prashanth J. , Ananth Lakshmi K.V.V.
Published: October 2004

Objectives: This study investigates how the tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β) affect the morphology, organization, and expression of actin, β-actin and tubulin in microglia. Materials and Methods: Microglia cultures were prepared from neopallia of newborn mice. Immunofluorescence, immunoblotting, and ELISA studies were used. Results: When microglia are treated with TNF-α, IL-1β or a combination of both for 1–5 days, the majority change from an ameboid to a large, round and flat shape. F-actin and β-actin isoform, which are diffusely arranged throughout the cytoplasm before stimulation, are reorganized into filamentous bundles underneath and parallel to the cell membrane, which projects into many ruffles. This organization is maintained even after withdrawal of the cytokines. The dense microtubule network of tubulin in nontreated microglia becomes less dense and extends to occupy the cytoplasm of the treated microglia. Immunoblotting shows that the amount of total actin, β-actin isoform and tubulin increases in treated microglia. In addition, IL-1β and a combination of both TNF-α and IL-1β stimulate the release of IL-6 by microglia. Conclusion: This study suggests that TNF-α and IL-1β have an effect on the expression of cytoskeletal proteins similar to some extent to that of LPS. The up-regulation of actin, β-actin and tubulin may play a key role in the motility and recruitment of microglia to the area of central nervous system inflammation.
Etiology and Antibiotic Susceptibility Patterns of Community-Acquired Urinary Tract Infections in a Kuwait Hospital
Authors: Dimitrov T.S. , Udo E.E. , Emara M. , Awni F. , Passadilla R.
Published: October 2004

Objective: The aim of this study was to determine the distribution and antibiotic susceptibility patterns of bacterial strains isolated from patients with community-acquired urinary tract infections (UTIs) at the Infectious Diseases Hospital, Kuwait. Materials and Methods: The study was conducted over a 7-year period. Patient information was obtained from medical record files. Antibiotic-sensitivity testing was performed by disk diffusion. E test and double disk diffusion methods were used to study the production of extended spectrum β-lactamases. Results: Of the 14,042 urine samples processed, significant bacteriuria (>105 cfu/ml) was detected in 1,606 (11.4%). The majority (74.5%) of the isolates were from women while the remaining 25.5% were from men. The majority of infections (75%) were due to Enterobacteriaceae, coagulase-negative staphylococci (10.3%) and group B streptococci (8.7%). Among the gram-negative enteric bacilli high prevalence of resistance to ampicillin, amoxicillin/clavulanic acid, cephalothin, and trimethoprim/sulfamethoxazole was observed. Increasing resistance to ciprofloxacin and gentamicin was observed in E. coli isolates over the 7 years. Multiple resistance was detected in 53.8 and 41% of E. coli and Klebsiella spp. strains, respectively. No glycopeptide-resistant enterococci were isolated. Conclusion: This study revealed that Enterobacteriaceae were the predominant bacterial pathogen of community-acquired UTIs in Infectious Diseases Hospital, Kuwait. It also demonstrated an increasing resistance to ciprofloxacin, gentamicin and the production of extended spectrum β-lactamase among UTI pathogens in the community.
Hemostatic and Fibrinolytic Response to Nasal Desmopressin in Hemodialysis Patients
Authors: Ulusoy Sukru , Ovali Ercument , Aydin Fazil , Erem Cihangir , Ozdemir Feyyaz , Kaynar Kubra
Published: October 2004

Objective: To evaluate the effect of desmopressin (DDAVP) on hemostatic parameters during dialysis and in the interval between dialysis sessions. Subjects and Methods: Fifteen patients dialyzed twice weekly at least for 1 year and 15 healthy volunteers serving as a control group were enrolled in the study. Bleeding time, platelet count, prothrombin time, activated partial thromboplastin time, tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1), euglobulin clot lysis time, protein C, protein S, fibrinogen, D-dimer, factor V, VII, VIII, IX, X and von Willebrand factor (VWF) values were studied at the beginning, at 2 and 4 h of dialysis with and without administration of DDAVP at a dose level of 2 µg/kg intranasally. Results: After dialysis, bleeding time shortened, PAI-1 and fibrinogen levels were lower, while VWF and D-dimer levels were higher. After DDAVP administration, bleeding time, PAI-1 levels were significantly lower (p < 0.01), while tPA, factor VIII and VWF levels increased significantly (p < 0.001). Conclusion: The findings indicate that DDAVP can be used for patients on dialysis with serious bleeding.
Effect of Vitamin A against Methotrexate-Induced Damage to the Small Intestine in Rats
Authors: Yüncü Mehmet , Eralp Ayhan , Koruk Mehmet , Sari Ibrahim , Bağci Cahit , Inalöz Serap
Published: October 2004

Objective: The aim of the present study was to examine whether or not the administration of vitamin A (VA) protects against methotrexate (MTX)-induced damage to small intestinal epithelium. Materials and Methods: Sixty-three male Wistar albino rats, 10–12 weeks old, weighing 240–280 g, were divided into three groups: (1) controls, (2) rats receiving MTX treatment alone, and (3) rats receiving MTX plus VA treatment. A single dose of MTX (20 mg/kg MTX in 20 ml vehicle) was administered to the rats intraperitoneally. For MTX plus VA treated groups, retinol palmitate (VA) 5,000 IU/kg dissolved in 0.5 ml sunflower oil was administered by intragastric tube 3 days prior to MTX treatment and continued till the rats were sacrificed. The control group was treated with vehicle. Both control and MTX-alone groups were also treated with sunflower oil as a placebo. The rats were sacrificed on the 2nd, 4th and 6th day after MTX treatment. Tissue samples from the jejunum were taken for histopathological analysis. Results: MTX treatment induced villus shortening and fusion, epithelial atrophy, crypt loss, inflammatory infiltrate in the lamina propria, and goblet cell depletion. The pre- and post-treatment administration of VA decreased the severity of jejunal damage caused by MTX treatment. Conclusion: Our results confirmed that administration of VA decreased the MTX-induced damage to the small intestine. This protective effect of VA may have clinical applications in cancer chemotherapy.
Relationship between Epstein-Barr Virus-Encoded RNA Expression, Apoptosis and Lymphocytic Infiltration in Gastric Carcinoma with Lymphoid-Rich Stroma
Authors: Cho Mee-Yon , Kim Tae Heon , Yi Sang Yeop , Jung Woo Hee , Park Kwang Hwa
Published: October 2004

Objective: To investigate the association of apoptosis with apoptotic proteins and Epstein-Barr virus (EBV) expression in gastric carcinoma with lymphoid-rich stroma (GCLRS) in order to clarify the relationship between lymphocytic infiltration, EBV expression and apoptosis in gastric carcinoma. Subjects and Methods: We performed immunohistochemical stains for bcl-2, bax and in situ hybridization for EBV-encoded RNA and the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling technique using the 24 cases of GCLRS and 23 cases of gastric carcinoma with lymphoid-poor stroma (GCLPS) out of 1,635 cases of gastric carcinoma. Results: The prevalence of GCLRS was 1.47% (24/1,635). The prevalence of EBV involvement in GCLRS (79%, 19/24) was significantly higher than in GCLPS (8.7%, 2/23). Apoptosis was revealed in all cases and there was no statistical difference between GCLRS and GCLPS. Immunohistochemical expression for bcl-2 was revealed only in the cytoplasm of lymphocytes in all cases, but bax showed distinct expression in the cytoplasm of neoplastic cells in all cases. There was a significant correlation between bax expression and the apoptotic index (p < 0.05). Lymphocytic infiltration was significantly correlated with the expression of EBV (p < 0.05) but not with survival rate and apoptosis. Most of the GCLRS cases were rated as low clinical stage (stage IA or B) and seemed to have a good prognosis. Conclusions: These results support the hypothesis that EBV infection plays an important role in the tumorigenesis of GCLRS, which has a better prognosis than usual gastric adenocarcinoma although there was no significant difference in the apoptotic index between GCLRS and GCLPS.
Screening of Elevated Glucose Levels in Gingival Crevice Blood Using a Novel, Sensitive Self-Monitoring Device
Authors: Müller H.-P. , Behbehani E.
Published: October 2004

Objective: To test the feasibility of using gingival crevice blood (GCB) collected during routine periodontal examination to estimate blood glucose levels using a novel and very sensitive self-monitoring device (FreeStyle®). Subjects and Methods: Forty-six patients (20 male, 26 female; age range 12–56 years, mean age 36 ± 11 years) seeking dental treatment took part in the study. Three and 4 patients reported diabetes mellitus type 1 and 2, respectively; 24 had gingivitis, of which 22 were moderate or advanced periodontitis. Periodontal probing depth (PD) and clinical attachment loss was measured at 6 sites of every tooth present, and bleeding on probing (BOP) was recorded. A site with profuse BOP was chosen for glucose determination. Measurements in GCB were compared with those of conventional capillary fingerstick blood (CFB). Results: Sufficiently large GCB volumes provided glucometer readings in 32 cases (range 1.17–10.00 mmol/l). The CFB readings ranged between 1.39 and 11.50 mmol/l. If low amounts of crevice blood prohibited a glucometer reading, significantly lower mean numbers of sites with BOP (26 vs. 67, p < 0.001) and elevated PD ≧4 mm (2 vs. 21, p < 0.05) were seen. Agreement between the two measurements was low, the mean difference was –1.22, and limits of agreement (1.96 times the standard deviation of differences) were ±2.89 mmol/l. Conclusion: The present study failed to provide any evidence for the usefulness of GCB for testing blood glucose during routine periodontal examination.
A Unique Form of Polycythemia Associated with Minimal Change Disease
Authors: Balal Mustafa , Seyrek Neslihan , Karayaylali Ibrahim , Paydas Saime
Published: October 2004

Objective: To present a case with nephrotic syndrome due to minimal change disease and polycythemia. Clinical Presentation and Intervention: A 20-year-old female was admitted to our clinic for edema and severe proteinuria present with minimal change disease since the age of 7 years. Polycythemia was found during the last activation of nephrotic syndrome. The patient was placed on glucocorticoid therapy that caused disappearance of edema, proteinuria and polycythemia. Ten months later both hemoglobin and hematocrit levels were within normal range. Conclusion: This patient with nephrotic syndrome due to minimal change disease and polycythemia was successfully treated with glucocorticoid.
Guillain-Barré Syndrome in a Patient with Hereditary Spastic Paraparesis
Authors: Alhashel Jassim Y. , Alshubaili Asmahan F. , Montasser Ashraf , Anim T.
Published: October 2004

Objective: To report the unusual occurrence of Guillain-Barré syndrome (GBS) in a case of hereditary spastic paraparesis (HSP) and describe its effect on the preexisting clinical picture as well as the importance of early recognition and treatment. Clinical Presentation and Intervention: A 41-year-old man known to have HSP developed an acute and rapid deterioration of muscle power associated with paresthesia in both upper and lower limbs. Clinical examination revealed flaccid quadriparesis with areflexia. Nerve conduction studies were suggestive of demyelinating polyneuropathy and CSF analysis showed increased protein but no cells. The diagnosis of GBS was made in addition to HSP. The patient received intravenous immunoglobulins 20 mg/kg body weight/day for 5 days. He responded very well to the treatment clinically and neurophysiologically and thereafter, he reverted to the preexisting spastic picture of HSP. Conclusion: The peripheral demyelination with GBS was severe enough to obscure the preexisting clinical picture, but fortunately it responded very well to treatment. The clinical associations with HSP are widely variable, therefore it is very important to recognize acquired treatable causes of weakness in such patients in order to prevent an increase in disability.
Acute Liver Failure due to Hodgkin’s Lymphoma
Authors: Vardareli Eser , Dündar Emine , Aslan Vahap , Gülbaş Zafer
Published: October 2004

Objective: To describe an unusual case of acute liver failure due to Hodgkin’s lymphoma. Case Presentation and Intervention: A 37-year-old man was admitted with jaundice and abdominal distension. Physical examination showed tender hepatosplenomegaly, ascites, grade I encephalopathy, left cervical (2 × 1 cm) and axillary (1 × 1 cm) lymph nodes. The laboratory data revealed elevated serum bilirubin, transaminases, lactate dehydrogenase, and coagulation defects. Initially, primary liver disease was considered, but a liver biopsy revealed infiltration of the liver by Hodgkin’s lymphoma that was confirmed by lymph node biopsy. Hodgkin’s lymphoma was of lymphocyte depletion type. Conclusion: This case demonstrates that in the presence of lymphadenopathy involving acute liver failure, hematological malignancies should be taken into consideration. Liver and lymph node biopsies should be performed as early as possible.
Clinical and Anatomic Features of Acardiac Twins
Authors: Chanoufi Mohamed Bédis , Ben Temime Riadh , Masmoudi Aïda , Ounaïssa Kamilia , Jebnoun Sami , Abid Walid , Nsiri Rafika , Chelli Héla , Khrouf Naïma , Siala-Gaïgi Soumaya
Published: October 2004

Objective: To report 6 cases of acardiac twins, and to investigate prognostic factors that would lead to survival of the normal twin. Subjects and Methods: During a 9-year period from 1993 to 2001, 6 cases of acardiac twins out of 109,000 deliveries at the Maternity Center, Tunis, Tunisia were studied. Detailed inspection, X-rays, ultrasound and autopsies were performed. Results: Prenatal diagnosis was made in only 1 case at 33 weeks of gestation. Rudimentary cardiac tissue was observed in 2 of the 6 perfused twins, and the cephalic pole was less developed than other parts of the body. Severe agenesis or hypoplasia of the thoracoabdominal organs was commonly observed. Many limb malformations were observed, with arms the most affected. One of the pump twins was stillborn, 3 died between days 1 and 3 from respiratory distress, and 2 developed cardiac failure after birth and were treated with diuretics and digoxin, which led to a favorable outcome in only 1. The ratio of the weight of the acardiac to pump twin (TWR) ranged from 50 to 142%. Conclusion: The findings of this study indicate that acardia can be diagnosed by means of ultrasound in front of a monochorial twin pregnancy when one of the fetuses is deformed and has no cardiac activity. Heart failure and polyhydramnios, as well as a TWR greater than 50% are prognostic factors for the pump twin.
Renal Failure due to Bardet-Biedl Syndrome
Authors: Ulusoy Sukru , Kaynar Kubra , Gul Semih , Ukinc Kubilay
Published: October 2004

Objective: To describe a case of Bardet-Biedl syndrome involving renal failure and retinal dystrophy. Case Presentation and Intervention: A 50-year-old female patient presented to the emergency service with uremic symptoms and metabolic acidosis. Polydactyly, retinitis pigmentosa, obesity, strabismus, nistagmus and renal failure were found. Because she had end-stage renal failure, hemodialysis therapy was started. She has been well for 18 months, without any complication on hemodialysis. Conclusion: Bardet-Biedl syndrome should be considered in patients with polydactyly, retinitis pigmentosa and renal failure.
Mismatch repair proteins: key regulators of genetic recombination
Authors: Surtees J.A. , Argueso J.L. , Alani E.
Published: October 2004

Mismatch repair (MMR) systems are central to maintaining genome stability in prokaryotes and eukaryotes. MMR proteins play a fundamental role in avoiding mutations, primarily by removing misincorporation errors that occur during DNA replication. MMR proteins also act during genetic recombination in steps that include repairing mismatches in heteroduplex DNA, modulating meiotic crossover control, removing 3′ non-homologous tails during double-strand break repair, and preventing recombination between divergent sequences. In this review we will, first, discuss roles for MMR proteins in repairing mismatches that occur during recombination, particularly during meiosis. We will also explore how studying this process has helped to refine models of double-strand break repair, and particularly to our understanding of gene conversion gradients. Second, we will examine the role of MMR proteins in repressing homeologous recombination, i.e. recombination between divergent sequences. We will also compare the requirements for MMR proteins in preventing homeologous recombination to the requirements for these proteins in mismatch repair.
Studies on crossover-specific mutants and the distribution of crossing over in Drosophila females
Authors: Bhagat R. , Manheim E.A. , Sherizen D.E. , McKim K.S.
Published: October 2004

In Drosophila females, the majority of recombination events do not become crossovers and those that do occur are nonrandomly distributed. Furthermore, a group of Drosophila mutants specifically reduce crossing over, suggesting that crossovers depend on different gene products than noncrossovers. In mei-218 mutants, crossing over is reduced by approximately 90% while noncrossovers and the initiation of recombination remain unchanged. Importantly, the residual crossovers have a more random distribution than wild-type. It has been proposed that mei-218 has a role in establishing the crossover distribution by determining which recombination sites become crossovers. Surprisingly, a diverse group of genes, including those required for double strand break (DSB) formation or repair, have an effect on crossover distribution. Not all of these mutants, however, have a crossover-specific defect like mei-218 and it is not understood why some crossover-defective mutants alter the distribution of crossovers. Intragenic recombination experiments suggest that mei-218 is required for a molecular transition of the recombination intermediate late in the DSB repair pathway. We propose that the changes in crossover distribution in some crossover-defective mutants are a secondary consequence of the crossover reductions. This may be the activation of a regulatory system that ensures at least one crossover per chromosome, and which compensates for an absence of crossovers by attempting to generate them at random locations.
Unique invasions and resolutions: DNA repair proteins in meiotic recombination in Drosophila melanogaster
Authors: Blanton H. , Sekelsky J.
Published: October 2004

To ensure the accurate disjunction of homologous chromosomes during meiosis, most eukaryotes rely on physical connections called chiasmata, which form at sites of crossing over. In the absence of crossing over, homologs may segregate randomly, resulting in high frequencies of aneuploid gametes. The process of meiotic recombination poses unique problems for the cell that must be overcome to ensure normal disjunction of homologous chromosomes. How is it ensured that crossovers occur between homologous chromosomes, rather than between sister chromatids? What determines the number and location of crossovers? The functions of DNA repair proteins hold some of the answers to these questions. In this review, we discuss DNA repair proteins that function in meiotic recombination in Drosophila melanogaster. We emphasize the processes of strand invasion and Holliday junction resolution in order to shed light on the questions raised above. Also, we compare the variety of ways several eukaryotes perform these processes and the different proteins they require.
A role for the MutL homologue MLH2 in controlling heteroduplex formation and in regulating between two different crossover pathways in budding yeast
Authors: Abdullah M.F.F. , Hoffmann E.R. , Cotton V.E. , Borts R.H.
Published: October 2004

Background and aims: Mismatch repair proteins play important roles during meiotic recombination in the budding yeast Saccharomyces cerevisiae and most eukaryotic organisms studied to date. To study the functions of the mismatch repair protein Mlh2p in meiosis, we constructed mlh2Δ strains and measured rates of crossing over, gene conversion, post-meiotic segregation and spore viability. We also analysed mlh1Δ, mlh3Δ, msh4Δ, msh5Δ, exo1Δ and mus81Δ mutant strains singularly and in various combinations. Results: Loss of MLH2 resulted in a small but significant decrease in spore viability and a significant increase in gene conversion frequencies but had no apparent effect on crossing over. Deletion of MLH2 in mlh3Δ, msh4Δ or msh5Δ strains resulted in significant proportion of the “lost” crossovers found in single deletion strains being regained in some genetic intervals. We and others propose that there are at least two pathways to generate crossovers in yeast (Ross-Macdonald and Roeder, 1994; Zalevsky et al., 1999; Khazanehdari and Borts, 2000; Novak et al., 2001; de los Santos et al., 2003). Most recombination intermediates are processed by the “major”, Msh4-dependent pathway, which requires the activity of Mlh1p/Mlh3p/Msh4p/Msh5p as well as a number of other proteins. The minor pathway(s) utilizes Mms4p/Mus81p. We suggest that the absence of Mlh2p allows some crossovers from the MSH4 pathway to traverse the MUS81-dependent pathway.
Homologous recombinational repair proteins in mouse meiosis
Authors: Bannister L.A. , Schimenti J.C.
Published: October 2004

Eukaryotic meiotic recombination requires numerous biochemical processes, including break initiation, end resection, strand invasion and heteroduplex formation, and, finally, crossover resolution. In this review, we discuss primarily those proteins involved in the initial stages of homologous recombination, including SPO11, MRE11, RAD50, NBS1, DMC1, RAD51, RAD51 paralogs, RAD52, RPA, RAD54, and RAD54B. Focusing on the mouse as a model organism, we discuss what is known about the conserved roles of these proteins in vertebrate somatic cells and in mammalian meiosis. We consider such information as gene expression in gonadal tissue, protein localization patterns on chromosomal cores in meiocyte nuclei, and information gleaned from mouse models.
Roles of RecA homologues Rad51 and Dmc1 during meiotic recombination
Authors: Shinohara A. , Shinohara M.
Published: October 2004

RecA protein is involved in homology search and strand exchange processes during recombination. Mitotic cells in eukaryotes express one RecA, Rad51, which is essential for the repair of double-strand breaks (DSBs). Additionally, meiotic cells induce the second RecA, Dmc1. Both Rad51 and Dmc1 are necessary to generate a crossover between homologous chromosomes, which ensures the segregation of the chromosomes at meiotic division I. It is largely unknown how the two RecAs cooperate during meiotic recombination. In this review, recent advances on our knowledge about the roles of Rad51 and Dmc1 during meiosis are summarized and discussed.
Inter-sex variation in synaptonemal complex lengths largely determine the different recombination rates in male and female germ cells
Authors: Tease C. , Hultén M.A.
Published: October 2004

Meiotic chromosomes in human oocytes are packaged differently than in spermatocytes at the pachytene stage of meiosis I, when crossing-over takes place. Thus the meiosis-specific pairing structure, the synaptonemal complex (SC), is considerably longer in oocytes in comparison to spermatocytes. The aim of the present study was to examine the influence of this length factor on meiotic recombination in male and female human germ cells. The positions of crossovers were identified by the DNA mismatch repair protein MLH1. Spermatocytes have approximately 50 crossovers per cell in comparison to more than 70 in oocytes. Analyses of inter-crossover distances (and presumptively crossover interference) along SCs suggested that while there might be inter-individual variation, there was no consistent difference between sexes. Thus the higher rate of recombination in human oocytes is not a consequence of more closely spaced crossovers along the SCs. The rate of recombination per unit length of SC is higher in spermatocytes than oocytes. However, when the so-called obligate chiasma is excluded from the analysis, then the rates of recombination per unit length of SC are essentially identical in the two sexes. Our analyses indicate that the inter-sex difference in recombination is largely a consequence of the difference in meiotic chromosome architecture in the two sexes. We propose that SC length per se, and therefore the size of the physical platform for crossing-over (and not the DNA content) is the principal factor determining the difference in rate of recombination in male and female germ cells. A preliminary investigation of SC loop size by fluorescence in situ hybridization (FISH) indicated loops may be shorter in oocytes than in spermatocytes.
Novel and diverse functions of the DNA mismatch repair family in mammalian meiosis and recombination
Authors: Kolas N.K. , Cohen P.E.
Published: October 2004

The mismatch repair (MMR) family is a highly conserved group of proteins that function in genome stabilization and mutation avoidance. Their role has been particularly well studied in the context of DNA repair following replication errors, and disruption of these processes results in characteristic microsatellite instability, repair defects and, in mammals, susceptibility to cancer. An additional role in meiotic recombination has been described for several family members, as revealed by extensive studies in yeast. More recently, the role of the mammalian MMR family in meiotic progression has been elucidated by the phenotypic analysis of mice harboring targeted mutations in the genes encoding several MMR family members. This review will discuss the phenotypes of the various mutant mouse lines and, drawing from our knowledge of MMR function in yeast meiosis and in somatic cell repair, will attempt to elucidate the significance of MMR activity in mouse germ cells. These studies highlight the importance of comparative analysis of MMR orthologs across species, and also underscore distinct sexually dimorphic characteristics of mammalian recombination and meiosis.
Meiotic recombination intermediates and mismatch repair proteins
Authors: Hoffmann E.R. , Borts R.H.
Published: October 2004

Mismatch repair proteins are a highly diverse group of proteins that interact with numerous DNA structures during DNA repair and replication. Here we review data for the role of Msh4, Msh5, Mlh1, Mlh3 and Exo1 in crossing over. Based on the paradigm of interactions developed from studies of mismatch repair, we propose models for the mechanism of crossover implementation by Msh4/Msh5 and Mlh1/Mlh3.
Cytological studies of meiotic recombination in human males
Authors: Hassold T. , Judis L. , Chan E.R. , Schwartz S. , Seftel A. , Lynn A.
Published: October 2004

We combined immunostaining and fluorescence in situ hybridization (FISH) methodology to directly examine meiotic exchanges in over 2,000 pachytene stage spermatocytes from 25 individuals. Our results indicate that, on average, there are about 50 exchanges per cell and that, with the exception of the acrocentric chromosomes, all chromosome arms harbor at least one exchange. We also identified significant among-individual variation in the mean number of exchanges, with an approximate 20% difference between individuals with “low” and those with “high” exchange frequencies.
The mammalian mid-pachytene checkpoint: meiotic arrest in spermatocytes with a mutation in Atm alone or in combination with a Trp53 (p53) or Cdkn1a (p21/cip1) mutation
Authors: Ashley T. , Westphal C. , Plug-de Maggio A. , de Rooij D.G.
Published: October 2004

ATM, the protein product of the gene mutated in the human autosomal recessive disorder ataxia telangiectasia, is involved in detection of double strand breaks (DSBs) and is a key component of the damage surveillance network of cell cycle proteins. In somatic cells ATM phosphorylates many other proteins including p53, an important regulator of cell cycle control. Mice deficient for Atm are male sterile with arrest and apoptosis occurring at testis epithelial stage IV, which in normal spermatocytes corresponds to mid-pachynema. Unlike the situation in somatic cells, we find no evidence that disruption of the Trp53 (p53) gene, or its down-stream target Cdkn1a (p21/Cip1) results in even a partial rescue of the Atm defect.
Rare Infiltrative Lung Diseases: A Challenge for Clinicians
Authors: Poletti Venerino , Costabel Ulrich , Casoni Gian Luca , Bigliazzi Caterina , Drent Marjolein , Olivieri Dario
Published: October 2004

Rare diffuse infiltrative lung diseases are a challenge for clinicians, radiologists, and pathologists for at least three reasons: (a) their low incidence and prevalence hamper the acquisition of expertise and frequently the diagnosis is delayed; (b) therapeutic actions are mainly empirical and based on steroid use, and (c) pathogenetic events are difficult to explain and only recently new therapeutic measures taking advantage of innovative genetic and/or immunopathogenetic studies have been suggested. In this review rare diffuse lung disorders are briefly discussed (pulmonary alveolar proteinosis, inherited lipidoses, acute eosinophilic pneumonia, amyloidosis, pulmonary ossification, pulmonary alveolar microlithiasis). The list is obviously not exhaustive and arbitrarily chosen. The intent is, however, to emphasize that in this difficult field multidisciplinary expertise and the knowledge of the most recent pathogenetic mechanisms have the main role in diagnosis and treatment.
Impact of Spiral Computed Tomography on the Diagnosis of Pulmonary Embolism in a Community Hospital Setting
Authors: Ost David , Khanna Dheeraj , Shah Rakesh , Hall Charles S. , Shah Suketu , Lesser Martin , Fein Alan M.
Published: October 2004

Background: While the optimal role of spiral CT angiography (CTA) in the diagnosis of pulmonary embolism (PE) remains controversial, this technology is already being widely utilized in the community setting. Objectives: To assess the impact CTA has had on angiography utilization rates and the overall diagnostic rate of PE. Methods: All patients evaluated for PE during a 4-year period were studied. PE was defined as either a high-probability V/Q scan, a positive conventional angiogram, or a CTA with emboli in the segmental or larger pulmonary vessels. Diagnostic rates of PE per 1,000 hospital admissions were determined and analyzed for time periods before and after the introduction of CTA. CT reports were compared with their concurrent chest radiograph (CXR) reports and additional findings that were not apparent on CXR were abstracted. Results: The diagnostic rate of PE per 1,000 hospital admissions was 1.8 prior to the introduction of CTA and increased to 2.8 per 1,000 admissions after the introduction of CTA (p < 0.0001). Total costs for diagnostic testing per PE diagnosis made went from $2,518 to $2,572. While the number of PE diagnosed by V/Q scan remained constant, the number of PE diagnosed by conventional angiography decreased while the number diagnosed by CTA increased. In patients with intermediate probability V/Q scan results, the percentage of patients receiving subsequent angiography (conventional or CTA) increased from 17 to 26% (p = 0.043). When conventional angiography was performed, CT imaging of the chest still had to be ordered for other reasons 38% of the time. Additional information was obtained in 78% of cases when CTA was performed. Conclusions: Increased utilization of CTA was associated with an increase in angiography utilization rates and diagnostic rates of PE, was cost effective, and often provided additional, useful, and unanticipated diagnostic information.
Evolving Differences in the Presentation of Severe Asthma Requiring Intensive Care Unit Admission
Authors: Han Paul , Cole Randolph P.
Published: October 2004

Background: The prevalence of asthma in the community has been increasing. Asthma mortality has not followed the same pattern. Patients who present with a severe asthma exacerbation share many characteristics with patients who die from asthma. Objective: We examined the differences in the presentation of severe asthma in adults admitted to a medical intensive care unit (MICU) over a 10-year interval. Methods: We reviewed the records of the MICU at the Columbia Presbyterian Medical Center for all admissions with severe asthma for the period from January 2000 to December 2001. The data collected included the number of admissions per month, baseline characteristics, initial arterial pH and PCO2, length of ICU stay, and complications. These data were compared with similar data obtained over the period 1990–1991. Results: The number of MICU admissions per month for severe asthma decreased from 3.1 in 1990–1991 to 0.8 in 2000–2001. There was a trend toward a reduction in asthma severity as determined by a decrease in the initial arterial PCO2 from 80 ± 27 to 55 ± 23 mm Hg and an increase in pH from 7.1 ± 0.14 to 7.23 ± 0.14 (0.10 > p > 0.05 for both). There was 1 death from severe hypoxemia and respiratory acidosis in the earlier series and no asthma deaths in the later series. Conclusion: In our institution, there has been a decline in the number of patients with status asthmaticus requiring ICU admission over the past 10 years and a trend towards less advanced presentations with reduced levels of respiratory acidosis and decreased ICU length of stay. These changes may be related to improved medications, education, or access to care in the community.
Exhaled Nitric Oxide and Hydrogen Peroxide Concentrations in Asthmatic Smokers
Authors: Horváth Ildikó , Donnelly Louise E. , Kiss András , Balint Beata , Kharitonov Sergei A. , Barnes Peter J.
Published: October 2004

Background: Cigarette smoking is associated with decreased nitric oxide (NO) production and increased oxidative stress in the airways. Exhaled NO levels are not higher in asthmatic smokers than in healthy non-smokers, and the value of exhaled NO for diagnosing asthma in smokers has been questioned. Objectives: To compare exhaled NO concentrations between healthy and steroid-naive and steroid-treated asthmatic smokers and non-smokers. To also assess the acute effect of cigarette smoking on exhaled NO and hydrogen peroxide (H2O2) levels in asthmatic smokers. Methods: Exhaled NO was measured by chemiluminescence and exhaled H2O2 spectrophotometrically. In 7 steroid-naive asthmatic smokers exhaled NO and H2O2 was measured both before and 15 min after smoking one cigarette. Data are given as median (range). Results: Exhaled NO level was significantly higher in steroid-naive asthmatic smokers than in healthy smokers [7.7 (3.4–32.5) ppb vs. 3.2 (2.0–7.2) ppb, p < 0.001]. Exhaled NO values were lower in smokers than in non-smokers both in healthy subjects and in steroid-naive asthmatic patients. Steroid-treated asthmatic smokers had a tendency for lower exhaled NO values [5.4 (1.7–12.0) ppb] compared to steroid-naive asthmatic smokers. Cigarette smoking caused an acute increase in exhaled H2O2 concentrations together with a decrease in exhaled NO concentration. Conclusions: Our data suggest that an elevation in exhaled NO concentration is associated with asthma in smokers. This difference may be useful for diagnosing the disease in smokers, but its clinical value needs further evaluation. Acute increase in exhaled H2O2 concentrations suggests that smoking increases the oxidative stress in the asthmatic airways.
Low Incidence of Paradoxical Bronchoconstriction with Bronchodilator Drugs Administered by Respimat® Soft Mist™ Inhaler: Results of Phase II Single-Dose Crossover Studies
Authors: Koehler D. , Pavia D. , Dewberry H. , Hodder R.
Published: October 2004

Background and Objectives: Respimat® Soft Mist™ Inhaler (SMI) is an innovative device that offers improved lung deposition and is an environmentally friendly alternative to conventional, chlorofluorocarbon-containing metered-dose inhalers (CFC-MDIs). The aqueous formulations of bronchodilator drugs administered from Respimat SMI contain low concentrations of ethylene diamine tetra-acetic acid (EDTA), a stabilising agent, and benzalkonium chloride (BAC), an antibacterial agent, both of which have been associated with bronchoconstriction when administered via nebulisers. The aim of this retrospective analysis was to compare the incidence of paradoxical bronchoconstriction with bronchodilator drugs administered via Respimat SMI or a CFC-MDI in patients with asthma or chronic obstructive pulmonary disease (COPD). Methods: Nine randomised, active- and/or placebo-controlled, double-blind, crossover studies, in which asthmatic and COPD patients (n = 444 and n = 216, respectively) received a β2-agonist and/or anticholinergic or placebo via Respimat SMI or CFC-MDI, were included in the analysis. The incidence of conditions indicative of paradoxical bronchoconstriction were collated and divided into four categories: (1) ‘bronchospasm’; (2) two or more of the following events: ‘other respiratory adverse events’, ‘rescue medication use’ or ‘asymptomatic drop in forced expiratory volume in one second’ (FEV1); (3) either ‘rescue medication use’ or ‘other respiratory adverse event’; (4) ‘asymptomatic drop in FEV1’. Results: The incidence of adverse events indicative of paradoxical bronchoconstriction was low in those patients using the Respimat SMI device, and similar to that seen in the CFC-MDI group. In addition, the incidence of adverse events indicative of paradoxical bronchoconstriction observed in the Respimat SMI group was similar for BAC + EDTA and BAC-only drug formulations. Conclusions: These studies demonstrate that, due to the extremely low absolute amounts of BAC and EDTA delivered to the lungs by the device, Respimat SMI is safe with regard to paradoxical bronchoconstriction in patients with asthma or COPD.
Effects of Isolated Cycle Ergometer Training on Patients with Moderate-to-Severe Chronic Obstructive Pulmonary Disease
Authors: Pitta F. , Brunetto A.F. , Padovani C.R. , Godoy I.
Published: October 2004

Background: Pulmonary rehabilitation (PR) programs are beneficial to patients with chronic obstructive pulmonary disease (COPD), and lower-extremity training is considered a fundamental component of PR. Nevertheless, the isolated effects of each PR component are not well established. Objective: We aimed to evaluate the effects of a cycle ergometry exercise protocol as the only intervention in a group of COPD patients, and to compare these results with a control group. Methods: 25 moderate-to-severe COPD patients were evaluated regarding pulmonary function, respiratory muscle strength, exercise capacity, quality of life and body composition. Patients were allocated to one of two groups: (a) the trained group (TG; n = 13; 6 men) was submitted to a protocol of 24 exercise sessions on a cycle ergometer, with training intensity initially set at a heart rate (HR) close to 80% of maximal HR achieved in a maximal test, and load increase based on dyspnea scores, and (b) the control group (CG; n = 12; 6 men) with no intervention during the protocol period. Results: TG showed within-group significant improvements in endurance cycling time, 6-min walking distance test, maximal inspiratory pressure and in the domain ‘dyspnea’ related to quality of life. Despite the within-group changes, no between-group significant differences were observed. Conclusion: In COPD patients, the results of isolated low-to-moderate intensity cycle ergometer training are not comparable to effects of multimodality and high-intensity training programs.