bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potentiation of in vitro ara‐C cytotoxicity by ribonucleotide reductase inhibitors, cyclin‐dependent kinase modulators and the DNA repair inhibitor aphidicolin in paediatric acute myeloid leukaemia
Authors: Hubeek I. , Peters G. J. , Broekhuizen A. J. F. , Sargent J. , Gibson B. E. S. , Creutzig U. , Kaspers G. J. L. 
Published: September 2005

SummaryTo modulate in vitro cytarabine (ara‐C) resistance we combined ara‐C with six potential resistance modifiers in 10 paediatric acute myeloid leukaemia (AML) patient samples (methyl thiazol tetrazolium assay). Drug interactions were determined by median drug effect analysis. Co‐incubation of ara‐C/aphidicolin showed strong synergism. The combinations of ara‐C/cladribine and ara‐C/gemcitabine were synergistic. Nearly additive and moderately synergistic interactions were observed between ara‐C/flavopiridol and ara‐C/UCN‐01. The combination of ara‐C/decitabine was antagonistic. In conclusion, favourable interactions were observed between ara‐C and aphidicolin, cladribine, gemcitabine and also with flavopiridol and UCN‐01, supporting the evaluation of these combinations in clinical trials with AML patients.
Cytomorphological study of soft tissue neoplasms: role of fluorescent immunocytochemistry in diagnosis
Authors: Rekhi B. , Bhatnagar D. , Bhatnagar A. , Saxena S. 
Published: September 2005

Objectives:  Exact categorization of soft tissue tumours (STTs) on smears requires application of various ancillary techniques. This study was aimed at evaluating the role of fluorescent immunocytochemistry (FICC) in cyto‐diagnosis of 30 STT cases.Methods:  Thirty cases of soft tissue tumours were included in the present study. All cases were subjected to routine Giemsa and Papanicolaou stain. Extra smears were made and kept for fluorescent immunostaining. A panel of cytoskeletal antibodies, tagged with FITC (Fluorescein isothyocynate), was employed in all these cases. Fluorescent immunostained smears were examined under Zeiss Confocal Laser scanning microscope, using double immunofluorescence (red‐green). Finally, all cases were subjected to biopsy and again immunoperoxidase staining.Results:  Among the 30 cases in the present study, unaided cytological diagnoses ranged from ‘spindle cell’ tumour in four (13.3%) cases, benign and malignant spindle cell tumour in 17 (56.6%) cases, to malignant mesenchymal tumour in nine (30%) cases. FICC helped in further correct categorization of 25/30 (83.3%) cases viz. leiomyoma (three), benign neurogenic tumour (six), schwannoma (one), dermatofibrosarcoma protuberans (three), synovial sarcoma (two), rhabdomyosarcoma (two), malignant fibrous histiocytoma (five) and malignant peripheral nerve sheath tumour (three). Aggressive fibromatosis was found to be a missed diagnosis in two cases. Overall concordance between cyto‐diagnosis with FICC, and histopathology results was 83.3% (P < 0.05).Conclusion:  Fluorescent immunocytochemistry is a significant ancillary technique for making a rapid and specific diagnosis of STT, as required for their timely management. Incorporation of a wide panel of antibody markers with clinico‐cytological correlation is recommended in forming an exact diagnosis in these cases.
Mesonephric hyperplasia can cause abnormal cervical smears: report of three cases with review of literature
Authors: Hejmadi R. K. , Gearty J. C. , Waddell C. , Ganesan R. 
Published: September 2005

Background:  Hyperplastic mesonephric remnants are an incidental finding in occasional uterine or cervical surgical specimens. We describe three cases in which such remnants were postulated to be the source of abnormal glandular cells in cervical smears.Cases:  In all three cases abnormal glandular cells were seen in cervical smears. Subsequent histology showed the presence of hyperplastic mesonephric remnants that communicated with the endocervical canal and were likely to be the source of the abnormal glandular cells. We believe that the key features of these cells, which may aid their distinction from other causes of glandular abnormalities, are their loose clustering, lack of significant anisocytosis and cuboidal outlines.Conclusion:  We aim to document mesonephric hyperplasia as a possible source for abnormal glandular cells in cervical smears.
Utility and diagnostic accuracy of fallopian tube touch imprint cytology
Authors: Aali B. S. , Malekpour R. , Nakheii N. , Mehdizadeh A. 
Published: September 2005

Objective:  To determine the diagnostic accuracy of cytology smears in distinguishing between tube and non‐tube structures.Methods:  One hundred cytology smears of fallopian tube and non‐tube structures (vessels, round and ovarian ligaments) were prepared from surgically removed uterus and fallopian tube specimens and stained by the Papanicolaou method. The slides were reviewed blindly by pathologists and interpreted as tube or non‐tube structures. The results were compared to the histological examination of the same specimens.Findings:  Results indicated an overall accuracy of 97% with a specificity of 98% and sensitivity of 96% for cytology smears, taking histology as the gold standard. Positive and negative predictive values were 96.1% and 97.9%, respectively.Conclusion:  Cytology smears are a convenient and cost effective tool for laboratory confirmation of tubal sterilization. This method can reduce the costs of laboratory examination, especially in developing countries, where tubal sterilizations are done in large cohorts. However, histological slides remain the gold standard in cases of medicolegal problems.
Increased expression of 11β‐hydroxysteroid dehydrogenase type 1 in type 2 diabetic myotubes
Authors: Abdallah B. M. , Beck‐Nielsen H. , Gaster M. 
Published: September 2005

AbstractBackground  Alterations in glucocorticoid hormone metabolism in skeletal muscle have been suggested to contribute to the pathogenesis of the metabolic syndrome. Circulating glucocorticoids consist of inactive cortisone and active cortisol interconverted in various tissues by the enzyme 11β hydroxysteroid dehydrogenase (HSD). This study aims to investigate whether human myotubes established from healthy obese and matched obese type 2 diabetic (T2D) subjects reveal differences in the expression level of glucocorticoid receptor (GR) and 11β hydroxysteroid dehydrogenase (HSD1 and HSD2), and to investigate whether chronic exposure to cortisone affects glucose transport.Methods  In myotubes established from T2D and healthy control subjects we determined the mRNA expression of HSD1, HSD2, GR and determined basal and insulin‐stimulated glucose uptake in myotubes precultured with cortisone, cortisol and the HSD1 inhibitor, carbenoxolone for four days.Results  Myotubes established from T2D subjects showed an increased expression of HSD1 mRNA, but with no differences in mRNA of GRα, LXRα and LXRβ, whereas HSD2 mRNA was not expressed. Cortisone reduced glucose uptake in diabetic myotubes and the cortisone effect could be abolished by the HSD1 inhibitor carbenoxolone.Conclusions  Our study shows that cortisone reduces glucose uptake in diabetic myotubes and that this effect seems mediated by an increased mRNA HSD1 expression emphasizing that the local conversion of inactive to active glucocorticoids may be important in the pathogenesis of insulin resistance.
High prevalence of vasomotor reflex impairment in newly diagnosed leprosy patients
Authors: Illarramendi X. , Bührer‐Sékula S. , Sales A. M. , Bakker M. I. , Oliveira A. , Nery J. A. C. , Oskam L. , Wilder‐Smith A. , Sampaio E. P. , Sarno E. N. 
Published: September 2005

AbstractBackground  Initial nerve damage in leprosy occurs in small myelinated and unmyelinated nerve fibers. Early detection of leprosy in the peripheral nervous system is challenging as extensive nerve damage may take place before clinical signs of leprosy become apparent.Patients and methods  In order to determine the prevalence of, and factors associated with, peripheral autonomic nerve dysfunction in newly diagnosed leprosy patients, 76 Brazilian patients were evaluated prior to treatment. Skin vasomotor reflex was tested by means of laser Doppler velocimetry. Blood perfusion and reflex vasoconstriction following an inspiratory gasp were registered on the second and fifth fingers.Results  Vasomotor reflex was impaired in at least one finger in 33/76 (43%) patients. The fifth fingers were more frequently impaired and suffered more frequent bilateral alterations than the second fingers. Multivariate regression analysis showed that leprosy reaction (adjusted odds ratio = 8·11, 95% confidence interval: 1·4–48·2) was associated with overall impaired vasomotor reflex (average of the four fingers). In addition, palmar erythrocyanosis and an abnormal upper limb sensory score were associated with vasomotor reflex impairment in the second fingers, whereas anti‐phenolic glycolipid‐I antibodies, ulnar somatic neuropathy and a low finger skin temperature were associated with impairment in the fifth fingers.Conclusions  A high prevalence of peripheral autonomic dysfunction as measured by laser Doppler velocimetry was observed in newly diagnosed leprosy patients, which is clinically evident late in the disease. Autonomic nerve lesion was more frequent than somatic lesions and was strongly related to the immune‐inflammatory reaction against M. leprae.
Gender‐specific expression of liver organic anion transporters in rat
Authors: Rost D. , Kopplow K. , Gehrke S. , Mueller S. , Friess H. , Ittrich C. , Mayer D. , Stiehl A. 
Published: September 2005

AbstractBackground  Sex differences in drug pharmacokinetics have been well recognized and gender has been considered a risk factor for adverse events to medications. The aim of this study was to investigate the effect of gender on the expression of hepatocellular transport proteins involved in uptake and secretion of organic anions in rat.Materials and methods  Expression of the rat liver organic anion transporting polypeptides (Oatps) and multidrug resistance proteins (Mrps) was analysed by reverse transcription polymerase chain reaction (RT‐PCR), immunoblot analysis and immunofluorescence microscopy in male and female rats. Regulation of these transport proteins in response to the steroid dehydroepiandrosterone (DHEA) was investigated.Results  In untreated rats, protein expression significantly differed between genders being higher (Mrp2, Mrp3), comparable [Oatp1a1 (Oatp1); Oatp1b2 (Oatp4)] or lower [Oatp1a4 (Oatp2)] in female than in male rat. DHEA treatment over 3 days (100 mg d−1) led to a further increase in Mrp3 expression only in female rats. Mrp2 expression was not influenced by DHEA treatment. Oatp1a1 and Oatp1b2 were significantly down‐regulated after DHEA treatment in both male and female rats. In contrast, Oatp1a4 was down‐regulated in male rats only.Conclusions  In rat, liver transport proteins of the Oatp and Mrp family are expressed and regulated in a gender‐specific manner according to sexual differences in the hepatic metabolism of steroids and drugs. These findings may partly explain the well‐known sex differences in hepatic handling of organic anions.
Alcohol and arterial wave reflections in middle aged and elderly men
Authors: Van Trijp M. J. C. A. , Bos W. J. W. , Van Der Schouw Y. T. , Muller M. , Grobbee D. E. , Bots M. L. 
Published: September 2005

AbstractBackground  Augmentation index (AIx) is a measure of arterial wave reflection, providing information on the workload of the heart. and is a possible marker for cardiovascular disease risk. The relation of alcohol consumption with cardiovascular disease (CVD) risk is U‐shaped with a protective effect of moderate alcohol consumption. The relation of alcohol consumption level with AIx has not been widely investigated, which prompted this study of the relation of alcohol consumption with AIx in a population‐based cohort of men aged 40–80 years.Methods  Three hundred and seventy‐four men (mean age 60·5 years) participated in this cross‐sectional study. Alcohol consumption and smoking habits were determined through a validated questionnaire. Fasting blood samples were drawn and analyzed for glucose and lipid levels and AIx was estimated by radial applanation tonometry using the SphygmoCor Device. The resultant data were analyzed using linear regression models.Results  Age, height, heart rate, blood pressure, packyears, current smoking, presence of CVD and hypertension were independently related to AIx. The relation of alcohol consumption with AIx was U‐shaped, with a significantly lower AIx in the group drinking 4–8 glasses/week (difference = −2·91%, 95% CI [−5·65; −0·18]) relative to those drinking 0–3 glasses/week. Additional adjustment for current smoking did not change this relationship, but adjustment for pulse wave velocity attenuated the relation.Conclusions  In a population‐based cohort of men aged 40–80 years the relation of alcohol consumption level with AIx was U‐shaped, further expanding the evidence for vascular protective effects of moderate alcohol intake.
Determination of a reference value for NG, NG‐dimethyl‐L‐arginine in 500 subjects
Authors: Schulze F. , Maas R. , Freese R. , Schwedhelm E. , Silberhorn E. , Böger R. H. 
Published: September 2005

AbstractBackground  Asymmetric dimethylarginine (ADMA) acts as an endogenous inhibitor of NO‐synthase. In the last years ADMA has emerged as a cardiovascular risk factor. The aim of this study was to determine a reference value for ADMA.Methods  Plasma samples of 500 healthy subjects in the 19–75 year age group were analyzed. Exclusion criteria from this study were smoking, any known significant disease, body‐mass‐index (BMI) above 30 kg m−2, elevated plasma lipid levels, impaired renal function, hypertension, and intake of any medication. The ADMA levels were determined by ELISA, (DLD Diagnostics, Hamburg, Germany).Results  Mean ADMA plasma concentration of the total population was 0·69 µmol L−1 (SD 0·20) and 95% of the measured values were in the range from 0·36 µmol L−1 to 1·17 µmol L−1. Women below 50 years of age had lower ADMA levels than men below 50 years of age [0·62 (0·17) µmol L−1 vs. 0·69 (0·19) µmol L−1; P = 0·001] and woman above 50 years of age had higher ADMA levels than men above 50 years of age [0·80 (0·22) µmol L−1 vs. 0·73 (0·20) µmol L−1; P = 0·036]. A regression analysis of ADMA levels and age was performed for each sex. The regression factor was r = 0·444 for women in a squared regression model (P < 0·001) and r = 0·212 for men in a linear regression model (P < 0·001).Conclusion  The study was able to define a reference value for ADMA plasma levels with 0·36–1·17 µmol L−1 and found sex dependent correlations between ADMA and age. Women showed a significant increase in ADMA plasma levels with onset of menopause.
Apolipoprotein B: a clinically important apolipoprotein which assembles atherogenic lipoproteins and promotes the development of atherosclerosis
Authors: OLOFSSON S.‐O. , BORÈN J. 
Published: September 2005

Abstract.Apolipoprotein (apo) B exists in two forms apoB100 and apoB48. ApoB100 is present on very low‐density lipoproteins (VLDL), intermediate density lipoproteins (IDL) and LDL. ApoB100 assembles VLDL particles in the liver. This process starts by the formation of a pre‐VLDL, which is retained in the cell unless converted to the triglyceride‐poor VLDL2. VLDL2 is secreted or converted to VLDL1 by a bulk lipidation in the Golgi apparatus. ApoB100 has a central role in the development of atherosclerosis. Two proteoglycan‐binding sequences in apoB100 have been identified, which are important for retaining the lipoprotein in the intima of the artery. Retention is essential for the development of the atherosclerotic lesion.
NblC, a novel component required for pigment degradation during starvation in Synechococcus PCC 7942
Authors: Sendersky Eleonora , Lahmi Roxane , Shaltiel Judith , Perelman Alexander , Schwarz Rakefet 
Published: September 2005

SummaryAdjustment of photosynthetic light harvesting to ambient conditions is essential to allow efficient energy capturing and to prevent surplus excitation and the cellular damage resulting from it. Degradation of the cyanobacterial light harvesting complex, the phycobilisome, is a general acclimation response occurring under various stress conditions. This study identifies a novel component, NblC, which mediates phycobilisome degradation under nitrogen, sulphur and phosphorus starvation. Our study indicates the requirement of NblC for efficient expression of nblA, an essential component of the degradation pathway; accumulation of nblA transcripts upon nutrient starvation was impaired in the NblC‐mutant. Furthermore, expression of NblC under the control of a foreign promoter resulted in accumulation of nblA transcripts and degradation of the light harvesting complex. Transcription of nblC is induced upon nutrient starvation, suggesting the requirement of elevated levels of NblC under these conditions. Importantly, NblC could not exert its positive effect on nblA expression in the absence of the response regulator NblR. Sequence alignment suggests kinase motifs as well as homology of NblC to anti‐sigma factors. Accordingly, we suggest a mode of action for this newly identified modulator, which provides new insights into regulation of gene expression in response to environmental stimuli.
Ng‐MIP, a surface‐exposed lipoprotein of Neisseria gonorrhoeae, has a peptidyl‐prolyl cis/trans isomerase (PPIase) activity and is involved in persistence in macrophages
Authors: Leuzzi Rosanna , Serino Laura , Scarselli Maria , Savino Silvana , Fontana Maria Rita , Monaci Elisabetta , Taddei Annarita , Fischer Gunter , Rappuoli Rino , Pizza Mariagrazia 
Published: September 2005

SummaryMacrophage infectivity potentiators (MIPs) are a family of surface‐exposed virulence factors of intracellular microorganisms such as Legionella, Chlamydia and Trypanosoma. These proteins display peptidyl‐prolyl cis/trans isomerase (PPIase) activity that is inhibited by immunosuppressants FK506 and rapamycin. Here we describe the identification and characterization in Neisseria gonorrhoeae of Ng‐MIP, a surface‐exposed lipoprotein with high homology to MIPs. The protein is an homodimer with rapamycin‐inhibited PPIase activity confirming that it is a functional member of the MIP family. A knock‐out strain, generated by deletion of the mip gene in N. gonorrhoeae F62 strain, was evaluated for its role in infection of mouse and human macrophages. We show that Ng‐MIP promotes the intracellular survival of N. gonorrhoeae in macrophages, highlighting a possible role of this protein in promoting the persistence of gonococcal infection.
Serine proteases from two cell types target different components of a complex that governs regulated intramembrane proteolysis of pro‐σK during Bacillus subtilis development
Authors: Zhou Ruanbao , Kroos Lee 
Published: September 2005

SummaryUpon starvation Bacillus subtilis undergoes a developmental process involving creation of two cell types, the mother cell and forespore. A signal in the form of a serine protease, SpoIVB, is secreted from the forespore and leads to regulated intramembrane proteolysis (RIP) of pro‐σK, releasing active σK into the mother cell. RIP of pro‐σK is carried out by a membrane‐embedded metalloprotease, SpoIVFB, which is inactive when bound by BofA and SpoIVFA. We have investigated the mechanism by which this complex is activated. By expressing components of the signalling pathway in Escherichia coli, we reconstructed complete inhibition of pro‐σK RIP by BofA and SpoIVFA, and found that SpoIVB serine protease activity could partially restore RIP, apparently by targeting SpoIVFA. Pulse‐chase experiments demonstrated that SpoIVFA synthesized early during B. subtilis sporulation is lost in a SpoIVB‐dependent fashion, coincident with the onset of pro‐σK RIP, supporting the idea that SpoIVB targets SpoIVFA to trigger RIP of pro‐σK. Loss of BofA depended not only on SpoIVB, but also on CtpB, a serine protease secreted from the mother cell. CtpB appeared to cleave BofA near its C‐terminus upon coexpression in E. coli, and purified CtpB degraded BofA. We propose that RIP of pro‐σK involves a three‐step proteolytic cascade in which SpoIVB first cleaves SpoIVFA, CtpB then cleaves BofA and finally SpoIVFB cleaves pro‐σK.
The liver stage of Plasmodium berghei inhibits host cell apoptosis
Authors: van de Sand Claudia , Horstmann Sebastian , Schmidt Anja , Sturm Angelika , Bolte Stefanie , Krueger Andreas , Lütgehetmann Marc , Pollok Jörg‐Matthias , Libert Claude , Heussler Volker T. 
Published: September 2005

SummaryPlasmodium berghei is the causative agent of rodent malaria and is widely used as a model system to study the liver stage of Plasmodium parasites. The entry of P. berghei sporozoites into hepatocytes has extensively been studied, but little is known about parasite–host interaction during later developmental stages of the intracellular parasite. Growth of the parasite far beyond the normal size of the host cell is an important stress factor for the infected cell. Cell stress is known to trigger programmed cell death (apoptosis) and we examined several apoptotic markers in P. berghei‐infected cells and compared their level of expression and their distribution to that of non‐infected cells. As none of the apoptotic markers investigated were found altered in infected cells, we hypothesized that parasite infection might confer resistance to apoptosis of the host cell. Treatment with peroxide or serum deprivation induced apoptosis in non‐infected HepG2 cells, whereas P. berghei‐infected cells appeared protected, indicating that the parasite interferes indeed with the apoptotic machinery of the host cell. To prove the physiological relevance of these results, mice were infected with high numbers of P. berghei sporozoites and treated with tumour necrosis factor (TNF)‐α/d‐galactosamine to induce massive liver apoptosis. Liver sections of these mice, stained for degraded DNA, confirmed that infected cells containing viable parasites were protected from programmed cell death. However, in non‐treated control mice as well as in TNF‐α‐treated mice a small proportion of dead intracellular parasites with degraded DNA were detected. Most hepatocytes containing dead parasites provoked an infiltration of immunocompetent cells, indicating that these cells are no longer protected from cell death.