bluuebunny/crossref_metadata_2025_split huggingface dataset:
High‐resolution structures of formate dehydrogenase from Candida boidinii
Authors: Schirwitz Katja , Schmidt Andrea , Lamzin Victor S. 
Published: May 2007

AbstractThe understanding of the mechanism of enzymatic recovery of NADH is of biological and of considerable biotechnological interest, since the essential, but expensive, cofactor NADH is exhausted in asymmetric hydrogenation processes, but can be recovered by NAD+‐dependent formate dehydrogenase (FDH). Most accepted for this purpose is the FDH from the yeast Candida boidinii (CbFDH), which, having relatively low thermostability and specific activity, has been targeted by enzyme engineering for several years. Optimization by mutagenesis studies was performed based on physiological studies and structure modeling. However, X‐ray structural information has been required in order to clarify the enzymatic mechanism and to enhance the effectiveness and operational stability of enzymatic cofactor regenerators in biocatalytic enantiomer synthesis as well as to explain the observed biochemical differences between yeast and bacterial FDH. We designed two single‐point mutants in CbFDH using an adapted surface engineering approach, and this allowed crystals suitable for high‐resolution X‐ray structural studies to be obtained. The mutations improved the crystallizability of the protein and also the catalytic properties and the stability of the enzyme. With these crystal structures, we explain the observed differences from both sources, and form the basis for further rational mutagenesis studies.
E‐dermatology: Emails about dermatological diseases on the Internet
Authors: ARICAN Ozer 
Published: May 2007

ABSTRACTToday, it is very easy to access information for both doctors and patients thanks to the Internet. The number of websites including health information is increasing day by day. This study was targeted to retrospectively investigate the dermatological questions received by the free consultation page of the health site for IsNet customers. The patients were assessed on the aspects of age and sex. The diseases were classified by the subject of the questions emailed and on what the patient would like to learn. It was also assessed whether the patient had seen a doctor before sending the email. The responses of the dermatologist were also classified as information on the disease and the treatment. A total of 607 questions were examined. One hundred and thirteen male and 69 female patients disclosed their sexes. Also, only 208 patients stated their age and the mean age was 29.3 years. Four hundred and sixty questions were related to the emailer. The questions usually asked were about treatment and requests for comprehensive information about the disease. The diseases most frequently asked about were: acne, hair diseases, pruritus, eczema, seborrheic dermatitis, psoriasis, superficial mycoses and vitiligo. Most responses were related to general information on diagnosis and treatment options. The Internet is frequently preferred for its speed; therefore, users do not give detailed information because it is not required. These results show there are differences in the intentions of our Internet users and the aims of our health website. In order to conduct these kinds of services more efficiently, preparing special forms would be useful. These data can be beneficial in the development of e‐medicine programs.
Organ‐dependent susceptibility of p53 knockout mice to 2‐amino‐3‐methylimidazo[4,5‐f]quinoline (IQ)
Authors: Hirata Akihiro , Tsukamoto Tetsuya , Yamamoto Masami , Takasu Shinji , Sakai Hiroki , Ban Hisayo , Yanai Tokuma , Masegi Toshiaki , Donehower Lawrence A. , Tatematsu Masae 
Published: May 2007

p53 knockout mice are now being frequently used to identify the carcinogenic potential of chemicals, thus it is important to precisely assess the susceptibility of the animals to various test chemicals. In the present study the susceptibility of p53 nullizygous(–/–), heterozygous(+/–), and wild‐type(+/+) mice to 2‐amino‐3‐methylimidazo[4,5‐f]quinoline (IQ) was investigated. Mice of all three genotypes were first fed a diet containing 100 or 300 p.p.m. IQ for 15 weeks in a short‐term experiment. p53(+/–) and (+/+) mice were then treated with IQ for 40 weeks and maintained without further treatment for an additional 12 weeks in the long‐term experiment. In the forestomach, the incidence of squamous cell hyperplasia was significantly higher in p53(–/–) than in (+/–) and (+/+) mice at 15 weeks and higher in (+/–) mice than (+/+) mice with long‐term IQ treatment, indicating an elevated susceptibility of p53 knockout mice. In contrast, in the liver, various hepatocellular lesions developed mainly in female mice with long‐term IQ exposure but no significant differences were evident between p53 knockout and wild‐type mice, indicating a lack of elevated susceptibility in the knockout animals. Furthermore, polymerase chain reaction‐single strand conformation polymorphism and sequencing analysis revealed relatively high (13/30) and low (1/15) incidences of p53 mutations (exons 5–8) in squamous cell hyperplasia and hepatocellular tumors, respectively. These results clearly indicate that the susceptibility of p53 knockout mice is organ‐dependent, coinciding to some extent with the likelihood of p53 gene alteration in the induced tumors. (Cancer Sci 2007; 98: 1164–1173)
Neurological, cardiovascular and metabolic effects of mefloquine in healthy volunteers: a double‐blind, placebo‐controlled trial
Authors: DAVIS TIMOTHY M. E. , DEMBO LAWRENCE G. , KAYE‐EDDIE SALLY A. , HEWITT BENJAMIN J. , HISLOP ROBERT G. , BATTY KEVIN T. 
Published: May 2007

1To assess neurological, cardiovascular, metabolic and other side‐effects of mefloquine given in conventional prophylactic dose to healthy volunteers, a double‐blind, randomized, placebo‐controlled trial was conducted. In addition, the identity of the active drug was concealed until the end of the trial. 2A total of 106 healthy adults were recruited, of whom 95 (mean age 24 years; 45% males) completed the full study protocol. 3Subjects had a baseline assessment, received placebo as first dose, were randomized to mefloquine 250 mg or placebo weekly for 4 weeks starting a week later, and were reassessed after the 2nd and 4th active/placebo doses. Subjects kept a daily symptom diary from 2 weeks before until 2 weeks after the dosing period. 4Plasma mefloquine assay suggested compliance in all 46 subjects allocated active treatment (week 5 mean±s.d.; 2.35±0.94 μmol l−1). Mefloquine did not alter calcium homoeostasis but produced a mean 0.5 mmol l−1 fall in serum glucose over the study period (P<0.001) and relative hyperinsulinaemia. Symbol digit modalities, and digit forwards and backwards test scores, were similar in active and placebo groups across the three assessments, as were lying/standing blood pressure and high‐tone hearing loss. Electrocardiographic QTc interval prolongation and diarrhoea were mild but transient side‐effects of mefloquine (P<0.01). Neurological symptoms were comparable in the two groups throughout the study. There was no evidence of drug toxicity in 11 subjects who withdrew. 5Mefloquine prophylaxis does not appear to produce low‐grade but debilitating neurological symptoms or to alter the results of sensitive tests of cerebral function. However, there may be situations in which mefloquine might contribute to hypoglycaemia and cardiac dysrhythmias.
The elimination of diazepam in Chinese subjects is dependent on the mephenytoin oxidation phenotype
Authors: WAN JIE , XIA HUI , HE NAN , LU YI‐QING , ZHOU HONG‐HAO 
Published: May 2007

1The disposition of diazepam and desmethyldiazepam was studied in 21 healthy male Chinese subjects who were phenotyped with mephenytoin. Four poor metabolizers (PM) were identified by phenotyping with mephenytoin and by genotyping for CYP2C19. 2Serum diazepam and desmethyldiazepam concentrations were measured by high performance liquid chromatography in samples drawn up to 24 days after administration. 3The plasma elimination half‐lives of diazepam (100.8±32.3 h) and desmethyldiazepam (219.9±62.7 h) in PMs were significantly longer than those (34.7±23.0 h for diazepam, 103.1±25.9 h for desmethyldiazepam) of the 17 phenotyped extensive metabolizers (EM), and those (30.8±24.9 h for diazepam, 103.1±27.5 h for desmethyldiazepam) of the five genotyped EMs. 4The mephenytoin S/R ratios were significantly correlated with the plasma half‐lives of diazepam (r=0.543, P<0.05) and desmethyldiazepam (r=0.522, P<0.05), and with the clearance (r=−0.524, P<0.05) of diazepam in 21 subjects. 5These results are compatible with the conclusion that both diazepam and desmethyldiazepam are metabolized by cytochrome P450 CYP2C19 in the Chinese population. 6The mephenytoin S/R ratios in nine EMs who drank alcohol frequently were significantly higher than those of seven EMs who were non‐drinkers, but the plasma kinetics of diazepam and desmethyldiazepam were not significantly different between the two groups. The explanation for these finding is not clear.
Double‐blind comparative study of the antidepressant, unwanted and cardiac effects of minaprine and amitriptyline
Authors: EDWARDS J. GUY , DINAN TIMOTHY G. , WALLER DEREK G. , GREENTREE STEPHEN G. 
Published: May 2007

1A double‐blind, multicentre study comparing the efficacy and safety of minaprine and amitriptyline in patients with major depression was carried out. Five hundred and thirty‐one patients were randomly assigned to treatment with either minaprine 100 mg, 200 mg or 300 mg day−1 or with amitriptyline 150 mg day−1 (75 mg during the first week). The medication was administered for 6 weeks. 3Efficacy was assessed using the Hamilton rating scale for depression (HDRS), the Montgomery‐Åsberg depression rating scale (MADRS) and visual analogue assessments of depression carried out by both the investigators and patients. Unwanted effects were assessed by a questionnaire and spontaneous reporting. In a subgroup of patients cardiovascular effects were investigated by high speed ECG and systolic time intervals. 3Patients in each treatment group showed a significant clinical improvement (P<0.01) from baseline. The mean HDRS and MADRS scores adjusted for baseline differences, showed significantly less improvement in the minaprine 100 mg once daily (P<0.01) and the minaprine 300 mg daily (P<0.01) groups than in the amitriptyline group at both week 4 and week 6. The MADRS score at week 4 suggested that 200 mg day−1 minaprine was less effective than amitriptyline (P<0.05), but there was no difference between the two groups at week 6 on either the HDRS or the MADRS. 4Both drugs were well tolerated and there were no significant differences between treatment groups in any of the safety and tolerance assessments. In the ECG, amitriptyline produced a significant increase in the heart rate and PR interval while minaprine had no effect on electrocardiographic measurements. Neither drug produced changes in the systolic time intervals.
Familial partial lipodystrophy due to the LMNA R482W mutation with multinodular goitre, extrapyramidal syndrome and primary hyperaldosteronism
Authors: Vantyghem M. C. , Faivre‐Defrance F. , Marcelli‐Tourvieille S. , Fermon C. , Evrard A. , Bourdelle‐Hego M. F. , Vigouroux C. , Defebvre L. , Delemer B. , Wemeau J. L. 
Published: May 2007

SummaryObjective  To describe new data about the wide phenotypic variability of diseases due to mutations in the lamin A/C gene (LMNA).Design  We report a complex phenotype in a patient with familial partial lipodystrophy of the Dunnigan type (FPLD) and study the frequency of her unusual clinical signs in 19 other LMNA‐mutated lipodystrophic patients from 8 different families and 14 non‐mutated family members.Case Report  The patient was diagnosed with FPLD due to the R482W LMNA mutation after familial screening. Surprisingly, she had no biological signs of insulin resistance. The presence of hypertension with hypokalaemia led to the diagnosis of primary hyperaldosteronism. Thyroid investigations showed a euthyroid multinodular goiter. In addition, the patient exhibited a juvenile akineto‐hypertonic syndrome.Results  Goiter was identified with a similar frequency (55%) in LMNA‐mutated lipodystrophic patients (11 out of 20, originating from 5 families among 8) compared to non‐mutated family controls (35%; 5 patients out of 14, all originating from the same family). No case of primary hyperaldosteronism or extrapyramidal syndrome was identified in other studied subjects, either LMNA‐mutated or not.Conclusions  This R482W‐LMNA mutated patient showed an association of features (primary hyperaldosteronism, euthyroid goiter and extra‐pyramidal syndrome, raising the question of a link with her laminopathy. Prevalence of goiter tended to be higher in LMNA‐mutated than in non‐mutated subjects. Hyperaldosteronism seems coincidental. Although extrapyramidal syndrome has never been reported in lipodystrophic patients, it may nevertheless be linked to the LMNA mutation since multiple neurological features have been associated with alterations in lamins A/C.
Utility of HBME‐1 immunostaining in serous effusions
Authors: ASCOLI V. , CARNOVALE‐SCALZO C. , TACCOGNA S. , NARDI F. 
Published: May 2007

Utility of HBME‐1 immunostaining in serous effusionsHBME‐1 is an anti‐mesothelial cell monoclonal antibody derived from human mesothelioma cells. We investigated 227 body cavity effusions to test its utility in differentiating mesothelioma from adenocarcinoma. HBME‐1 outlined cell membranes in non‐neoplastic mesothelial cells. Thick surface staining was observed on all mesotheliomas. HBME‐1 reactivity was also detected in 24% of metastatic carcinomatous effusions. Most ovarian carcinomas (83%) reacted with this antibody, showing surface staining. Cytoplasmic HBME‐1 immunoreactivity was observed in a small proportion of non‐ovarian adenocarcinomas (14%). Despite its limited specificity, HBME‐1 might be added to the battery of other markers of epithelial and/or mesothelial differentiation to be used in cases of suspected mesothelioma. Evaluation of suspicious cells should include careful study of the pattern of immunostaining.
Fine needle aspiration (FNA) biopsy of orbital masses: a critical review of 51 cases
Authors: ZEPPA P. , TRANFA F. , ERRICO M. E. , TRONCONE G. , FULCINITI F. , VETRANI A. , BONAVOLONTÀ G. , PALOMBINI L. 
Published: May 2007

Fine needle aspiration (FNA) biopsy of orbital masses: a critical review of 51 cases FNA biopsy of 51 orbital masses is critically reviewed. Aspiration was performed with a 23 G needle inserted by an ophthalmologist; the smears were prepared by a cytologist. Forty‐two cases (83%) were correctly diagnosed as benign or malignant either with (68%) or without (15%) correct specification of the histology. There were two false‐negative and seven inadequate cases. Immunocytochemical stains were performed in five cases using the following antibodies: L26 (Pan B), UCHL1 (Pan T), and immunoglobulin light chains (three cases) in order to distinguish inflammatory pseudotumours from low‐grade non‐Hodgkin's lymphomas. In two cases we used CAM 5.2 (a monoclonal cytokeratin cocktail) and vimentin to ascertain the epithelial origin of two metastatic tumours. In five other cases cytospins were not adequately cellular for immunocytochemistry. Insufficient material and one false‐negative sample were obtained from very fibrotic lesions or from posteriorly located lesions. The results are discussed and compared with other series reported in the literature. Orbital FNA biopsy may be considered a useful tool in the diagnostic approach to orbital masses in which the relatively high number of inadequate aspirations is offset by a low cost‐benefit ratio.
Diagnostic impression cytology: a simple technique for the diagnosis of external eye disease
Authors: DIVANI S. N. , MARGARI C. , ZIKOS G. A. , ZIKOS A. , PAPAVASSILIOU G. B. 
Published: May 2007

Diagnostic impression cytology: a simple technique for the diagnosis of external eye disease The technique of impression cytology was used for cytologic examination of conjunctival samples from 128 patients with a variety of external eye diseases. The method of sample collection and the staining procedure are described. Microscopic examination showed 62 cases with allergic conjunctivitis, 23 with bacterial or viral infection, 26 cases with changes typical of dry eye and 17 cases with non‐specific chronic inflammation. The cytologic features and numerous applications of impression cytology are discussed.
Cytologic evaluation of conjunctival epithelium using Cytobrush‐S: value of slide preparation by ThinPrep technique
Authors: KOBAYASHI T. K. , UEDA M. , NISHINO T. , ISHIDA Y. , TAKAMURA E. , TSUBOTA K. 
Published: May 2007

Cytologic evaluation of conjunctival epithelium using Cytobrush‐S: value of slide preparation by ThinPrep technique Recent clinical trials have indicated that an automated smear apparatus (ThinPrep process) of sample preparation has great diagnostic sensitivity. In this study, conjunctival brush cytology prepared using the ThinPrep method was applied in ocular surface disorders especially for dry eye status. To assess its diagnostic value in cellular samples, 17 patients with keratoconjunctivitis sicca (KCS) and 10 normal volunteer patients were examined using this technique. Conjunctival cells from normal controls revealed fine chromatin and polyhedral cytoplasm without having keratinized cytoplasm. On the other hand, the cellular samples from KCS revealed increased keratinized cells with pyknotic nuclei. They also contained extremely elongated cells. In KCS patients, the mean number of keratinized cells was significantly higher (34.1 cells/300 cells) than that of the normal control group (0.2 cells/300 cells). In patients with KCS, inflammatory cell counts were also higher than those of normal controls. Conjunctival cytology by means of the ThinPrep method obviously deserves additional trials as an adjunct in the cytology of dry eye states, especially in quantitative ocular evaluation for various ocular lesions.
Cytological aspects of uterine cervical adenocarcinoma, adenosquamous carcinoma and combined adenocarcinoma‐squamous carcinoma: appraisal of diagnostic criteria for in situ versus invasive lesions
Authors: HAYES M. M. M. , MATISIC J. P. , CHEN C.‐J. , MOHAMED A. , ANDERSON G. H. , LERICHE J. C. , AMY R. 
Published: May 2007

Cytological aspects of uterine cervical adenocarcinoma, adenosquamous carcinoma and combined adenocarcinoma‐squamous carcinoma: appraisal of diagnostic criteria for in situ versus invasive lesionsThis paper reports the cytological findings based on air‐dried smears in a retrospective series of 143 cases of endocervical adenocarcinoma, combined adenocarcinoma‐squamous carcinoma and adenosquamous carcinoma drawn from the files of the BC Cancer Registry. Cervical cytology smears were available before biopsy in 131 patients, but in 18 cases the cytology showed no abnormality. Malignant changes or high‐grade atypia of glandular and/or squamous cells (defined as moderate or severe dyskaryosis) were detected in 103 cases. In 46 cases, only a high‐grade squamous abnormality was detected. Low‐grade glandular and/or squamous lesions were detected in nine cases and one showed atypical endometrial‐type glands. The cervical smears of 64 cases were reviewed in detail to determine the important cytomorphological criteria of in situ and invasive adenocarcinoma in air‐dried smears, the technique used for preparing PAP smears in British Columbia. Endocervical cells were absent in four cases. Numerous (>10) groups of glandular cells were present in 51 cases. Important clues to the diagnosis of adenocarcinoma included crowding of nuclei, stratification of nuclei, loss of polarity, syncytial balls and papillary groups of glandular cells, nuclear enlargement, nuclear pleomorphism, and the presence of free‐lying atypical glandular cells. Nuclear hyperchromatism, chromatin pattern, nuclear borders, nuclear membranes, and numbers and morphology of nucleoli were not helpful criteria in our material. Criteria enabling reliable distinction between in situ and invasive adenocarcinoma and/or mixed adenocarcinoma‐squamous carcinoma could not be established.
Impact of nurse prescribing: a qualitative study
Authors: Bradley Eleanor , Nolan Peter 
Published: May 2007

Abstract Title. Impact of nurse prescribing: a qualitative study Aim.  This paper is a report of an investigation of the impact of prescribing on a group of recently qualified nurse prescribers in the United Kingdom.Background.  The creation of advanced nursing roles, and specific skills such as nurse prescribing, has resulted in nurses taking on roles that have traditionally been associated with doctors. The non‐doctor prescribing initiative is continually developing and many nurses are now able to prescribe independently from almost the same range of medicines as doctors. Despite the advantages that appear to stem from nurses prescribing, some nurse researchers have been cautious about the impact that prescribing may have on the nursing profession.Method.  Interviews were conducted during 2005 and 2006 with 45 nurse prescribers. All nurses had successfully qualified and registered as prescribers. Interviews were analysed thematically in line with the principles of grounded theory.Findings.  Prescribing allows nurses to overcome difficulties in the healthcare system that previously delayed patients’ access to medicines. Prescribing is viewed as more than an ‘add on’ to current roles, it complements many aspects of nursing and integrates previously diffuse aspects of the nursing role. This enables nurses to adopt a more holistic approach to patient care and prescribing. Prescribing has the potential to increase job satisfaction and autonomous working, with the result that nurses are more likely to involve patients in decision‐making about their care.Conclusions.  Prescribing enhances nurses’ knowledge about medication and increases their confidence to engage in prescribing decisions across the healthcare team. Nurse prescribing has the potential to improve service‐user care, enhance collaboration and widen discussions about medicines. However, team members need to be prepared for the impact nurse prescribing could have on the dynamics of the multidisciplinary team. Preparatory information about nurse prescribing should be provided to all team members by trainee nurse prescribers. Information could include details about the proposed scope of future prescribing roles, allowing team members to consider how their roles could develop.