Tissue-specific expression of a human Polymorphic Epithelial mucin (MUCI) in transgenic mice

The human MUC1 gene codes for the core protein of a mucin which is expressed by glandular epithelia and the carcinomas which develop from these tissues. The core protein is aberrantly glycosylated in cancers, and some antibodies show specificity in their reactions with the cancer-associated mucin, which also contains epitopes recognized by T-cells from breast and pancreatic cancer patients. For evaluating the potential use of mucin-reactive antibodies and mucin-based immunogens in cancer patients, a mouse model, expressing the MUC1 gene product PEM (polymorphic epithelial mucin) as a self antigen, would be extremely useful. To this end, we have developed transgenic mouse strains expressing the human MUC1 gene product in a tissue-specific manner. The TG4 mouse strain was established using a 40-kilobase fragment containing 4.5 kilobases of 5\u27 and 27 kilobases of 3\u27 flanking sequence. The TG18 strain was developed using a 10.6-kilobase SacII fragment from the 40-kilobase fragment; this fragment contained 1.6 kilobases of 5\u27 sequence and 1.9 kilobases of 3\u27 flanking sequence. Both strains showed tissue specificity of expression of the MUC1 gene, which was very similar to the profile of expression seen in human tissues. The antibody SM-3 is directed to a core protein epitope, which is selectively exposed in breast cancers and which shows a more restricted distribution on normal human tissues. It was established that the distribution of the SM-3 epitope of PEM in the tissues of the transgenic mice is similar to that seen in humans. The transgenic mouse strains described here should form the basis for the development of a preclinical model for the evaluation of PEM-based antigens and of antibodies directed to PEM in cancer therapy

Suggested reference ranges in clinical chemistry for apparently healthy males and females of Pakistan.

Abstract Seven hundred and eighty six apparently healthy males (418) and females (368) aged 0-69 years were randomly selected for estimation of reference ranges of 24 serum analytes at the clinical chemistry laboratory of The Ago Khon University Hospital (AKUH). Of the total study samples, 56% (439/786) were in the poediatric age group (0-14 years) and 44% (347/786) in the adult (1 5_60 years) group. Beckman Astra Ideal Autoanalyzer was used for all the estimations. Moon and standard deviations (SD) were calculated for each of the age groups. Reference ranges were calculated following standard methods of the International Federation of Clinical Chemistry (IFCC) and International Committee far Standardization in Haematology (ICSH) (JPMA 43:113, 1993)

Trefoil factor 2 (Tff2) deficiency in murine digestive tract influences the immune system

Background & Aims: The gastrointestinal trefoil factor family (TFF1, TFF2, TFF3) peptides are considered to play an important role in maintaining the integrity of the mucosa. The physiological role of TFF2 in the protection of the GI tract was investigated in TFF2 deficiency. Methods: TFF2-/- mice were generated and differential expression of various genes was assessed by using a mouse expression microarray, quantitative real time PCR, Northern blots or immunohistochemistry. Results: On an mRNA level we found 128 differentially expressed genes. We observed modulation of a number of crucial genes involved in innate and adaptive immunity in the TFF2-/- mice. Expression of proteasomal subunits genes (LMP2, LMP7 and PSMB5) involved in the MHC class I presentation pathway were modulated indicating the formation of immunoproteasomes improving antigen presentation. Expression of one subunit of a transporter (TAP1) responsible for importing degraded antigens into ER was increased, similarly to the BAG2 gene that modulates chaperone activity in ER helping proper loading on MHC class I molecules. Several mouse defensin (cryptdin) genes coding important intestinal microbicidal proteins were up-regulated as a consequence of TFF2 deficiency. Normally moderate expression of TFF3 was highly increased in stomach

Building motivation to participate in a quality improvement collaborative in NHS hospital trusts in Southeast England: a qualitative participatory evaluation.

OBJECTIVES: This study explores the barriers and facilitators that impact on the motivation of practitioners to participate in a quality improvement collaborative. DESIGN: A qualitative and formative evaluation using a participatory approach, the researcher-in-residence model which embraces the concept of 'coproducing' knowledge between researchers and practitioners using a range of research methods such as participant observation, interviews and documentary analysis. The design, creation and application of newly generated evidence are facilitated by the researcher through negotiation and compromise with team members. PARTICIPANTS: Senior and middle managers, doctors and nurses. SETTING: Two hospitals in Southeast England participating in a Patient Safety Improvement Collaborative and the facilitator (host) of the collaborative, based in Central London. RESULTS: The evaluation has revealed facilitators and barriers to motivation categorised under two main themes: (1) inherent motivation and (2) factors that influence motivation, interorganisational and intraorganisational features as well as external factors. Facilitators included collaborative 'champions,' individuals who drove the quality improvement agenda at a local level, raising awareness and inspiring colleagues. The collaborative itself acted as a facilitator, promoting shared learning as well as building motivation for participation. A key barrier was the lack of board engagement in the participating National Health Service organisations which may have affected motivation among front-line staff. CONCLUSIONS: Collaboratives maybe an important way of engaging practitioners in quality improvement initiatives. This study highlights that despite a challenging healthcare environment in the UK, there remains motivation among individuals to participate in quality improvement programmes as they recognise that improvement approaches may facilitate positive change in local clinical processes and systems. Collaboratives can harness this individual motivation to facilitate spread and adoption of improvement methodology and build engagement across their membership

Building motivation to participate in a quality improvement collaborative in NHS hospital trusts in Southeast England: a qualitative participatory evaluation.

OBJECTIVES: This study explores the barriers and facilitators that impact on the motivation of practitioners to participate in a quality improvement collaborative. DESIGN: A qualitative and formative evaluation using a participatory approach, the researcher-in-residence model which embraces the concept of 'coproducing' knowledge between researchers and practitioners using a range of research methods such as participant observation, interviews and documentary analysis. The design, creation and application of newly generated evidence are facilitated by the researcher through negotiation and compromise with team members. PARTICIPANTS: Senior and middle managers, doctors and nurses. SETTING: Two hospitals in Southeast England participating in a Patient Safety Improvement Collaborative and the facilitator (host) of the collaborative, based in Central London. RESULTS: The evaluation has revealed facilitators and barriers to motivation categorised under two main themes: (1) inherent motivation and (2) factors that influence motivation, interorganisational and intraorganisational features as well as external factors. Facilitators included collaborative 'champions,' individuals who drove the quality improvement agenda at a local level, raising awareness and inspiring colleagues. The collaborative itself acted as a facilitator, promoting shared learning as well as building motivation for participation. A key barrier was the lack of board engagement in the participating National Health Service organisations which may have affected motivation among front-line staff. CONCLUSIONS: Collaboratives maybe an important way of engaging practitioners in quality improvement initiatives. This study highlights that despite a challenging healthcare environment in the UK, there remains motivation among individuals to participate in quality improvement programmes as they recognise that improvement approaches may facilitate positive change in local clinical processes and systems. Collaboratives can harness this individual motivation to facilitate spread and adoption of improvement methodology and build engagement across their membership

Observation of second-harmonic generation induced by pure spin currents

Extensive efforts are currently being devoted to developing a new electronic technology, called spintronics, where the spin of electrons is explored to carry information. [1,2] Several techniques have been developed to generate pure spin currents in many materials and structures. [3-10] However, there is still no method available that can be used to directly detect pure spin currents, which carry no net charge current and no net magnetization. Currently, studies of pure spin currents rely on measuring the induced spin accumulation with optical techniques [5, 11-13] or spin-valve configurations. [14-17] However, the spin accumulation does not directly reflect the spatial distribution or temporal dynamics of the pure spin current, and therefore cannot monitor the pure spin current in a real-time and real-space fashion. This imposes severe constraints on research in this field. Here we demonstrate a second-order nonlinear optical effect of the pure spin current. We show that such a nonlinear optical effect, which has never been explored before, can be used for the non-invasive, non-destructive, and real-time imaging of pure spin currents. Since this detection scheme does not rely on optical resonances, it can be generally applied in a wide range of materials with different electronic bandstructures. Furthermore, the control of nonlinear optical properties of materials with pure spin currents may have potential applications in photonics integrated with spintronics.Comment: 19 pages, 3 figures, supplementary discussion adde

Coarctation of the aorta and mild to moderate developmental delay in a child with a de novo deletion of chromosome 15(q21.1q22.2)

BACKGROUND: Deletion of 15q21q22 is a rare chromosomal anomaly. To date, there have been nine reports describing ten individuals with different segmental losses involving 15q21 and 15q22. Many of these individuals have common features of growth retardation, hypotonia and moderate to severe mental retardation. Congenital heart disease has been described in three individuals with interstitial deletion involving this region of chromosome 15. CASE PRESENTATION: We report a child with coarctation of the aorta, partial agenesis of corpus callosum and mild to moderate developmental delay, with a de novo deletion of 15q21.1q22.2, detected by the array Comparative Genomic Hybridization (CGH). We utilized chromosome 15-specific microarray-based CGH to define the chromosomal breakpoints in this patient. CONCLUSION: This is the first description of mapping of an interstitial deletion involving the chromosome 15q21q22 segment using the chromosome 15-specific array-CGH. The report also expands the spectrum of clinical phenotype associated with 15q21q22 deletion

What is the effect of riskshaw noise on its driver?

Objective: Occupational hearing loss is common in the industrialized world. Road noise is a major contributor to perceived environmental noise. The objective of this study was to assess hearing loss in rickshaw drivers due to rickshaw noise.Methods: Hearing loss in rickshaw drivers and taxi drivers of Karachi who were 50 years of age or younger was estimated, with a Smith Hearing Screening (SHS) questionnaire that was modified, translated into the national language, Urdu and field tested prior to administration.Results: Interviews for 91 rickshaw drivers and 94 taxi drivers were completed. All subjects were male; mean ages were 34 and 33 years for rickshaw and taxi drivers respectively. None of the rickshaws were fitted with silencers. Rickshaw drivers were about thrice as likely to be screened as hearing impaired by the SHS questionnaire (RR 2.9, 95% confidence interval 1.6, 5.0), twice as likely to report tinnitus (RR 2.2, 95% confidence interval, 1.1, 3.3) and two and a half times as likely to have difficulty in following telephonic conversations (RR 2.4, 95% confidence interval 1.2, 4.8).CONCLUSION: There is loss of hearing and tinnitus among rickshaw drivers that could be attributed to their trade. Use of silencers by rickshaw drivers could result in less hearing loss among rickshaw drivers and less noise in the environment for the other 11 million residents in the city

SNP genotyping to screen for a common deletion in CHARGE Syndrome

BACKGROUND: CHARGE syndrome is a complex of birth defects including coloboma, choanal atresia, ear malformations and deafness, cardiac defects, and growth delay. We have previously hypothesized that CHARGE syndrome could be caused by unidentified genomic microdeletion, but no such deletion was detected using short tandem repeat (STR) markers spaced an average of 5 cM apart. Recently, microdeletion at 8q12 locus was reported in two patients with CHARGE, although point mutation in CHD7 on chromosome 8 was the underlying etiology in most of the affected patients. METHODS: We have extended our previous study by employing a much higher density of SNP markers (3258) with an average spacing of approximately 800 kb. These SNP markers are diallelic and, therefore, have much different properties for detection of deletions than STRs. RESULTS: A global error rate estimate was produced based on Mendelian inconsistency. One marker, rs431722 exceeded the expected frequency of inconsistencies, but no deletion could be demonstrated after retesting the 4 inconsistent pedigrees with local flanking markers or by FISH with the corresponding BAC clone. Expected deletion detection (EDD) was used to assess the coverage of specific intervals over the genome by deriving the probability of detecting a common loss of heterozygosity event over each genomic interval. This analysis estimated the fraction of unobserved deletions, taking into account the allele frequencies at the SNPs, the known marker spacing and sample size. CONCLUSIONS: The results of our genotyping indicate that more than 35% of the genome is included in regions with very low probability of a deletion of at least 2 Mb