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PubMed1991

Identification of deletion mutations and three new genes at the familial polyposis locus.

Small (100-260 kb), nested deletions were characterized in DNA from two unrelated patients with familial adenomatous polyposis coli (APC). Three candidate genes located within the deleted region were ascertained and a previous candidate gene, MCC, was shown to be located outside the deleted region. One of the new genes contained sequence identical to SRP19, the gene coding for the 19 kd component of the ribosomal signal recognition particle. The second, provisionally designated DP1 (deleted in polyposis 1), was found to be transcribed in the same orientation as MCC. Two other cDNAs, DP2 and DP3, were found to overlap, forming a single gene, DP2.5, that is transcribed in the same orientation as SRP19.

Adenomatous Polyposis Coli↗

PubMed1994

Organization and sequence of the HpaII restriction-modification system and adjacent genes.

We report the organization of the HpaII restriction and modification (R-M) system from Haemophilus parainfluenzae (recognition sequence: 5'...CCGG...3'), the sequence of the gene coding for the HpaII restriction endonuclease, and the sequence of the upstream flanking DNA. The HpaII system comprises two genes, hpaIIM, coding for the methyltransferase (MTase; 358 amino acids (aa), 40.4 kDa: product, Cm5CGG), and hpaIIR, coding for the restriction endonuclease (ENase; 358 aa, 40.9 kDa: product, C'CGG). The genes are adjacent, they have the same orientation, and they occur in the order hpaIIM then hpaIIR. The ENase bears little as sequence similarity to the isoschizomeric R.BsuFI and R.MspI ENases. Upstream of, and partly overlapping hpaIIM is the coding sequence for a 141-aa protein that resembles the very-short-patch-repair endonuclease (Vsr) of Escherichia coli. Upstream of that is the coding sequence for a protein that resembles valyl-tRNA synthetase (ValS).

Amino Acid Sequence↗

PubMed2006

Impact and implications of disruptive behavior in the perioperative arena.

BACKGROUND: There is a growing concern about the role of human factor issues and their effect on patient safety and clinical outcomes of care. Problems with disruptive behaviors negatively affect communication flow and team dynamics, which can lead to adverse events and poor quality outcomes. STUDY DESIGN: A 25-question survey tool was used to assess the status and significance of disruptive behaviors around perioperative services in a large metropolitan academic medical center. Results were analyzed and compared with those from a national databank to identify areas of concern and opportunities for improvement. RESULTS: Disruptive behaviors were a common occurrence in the perioperative setting. These types of behaviors were most prevalent in attending surgeons. Disruptive behaviors increased levels of stress and frustration, which impaired concentration, impeded communication flow, and adversely affected staff relationships and team collaboration. These events were perceived to increase the likelihood of medical errors and adverse events and to compromise patient safety and quality of care. CONCLUSIONS: Disruptive behaviors in the perioperative arena have a significant impact on team dynamics and communication flow, which can have a negative impact on patient care. Organizations need to recognize the prevalence and significance of disruptive behaviors and develop policies and processes to address the issue. Key areas of focus include recognition and awareness, organizational and cultural commitment, implementation of appropriate codes of behavior policies and procedures, and provision of education and training programs to discuss contributing factors and tools to build effective communication and team collaboration skills.

Academic Medical Centers↗

PubMed2002

Universal inheritable barcodes for identifying organisms.

The needs for recognition of novel conventional or transgenic organisms include protection of patented or Identity Preserved lines, detecting transgenics and tracing dispersal. We propose simple 'Biobarcodes' using universal PCR primers to recognize the universal 'nonsense' recognition site of all biobarcodes, followed by a variable nonsense sequence. The proposed sequences are long enough to allow recognition in spite of mutations, have stop codons to prevent coding, and will not self anneal. Sequences of PCR-amplified biobarcodes can be compared to a universal database.

DNA, Plant↗

PubMedDate not supplied

An N-terminal peptide from p60src can direct myristylation and plasma membrane localization when fused to heterologous proteins.

The src gene product, p60src, of Rous sarcoma virus (RSV) is a tyrosine-specific protein kinase which is associated with the plasma membrane of infected cells. Myristic acid is bound in an amide linkage to glycine 2 of p60src. Of the N-terminal 30 kilodaltons of p60src, only amino acids 1-14 are required for myristylation, and myristylation of p60src may be required for its membrane association, and for cell transformation. To test the hypothesis that the first 14 amino acids of p60src contain a recognition sequence for myristylation, we have fused the DNA sequence coding for these amino acids to either the fps gene of the F36 derivative of Fujinami sarcoma virus (FSV), or to the chimpanzee alpha-globin gene. We report here that although the fusion proteins were myristylated, the parental proteins were not, and unlike the non-myristylated F36 p91fps which was not bound to the plasma membrane, the myristylated fusion protein was bound, like p60src. We conclude that the first 14 amino acids of p60src contain a sequence which is sufficient for myristylation, and which may direct proteins to the plasma membrane.

Amino Acid Sequence↗

PubMed1996

Identification of TRP-2 as a human tumor antigen recognized by cytotoxic T lymphocytes.

The infusion of TIL586 along with interleukin-2 into the autologous patient with metastatic melanoma resulted in the objective regression of tumor. A gene encoding a tumor antigen recognized by TIL586 was previously isolated and shown to encode gp75 or TRP-1. Here we report that TRP-2 was identified as a second tumor antigen recognized by a HLA-A31-restricted CTL clone derived from the TIL586 cell line. The peptide LLPGGRPYR epitope was subsequently identified from the coding region of TRP-2 based on studies of the recognition of truncated TRP-2 cDNAs and the HLA-A31 binding motif. This epitope peptide was capable of sensitizing target cells for lysis by a CTL clone at 1 nM peptide concentration. Although some modified peptides could be recognized by the CTL clone, none were found to be better recognized by T cells than the parental peptide. Like other melamona differentiation antigens, TRP-2 was only expressed in melanoma, melanocytes, and retina, but not in other human tissues tested.

Amino Acid Sequence↗

PubMed1996

Structure and expression of a murine homologue of sky receptor tyrosine kinase gene.

To identify new receptor tyrosine kinases (RTKs), we screened cDNAs from mouse mammary tumor cells and mouse brain. A homology search of the complete cDNA sequences obtained showed that one cDNA was a murine homologue of recently reported human sky [Ohashi, K. et al. (1994) Oncogene 9, 699-705]. Another cDNA obtained was also related to sky but had a 5' upstream sequence similar to brt [Fujimoto, J. and Yamamoto, T. (1994) Oncogene 9, 693-698]. Analysis of the 5' region of the sky genomic DNA revealed that brt-type and sky-type sequences are encoded by the sky gene in different exons. The upstream region of the sky-type coding exon is highly GC-rich and contains potential recognition sites for the Sp1 trans-acting factor, but lacks TATA and CAAT boxes, features commonly found in promoters of other RTKs. To examine whether this upstream region functions as a promoter, we fused it with chloramphenicol acetyltransferase (CAT) gene and transfected the construct into COS-7 cells. The results of the CAT assay showed that the sky upstream region retains a significant promoter activity. Furthermore, primer extension analysis revealed that the transcription starts at -240 nt upstream from the sky translation initiation codon. These observations suggest that the brt- and sky-types of mRNA are transcribed from a single sky gene by an alternative promoter usage.

Animals↗

PubMed2004

On the sample complexity of learning for networks of spiking neurons with nonlinear synaptic interactions.

We study networks of spiking neurons that use the timing of pulses to encode information. Nonlinear interactions model the spatial groupings of synapses on the neural dendrites and describe the computations performed at local branches. Within a theoretical framework of learning we analyze the question of how many training examples these networks must receive to be able to generalize well. Bounds for this sample complexity of learning can be obtained in terms of a combinatorial parameter known as the pseudodimension. This dimension characterizes the computational richness of a neural network and is given in terms of the number of network parameters. Two types of feedforward architectures are considered: constant-depth networks and networks of unconstrained depth. We derive asymptotically tight bounds for each of these network types. Constant depth networks are shown to have an almost linear pseudodimension, whereas the pseudodimension of general networks is quadratic. Networks of spiking neurons that use temporal coding are becoming increasingly more important in practical tasks such as computer vision, speech recognition, and motor control. The question of how well these networks generalize from a given set of training examples is a central issue for their successful application as adaptive systems. The results show that, although coding and computation in these networks is quite different and in many cases more powerful, their generalization capabilities are at least as good as those of traditional neural network models.

Action Potentials↗

PubMed1989

Expression of Lewis antigenic determinants in colorectal adenocarcinomas.

Expression of type 1 and type 2 chain Lewis antigens was studied in 32 rectal adenocarcinoma specimens; the results were correlated with the patients' Lewis phenotype and secretor status. In addition, the pattern of expression of these antigens was analyzed in adjacent and distant normal mucosa. We used an indirect immunofluorescence technique with p-phenylenediamine counterstaining (Oriol technique) and a panel of monoclonal antibodies directed against the different antigenic specificities. Normal distal colonic mucosa only expresses monofucosylated structures (Lea and X) arising from activity of the alpha 1-3,4-fucosyltransferase coded by the Le gene. Rectal adenocarcinomas also show Lea and X, but also reexpress blood group antigens ABH and exhibit difucosylated determinants (Leb and Y). The accumulation of mono- and difucosylated type 2 chain in neoplastic processes, independently of the Le and Se genes, could be due to the enzymes coded by reactivation of the H and X genes. Blood group antigens form a complex signal code, genetically regulated, which intervenes in differentiation, growth and cellular recognition processes, and which may undergo important modifications during malignant transformation. These alterations could be useful in the diagnosis and prognosis of some types of carcinoma.

Adenocarcinoma↗

PubMed2001

Genetic and environmental influences on orthographic and phonological skills in children with reading disabilities.

Data from identical and fraternal twins were analyzed to estimate the proportions of genetic and environmental influences on group deficits in accuracy and, when available, speed for printed word recognition and for related skills in phonological decoding (PD), orthographic coding (OC), and phoneme awareness (PA). In addition, bivariate genetic analyses were employed to estimate the degree of common genetic influence on group deficits across these different reading and language skills. About half of the group deficits in each of the skills were due to genetic influences, and the genetic origins were largely shared among the measures (r(g) = .53 - .99), except for those between OC and PA (r(g) = .28 - .39). Implications of the results are discussed for models of reading disability and remediation.

Adolescent↗

PubMed1997

[Profile of self-medication in Brazil].

INTRODUCTION: The data presented are part of a World Health Organization (WHO) multicenter study of self-medication in Latin America. Brazilian sites included: Belo Horizonte, Fortaleza, the city of S. Paulo and outlying locations. The objective was to characterize self-medication practices by analyzing drugs sought by consumers in pharmacies without a physician's prescription. MATERIAL AND METHOD: Drugs were classified according to the Anatomic Therapeutic Classification codes, and analyzed with respect to 1) intrinsic value; 2) recognition as an essential drug (by either WHO or Brazil); 3) number of active ingredients; and 4) requirement for prescription. RESULTS: Five thousand, three hundred and thirty-two (5,332) different drugs, with 785 distinct active ingredients were sought. Of these, 49.5% were fixed dose combinations, 53.0% were of little intrinsic value, 44.1% required a physician's prescription, 71.0% were not essential drugs, and 40.0% of requests were based on prior prescriptions from the physician. The drugs most requested were analgesics (17.3%), nasal descongestants (7.0%), antirheumatic anti-inflammatory drugs (5.6%), and systemic anti-infective drugs (5.6%). CONCLUSIONS: Self-medication in Brazil reflects the needs and habits of the population. It is strongly influenced by physician's-prescribing habits and by the inadequate selectivity of the Brazilian pharmaceutical market.

Adult↗

PubMed1995

Digital signal processing of the phonocardiogram: review of the most recent advancements.

The objective of the present paper is to provide a detailed review of the most recent developments in instrumentation and signal processing of digital phonocardiography and heart auscultation. After a short introduction, the paper presents a brief history of heart auscultation and phonocardiography, which is followed by a summary of the basic theories and controversies regarding the genesis of the heart sounds. The application of spectral analysis and the potential of new time-frequency representations and cardiac acoustic mapping to resolve the controversies and better understand the genesis and transmission of heart sounds and murmurs within the heart-thorax acoustic system are reviewed. The most recent developments in the application of linear predictive coding, spectral analysis, time-frequency representation techniques, and pattern recognition for the detection and follow-up of native and prosthetic valve degeneration and dysfunction are also presented in detail. New areas of research and clinical applications and areas of potential future developments are then highlighted. The final section is a discussion about a multidegree of freedom theory on the origin of the heart sounds and murmurs, which is completed by the authors' conclusion.

Coronary Disease↗

PubMed1995

New instruments, bone liners, and tray for finger joint arthroplasty.

Titanium circumferential grommets have been developed for finger joint arthroplasty that fit on the base of the silicone implant stems to protect the flexible hinge from tearing and fracture. To facilitate grommet insertion, new intramedullary bone rasps have been devised with a reverse cutting tooth pattern, an extended shaft for an improved view of the surgical field, and a redesigned cutting head to allow for grommet insertion. Surgical accessibility and ease of recognition have been facilitated by the development of color-coded sizers. All of the instruments necessary for finger joint surgery are available in a molded tray that has also been redesigned with a transparent lid and clearly labeled compartments for accurate determination of instruments and implant sizers.

Equipment Design↗

PubMed2002

[Study on the Relationship between susceptibility of stomach neoplasm cancer and polymorphism of inducible nitric oxide synthase gene].

OBJECTIVE: To study the relationship between polymorphism of inducible Nitric Oxide Synthase (iNOS) gene and the susceptibility of intestinal type stomach cancer and stomach cardia cancer in Chinese people. METHODS: A community-based case-control study was designed. Ninety-three intestinal type of stomach cancer and 50 stomach cardia cancer patients with endoscopy and pathology diagnosis were identified as cases. Two hundred and forty-six controls served as controls. RESULTS: C-->T polymorphism was found in exon 16 of iNOS gene, which changed the coding amino acid from serine to leucine, and formed a recognition site identified by Tsp 509 I restriction enzyme (we called it C-->T polymorphism). The T allele gene frequency in the control group was 13.21%. No statistically significant difference was found between C-->T polymorphism alone and the increased susceptibility to intestinal stomach cancer or stomach cardia cancer. A significant type 2 multiplicative interaction was found in increasing both the risk of intestinal stomach cancer and stomach cardia cancer when both C-->T polymorphism and tobacco smoking exposure existed. An additive interaction model, which showed statistically significant difference, was found to increase only the risk of stomach cardia cancer when CagA antibody shared negative but C-->T polymorphism occurred. CONCLUSION: C-->T polymorphism of iNOS gene was considered as one of the possible susceptible genes, which specifically increased the risk of tobacco-related but CagA negative types of intestinal stomach cancer and stomach cardia cancer.

Antibodies, Bacterial↗

PubMed1983

Antigen and MHC restriction specificity of two types of cloned male-specific T cell lines.

Two types of H-Y antigen-specific cloned T cell lines were established. Clone 2-1 is an IAb restricted proliferating T cell line and clone 10-2 is an H-2Db restricted proliferating and cytotoxic T cell line. Clone 2-1 proliferated in response to H-Y antigen with an IAb restriction in the absence of IL 2. IAb mutant B6.C-H-2bm12 (bm12) mice did not stimulate this clone. This defect may be the cause of the unresponsiveness to H-Y antigen with cytotoxic T lymphocytes (CTL) in bm 12 mice (i.e., the failure of activation of H-Y-specific helper T cells). Although (B10.A X bm12)F1 mice are known to show functional complementation, as demonstrated by the presentation of insulin to helper T cells and the H-Y-specific CTL response, the F1 male cells could not stimulate this clone. The IA determinant restricting H-Y antigen presentation to helper T cells and/or the H-Y antigenic determinant seems to differ between C57BL/6 (B6) and the F1 mice. Monoclonal anti-IAb antibodies but not anti-H-Y antibodies blocked the proliferation of this clone. The clone had no cytotoxic activity unless Con A was added to the cytotoxicity assay culture. Clone 10-2 proliferated in response to H-Y antigen with an H-2Db restriction. Proliferation was not observed unless specific stimulator cells and IL 2 were supplied to the culture; IL 2 alone could not support this clone. The clone did not respond to male cells from the H-2Db mutant B6.C-H-2bm14 (bm14). The clone had cytotoxic activity against male H-2Db+ cells but not against male bm14 cells. This evidence indicates that the mutation of bm14 occurred in the structural gene coding for a molecule on which a determinant restricting the recognition of H-Y antigen by B6 CTL exists. The phenotypes of clone 2-1 were Thy-1.2+, Ly-1.2-, Ly-2.2-, IAb-, and H-2Kb+, and the phenotypes of clone 10-2 were Thy-1.2+, Ly-1.2-, Ly-2.2+, IAb-, and H-2Kb+.

Animals↗

PubMed2005

One neuron--multiple receptors: increased complexity in olfactory coding?

Olfaction--the sense of smell--is responsible for detecting molecules of immense structural variety. Precise recognition of such diverse stimuli requires a massive receptor repertoire. This functional challenge has been met by simultaneous expression of a multitude of odor-detecting receptors that all belong to the superfamily of heterotrimeric GTP-binding protein (G protein)-coupled receptors. Studies conducted over the past decade have led to the assumption that an individual olfactory sensory neuron expresses only a single odorant receptor, consequently giving rise to the "one receptor-one neuron" hypothesis. This idea is attractive because of its simplicity and has served as the basis for models of olfactory coding. However, recent reports regarding Drosophila have found exceptions to the rule that could have important implications for the logic of olfactory coding.

Animals↗

PubMed1998

VHMPT: a graphical viewer and editor for helical membrane protein topologies.

MOTIVATION: Lacking structures resolved at atomic resolution, the great majority of membrane proteins have typically been depicted in a schematic two-dimensional (2D) topology consisting of putative transmembrane domains predicted from hydropathy plots. As more and more sequences of membrane proteins become available from genome projects, there is a need to automate the process of generating the schematic topology while allowing important information, such as the individual amino acid and the extent to which it is conserved in evolution, to be conveniently inspected. We addressed this need by developing a program called VHMPT. RESULTS: VHMPT (a graphical V iewer and editor for H elical line M embrane P rotein T opologies) can automatically generate a schematic 2D topology for a protein with transmembrane helices. Through an interactive graphical interface, VHMPT allows users to modify the layout of the generated topology, label specific amino acid or amino acid groups, and annotate with arrows and texts. Given a multiple sequence alignment file, VHMPT can also color code a normalized conservation score for each amino acid on the generated topology, allowing ready visual recognition of highly conserved (or variable) topological regions. VHMPT is written in Tcl/Tk and can run on platforms that have installed the Tcl/Tk interpreter. AVAILABILITY: The source code and a user manual for VHMPT are available for download at http://www. ibms.sinica.edu.tw/mjhwang/vhmpt. CONTACT: mjhwang@mail.ibms.sinica.edu.tw

Computational Biology↗

PubMed1993

The early and intermediate precursor lesions of tumor progression in the melanocytic system: common acquired nevi and atypical (dysplastic) nevi.

Intermediate lesions of melanocytic tumor progression are potential precursors, simulants, and risk markers of melanoma. The clinical, public health, and biologic significance of intermediate lesions warrants their continued recognition and study, although improved schemata for their clinical and histological coding are needed. Blurred boundaries are inherently problematic to the categorization of lesions occurring along a stepwise pathway of increasing clinical and histological atypia. Nevertheless, the concepts of melanocytic dysplasia and of radial growth phase (in situ and microinvasive) melanoma are important to the classification of intermediate lesions of melanocytic tumor progression. Conceptually, these lesions are clearly separable from early and late lesions and from one another, and there is evidence that criteria distinguishing them can be reproducibly applied. Analysis of these intermediate lesions suggests that they represent responses to events (perhaps mutational) induced by ultraviolet light in constitutionally hypersensitive individuals, supporting epidemiological data that implicate sunlight as an etiologic agent for most melanomas. The continuing rigorous application of the methodologies of epidemiology and basic science to the study of these lesional steps will likely lead to the recognition of biologic markers to better distinguish benign from malignant melanocytic lesions.

Adult↗