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At least 271 records · Page 15Linked to original sources
PubMed1991

Classification of lung cancer: first experiences with the new TNM classification (4th edition).

In January 1987, the 4th edition of the TNM classification for malignant lung tumours by the International Union Cancer (UICC) came into effect. Thus, for the first time, a uniform worldwide staging system for lung cancer became available. In order to validate the new TNM definitions for lung cancer the data of 3,000 patients were analysed prospectively. Several items were examined: 1) the agreement between clinically (TNM) and pathologically (pTNM) confirmed classification; 2) the value of the various diagnostic techniques estimating the pathologically confirmed classification; 3) the influence of the TNM definitions on separating distinct prognostic groups. With regard to the primary tumour (T), clinical and pathological classifications were identical in 64%; for lymph node involvement (N) the agreement was 48%; for distant metastases it was 90% and for the stages it was 55%. As for the primary tumour (T) the accuracy of radiography (59%) was nearly identical to computed tomography (58%). Both techniques were less precise in determining the extent of lymph node involvement (computed tomography 50%, radiography 43%, correct assessments). The statistically significant differences in prognosis for the various T-, N- and M-categories as well as for the stages could be confirmed. By the new 1987 TNM definitions (4th edition) for lung cancer international conformity became feasible as well as practical, and the improvement in its prognostic relevance provided, therefore, a more reliable basis for establishing guidelines for individual oncological concepts of therapy.

Carcinoma, Bronchogenic↗
PubMed1999

Psoriasis upregulated phorbolin-1 shares structural but not functional similarity to the mRNA-editing protein apobec-1.

Earlier studies of psoriatic and normal primary keratinocytes treated with phorbol 12-myristate-1-acetate identified two low-molecular-weight proteins, termed phorbolin-1 (20 kDa; pI 6.6) and phorbolin-2 (17.6 kDa; pI 6.5). As a first step towards elucidating the role of these proteins in psoriasis, we report here the molecular cloning and chromosomal mapping of phorbolin-1 and a related cDNA that codes for a protein exhibiting a similar amino acid sequence. The phorbolins were mapped to position 22q13 immediately centromeric to the c-sis proto-oncogene. Transient expression of the phorbolin-1 cDNA in COS cells and by in vitro transcription/translation, yielded polypeptides that comigrated with phorbolins-1 and -2. Comparative sequence analysis revealed 22% overall identity and a similarity of 44% of the phorbolins to apobec-1, the catalytic subunit of the mammalian apolipoprotein B mRNA editing enzyme; however, recombinant-expressed phorbolin-1 exhibited no cytidine deaminase activity, using either a monomeric nucleoside or apolipoprotein B cRNA as substrate, and failed to bind an AU-rich RNA template. Whereas the precise function of the phorbolins remains to be elucidated, the current data suggest that it is unlikely to include a role in the post-transcriptional modification of RNA in a manner analogous to that described for apobec-1.

APOBEC-1 Deaminase↗
PubMed2006

Role of polyamines derived from arginine in differentiation and proliferation of human blood cells.

L-Arginine is a precursor of polyamine, nitric oxide (NO), creatine, and agmatine and is essential for the differentiation and proliferation of blood cells, although the precise biological role of L-arginine is unclear. We have recently reported that the depletion of L-arginine in cultured medium prevented both proliferation and differentiation of blood cells (Shima et al., Blood First Edition Paper, October 6, 2005; DOI 10.1182). Since one of metabolic products of L-arginine in the cells is polyamine that associates with cell differentiation and proliferation, the effects of L-arginine on the human K562 cell line and human cord blood-derived CD34 positive cells were investigated by focusing on polyamines such as putrescine, spermidine, and spermine in the present study. When polyamines were added to the culture medium in the absence of L-arginine, the cells did not grow or differentiate well. However, when intracellular polyamines were depleted using ornithine decarboxylase inhibitor, alpha-difluoromethylornithine (DFMO), the proliferation and differentiation of K562 cells to erythrocytes were reduced even in the presence of L-arginine. Moreover, in the presence of DFMO, cell differentiation and proliferation were recovered by the addition of putrescine or spermidine in the presence of L-arginine. Accordingly, it was demonstrated that polyamines are essential for the proliferation and differentiation of the blood cells as the metabolites of L-arginine and the externally added polyamines are also effective by being taken up through polyamine transporter.

Antigens, CD34↗
PubMed2004

[Menopause in 2004: "hormone replacement therapy" is not what it used to be anymore].

PURPOSE: The data concerning post-menopausal hormone replacement therapy (HRT) were recently completely modified. The aim of this review is to present the last studies about post-menopausal HRT and to describe new alternatives to this treatment. CURRENT KNOWLEDGE AND KEY POINTS: In May 2002, the women's health initiative (WHI) trial of post-menopausal HRT was interrupted earlier than expected. The studied hormonal formulation in this arm of the WHI trial was the association of conjugated equine estrogens and medroxyprogesterone. The reason for termination was an increased risk of breast cancer and myocardial infarction in the hormone-therapy group. Later, reports confirmed that this type of HRT could not be used any more for the primary prevention of coronary heart disease even if the absolute risk remained low. There is an increased risk for venous thromboembolism with post-menopausal estroprogestative replacement. This risk does not seem to exist with transdermal estrogens. The other WHI findings concerned the lack of protection against dementia and cognitive decline. On the contrary, osteoporotic hip fractures and colorectal cancers were reduced in the treated group. In April 2004, the estrogen only arm of the same WHI study was also prematurely interrupted because of an increase in the incidence of stroke. The risk of breast cancer was on the contrary not increased after 6.8 years, raising the question of the eventual role of progestins. PERSPECTIVES: The impact of the WHI trial on clinical practice was very important since then. The "Agence Francaise de sécurité sanitaire des produits de santé" (AFSSAPS) edited in May 2004 a public recommendation limiting indication for HRT to patients with severe climacteric symptoms. The treatment must now be prescribed for the shortest time and at the minimal dose. The patient has to be precisely informed about the risks with HRT and the practitioner has to re-evaluate his prescription annually. Hormonal or non-hormonal alternatives have also to be considered as phytoestrogens and tibolone for hot flashes, and raloxifene and diphosphonates for osteoporosis prevention. In any case, a healthy diet, exercise and smoking cessation should be encouraged.

Breast Neoplasms↗
PubMed2026

Prime assembly with linear DNA donors enables large genomic insertions.

Targeted insertion of large DNA fragments has promising applications for genome engineering and gene therapy1,2. Twin prime-editing guide RNAs have enabled relatively large insertions, but the efficiency remains low for insertions greater than 400 base pairs3-6. Here we describe a prime assembly (PA) approach for the insertion of large DNA donor fragments, of which the ends are designed to overlap with the flaps generated by twin prime editing (twinPE). We used PA to insert one or multiple overlapping DNA fragments, with total insertion sizes ranging from 0.1 kb to 11 kb. An inhibitor of non-homologous end joining enhanced both the efficiency and precision of insertions. PA relies on DNA templates that are easily produced, does not require co-delivery of exogenous DNA-dependent DNA polymerases and proceeds in non-cycling cells, suggesting independence from canonical homology-directed repair pathways. Our study demonstrates that PA can initiate Gibson-like assembly in cells to generate gene insertions without double-stranded DNA breaks, recombinases or homology-directed repair.

Animals↗
PubMed2000

Aminoacyl-tRNA synthesis.

Aminoacyl-tRNAs are substrates for translation and are pivotal in determining how the genetic code is interpreted as amino acids. The function of aminoacyl-tRNA synthesis is to precisely match amino acids with tRNAs containing the corresponding anticodon. This is primarily achieved by the direct attachment of an amino acid to the corresponding tRNA by an aminoacyl-tRNA synthetase, although intrinsic proofreading and extrinsic editing are also essential in several cases. Recent studies of aminoacyl-tRNA synthesis, mainly prompted by the advent of whole genome sequencing and the availability of a vast body of structural data, have led to an expanded and more detailed picture of how aminoacyl-tRNAs are synthesized. This article reviews current knowledge of the biochemical, structural, and evolutionary facets of aminoacyl-tRNA synthesis.

Animals↗
PubMed1999

History of prosthetic grafts.

The evolution of vascular surgery during the past five decades has established what was once controversial to be mandate, what was never dreamed of as debatable, and the vast body of knowledge yet to be unraveled--but requiring clinical application--as currently controversial. Controversy results when dissimilar therapies yield comparable outcomes, despite having been reached by different pathways. Scientific methods to dissect the precise mechanisms of cause/effect, and not reliance on associations, are necessary to resolve controversies that may contribute to inappropriate conclusions. Much effort has been expended by vascular surgeons in the search for an ideal vascular conduit. This edition of Seminars explores the status, past, present, and future, of a variety of graft materials. Future modifications and availability of the "ideal graft" will evolve as challenges are met.

Blood Vessel Prosthesis↗
PubMed2006

[Clinical value of the sixth edition TNM stages analysing prognosis of colorectal cancer].

OBJECTIVES: To study the clinical value analyzing of colorectal cancer prognosis by the Sixth Edition TNM Stages. METHODS: 5481 cases with colorectal cancer and treated by operational methods, were collected. All the cases were separately staged by the Fifth Edition or Sixth Edition TNM Stages standards. The 5-year survival rates were analyzed by the life table method. RESULTS: The 5-year survival rates of the Fifth Edition TNM Stages of I, II, III and IV were 80.1%, 68.0%, 40.5% and 9.8% respectively. The 5-year survival rates of the Sixth Edition TNM Stages of II(A) and II(B) were 71.6% and 66.4% respectively, and of the stages III(A), III(B) and III(C) were 46.2%, 40.1% and 28.3% respectively. There were statistical differences among the sub-stages II and III, P < 0.05. CONCLUSION: The Sixth edition TNM Stages laid more stress on effect of the local infiltration depths and lymphatic metastasis in the prognosis of colorectal cancer, therefore, the stages were more fine, to analyze prognosis of the colorectal cancer were more precise. It is high clinical value for the individual complex treatment with every sub-stages.

Adenocarcinoma↗
PubMed2025

Cardiac hypertrophy at the crossroads: Mechanistic insights and emerging multimodal therapeutic strategies.

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, accounting for approximately 17.9 million deaths annually. Among their diverse manifestations, cardiac hypertrophy is a clinically significant condition that predisposes patients to heart failure, arrhythmias, and and sudden cardiac death. Clinically, hypertrophy can be classified into three forms: physiological (adaptive) hypertrophy, which supports cardiac performance and is reversible, pathological hypertrophy most often secondary to hypertension, valvular disease, hemodynamic stress, or sustained neurohumoral activation; and hypertrophic cardiomyopathy (HCM) represents a primary genetic disorder, most often caused by mutations in sarcomeric proteins. These distinct etiologies have important therapeutic implications, as they determine how efficiently pharmacological agents can target underlying mechanisms. Conventional pharmacological treatments are widely used in clinical practice, yet they provide limited reversal of established remodeling. This therapeutic gap has driven the development of innovative modalities such as RNA-based therapeutics, exosome-mediated interventions, stem cell-derived therapies, and genome-editing technologies, which aim to modulate maladaptive signaling and restore myocardial integrity. This review integrates clinical perspectives with mechanistic insights, delineating the drivers of pathological hypertrophy while evaluating both established therapies and emerging strategies that hold promise for precision cardiology and improved patient outcomes.

Humans↗
PubMed2003

Digital photography and the assessment of therapeutic results after bleaching procedures.

UNLABELLED: The therapeutic outcome of tooth-bleaching procedures can be assessed by different methods, one of them being digital photography. However, none of the methods seems to be perfect. In this overview factors are discussed that have an influence on color rendition and image brightness in (digital) photography. A photographic procedure is proposed that results in comparable images. Beginning with a short description of some digital cameras currently used in dental photography, the article discusses the influence of light and camera technology on image brightness and color rendition in detail. Even if a highly standardized procedure is performed, there remain factors that affect color and brightness that cannot be excluded completely. Therefore, a photographic procedure is proposed that includes a piece of gray card in the picture as a neutral reference object. In this way, color casts can be eliminated and image brightness can be fine tuned using a standard image-editing program (Adobe Photoshop, Adobe Systems Incorporated, San Jose, CA, USA) before the relevant color values are metered by the same software. CLINICAL SIGNIFICANCE: A photographic procedure using digital cameras is proposed that is relatively simple and sufficiently precise to allow the assessment of the therapeutic outcome of tooth-bleaching procedures.

Color↗
PubMed2025

An elegant co-transformation strategy for recalcitrant wheat using morphogenic regulators.

Common wheat (Triticum aestivum L.) is a vital global crop, but many elite cultivars remain recalcitrant to genetic transformation, hindering functional genomics and crop improvement. Here, we developed an efficient co-transformation strategy for recalcitrant wheat varieties (e.g., Aikang58 and Xinong979) using the morphogenic gene mTaGRF4-TaGIF1. This approach entails mixing Agrobacterium tumefaciens cultures carrying two separate vectors: a standard gene-of-interest (GOI) vector (containing a selectable marker) and a gene-of-co-transformation vector (GOC, expressing mTaGRF4-TaGIF1 without a selectable marker). Co-transformation enhanced regeneration efficiency to ~37.38% in AK58, a marked improvement over conventional methods, enabling consistent recovery of transgenic plants. Among regenerants, ~63.25% carried both GOI and GOC (GOI&GOC), while ~11.92% contained only the GOI. Only-GOI plants could also be obtained through progeny segregation from GOI&GOC lines. We successfully generated GUS- and RUBY-expressing transgenic lines, as well as CRISPR-Cas9-edited mutants targeting Q and Ph1 genes, confirming the method's efficacy for both gain-of-function and genome editing application. Furthermore, the strategy was successfully extended to another recalcitrant variety Xinong979, demonstrating its potential for broad applicability. Unlike existing methods dependent on complex excision systems or tissue-specific promoters, our co-transformation methodology significantly simplifies both vector design and procedural workflow while maintaining high efficiency. Collectively, these findings establish a technically advanced yet operationally simplified transformation platform that addresses the long-standing challenge of genetic transformation in recalcitrant wheat varieties, providing researchers with a powerful tool for functional genomics studies and accelerating precision breeding programs in elite wheat cultivars.

Triticum↗
PubMed1997

The genomic organization of guide RNA genes in kinetoplastid protozoa: several conundrums and their solutions.

The guide RNA (gRNA) paradigm states that the uridine (U) insertion/deletion type of RNA editing is mediated by short 3' uridylylated gRNAs that are complementary to specific blocks of mature edited sequence. These gRNAs contain the edited sequence information in the form of guiding purine residues that can base pair with the inserted U's and do not base pair with encoded U's that are to be deleted. The minicircle gRNA genes in trypanosomatids are localized at specific sites within the variable region, with the number and the precise localization of genes also being species-specific. The total number of minicircle sequence classes and thereby minicircle-encoded gRNAs varies greatly between species and even between different strains of the same species, with the greatest number being in the trypanosome species. Several conundrums which appeared to raise problems for the gRNA paradigm arose during comparative analysis of minicircle gRNA gene organization. The solution of these conundrums has led to a better understanding of the function and evolution of this RNA modification phenomenon.

Animals↗
PubMed2003

Median-based robust algorithms for tracing neurons from noisy confocal microscope images.

This paper presents a method to exploit rank statistics to improve fully automatic tracing of neurons from noisy digital confocal microscope images. Previously proposed exploratory tracing (vectorization) algorithms work by recursively following the neuronal topology, guided by responses of multiple directional correlation kernels. These algorithms were found to fail when the data was of lower quality (noisier, less contrast, weak signal, or more discontinuous structures). This type of data is commonly encountered in the study of neuronal growth on microfabricated surfaces. We show that by partitioning the correlation kernels in the tracing algorithm into multiple subkernels, and using the median of their responses as the guiding criterion improves the tracing precision from 41% to 89% for low-quality data, with a 5% improvement in recall. Improved handling was observed for artifacts such as discontinuities and/or hollowness of structures. The new algorithms require slightly higher amounts of computation, but are still acceptably fast, typically consuming less than 2 seconds on a personal computer (Pentium III, 500 MHz, 128 MB). They produce labeling for all somas present in the field, and a graph-theoretic representation of all dendritic/axonal structures that can be edited. Topological and size measurements such as area, length, and tortuosity are derived readily. The efficiency, accuracy, and fully-automated nature of the proposed method makes it attractive for large-scale applications such as high-throughput assays in the pharmaceutical industry, and study of neuron growth on nano/micro-fabricated structures. A careful quantitative validation of the proposed algorithms is provided against manually derived tracing, using a performance measure that combines the precision and recall metrics.

Algorithms↗
PubMed2025

Validation of caprine H11 and the Rosa26 platform for transgene integration via CRISPR-based system: investigations on stable transgene expression and genetic biosafety.

CRISPR/Cas9 technology is an efficient tool for site-specific livestock gene editing. However, to minimize potential disruption of host genome function, exogenous genes should be integrated into well-characterized genomic loci, such as H11 or Rosa26, which have been empirically validated for stable transgene expression. This study established a multi-dimensional assessment system to evaluate the biological applicability of the H11 locus and the widely used Rosa26 targeting platform as sites for targeted integration of exogenous genes in goats. Donor cells carrying the enhanced green fluorescent protein (EGFP) reporter gene at the H11 and Rosa26 loci were generated via CRISPR/Cas9-mediated homology-directed repair; this was followed by somatic cell nuclear transfer to produce transgenic cloned embryos and healthy offspring. Multi-dimensional analyses revealed the following. At the cellular level, there was stable and efficient EGFP expression at integration sites, with donor cells maintaining normal cell cycle progression, proliferation capacity, and apoptosis levels, and with no alterations in the transcriptional integrity of adjacent genes. At the embryonic level, there was sustained EGFP expression across pre-implantation embryonic stages, with developmental metrics statistically indistinguishable from wild-type embryos. Finally, at the individual level, cloned offspring exhibited growth phenotypes consistent with wild-type counterparts, and EGFP showed broad-spectrum expression in eight tissues. This study establishes the first CRISPR/Cas9-based crossscale (cellular-embryonic-individual) validation in goats, demonstrating that the H11 and Rosa26 loci support efficient and stable transgene integration in goats. These results provide a precise and predictable technical framework for livestock genetic improvement.

Animals↗
PubMed2004

Locating responsibility: the Sphere Humanitarian Charter and its rationale.

Criticised by some as a technical initiative that neglects core principles, Sphere was seen by its originators precisely as an articulation of principle. The Humanitarian Charter was the main vehicle through which this was expressed, but its relationship to the Minimum Standards has remained a matter of uncertainty. Specifically, it was unclear in the original (1999) edition of Sphere how the concept of rights informed the Minimum Standards. The revised (2004) edition goes some way to clarifying this in the way the standards are framed, yet the link between the standards and the charter remains unclear. The concern with the quality and accountability of humanitarian assistance, which motivated the attempt to establish system-wide standards through the Sphere Project, was accompanied by a desire to establish such actions in a wider framework of legal and political responsibility. In part, this reflects the conditional nature of the undertaking that agencies make when they adopt Sphere. This aspect of the charter has been neglected, but it is fundamental to an understanding of the standards and their application. This paper considers the rationale of the Sphere Humanitarian Charter and the conceptual model that underpins it. It discusses the relationship between the charter and the Minimum Standards, and the sense in which the latter are properly called "rights-based" (explored further in a related paper herein by Young and Taylor). The author was closely involved in the conception and drafting of the charter, and this paper attempts to convey some of the thinking that lay behind it.

Altruism↗
PubMed2026

Gene therapy for genodermatoses at the crossroads of innovation and clinical translation.

Inherited genodermatoses are a heterogeneous group of rare monogenic disorders. Among these, epidermolysis bullosa (EB) and ichthyoses represent paradigmatic disorders characterized by severe skin fragility and hyperkeratosis, respectively, and impaired barrier function, often with profound effects on quality of life and systemic health. Current management remains largely palliative, underscoring the urgent need for disease-modifying therapies. Over the past 2&#xa0;decades, advances in epithelial stem cell biology, vector engineering and genome editing technologies have transformed the therapeutic landscape for genodermatoses. Ex vivo gene therapy has provided the first proof that genetically corrected epidermal stem cells can achieve long-term tissue regeneration in EB skin patients, establishing a new paradigm for regenerative medicine. In parallel, the emergence of programmable genome engineering platforms, including CRISPR/Cas nucleases, base editors and prime editors, have enabled increasingly precise strategies for mutation-specific correction in both recessive and dominant disorders. Furthermore, the development of in vivo topical approaches is expanding the possibility of directly targeting the skin. Despite these advances, substantial translational barriers continue to limit broad clinical implementation. Efficient and durable targeting of epidermal stem cells within a highly regenerative tissue, together with safe delivery across the skin barrier, stringent control of off-target activity, scalable manufacturing and demonstration of long-term safety, remain major challenges for the clinical translation of these approaches. In this Review, we discuss the current state of gene therapy for genodermatoses, highlighting key clinical milestones, emerging genome editing technologies and next-generation delivery systems. We further examine the biological and regulatory challenges that need to be overcome to bridge the gap between experimental innovation and clinically accessible therapies for patients with inherited skin diseases.

epidermolysis bullosa (EB)↗
PubMed1998

Linkage map of Escherichia coli K-12, edition 10: the physical map.

A physical map, EcoMap10, of the now completely sequenced Escherichia coli chromosome is presented. Calculated genomic positions for the eight restriction enzymes BamHI, HindIII, EcoRI, EcoRV, BglI, KpnI, PstI, and PvuII are depicted. Both sequenced and unsequenced Kohara/Isono miniset clones are aligned to this calculated restriction map. DNA sequence searches identify the precise locations of insertion sequence elements and repetitive extragenic palindrome clusters. EcoGene10, a revised set of genes and functionally uncharacterized open reading frames (ORFs), is also depicted on EcoMap10. The complete set of unnamed ORFs in EcoGene10 are assigned provisional names beginning with the letter "y" by using a systematic nomenclature.

Chromosome Mapping↗
PubMed2001

Using skeleton-based tracking to increase the reliability of optical motion capture.

Optical motion capture provides an impressive ability to replicate gestures. However, even with a highly professional system there are many instances where crucial markers are occluded or when the algorithm confuses the trajectory of one marker with that of another. This requires much editing work on the user's part before the complete animation is ready for use. In this paper, we present an approach to increasing the robustness of a motion capture system by using an anatomical human model. It includes a reasonably precise description of the skeleton's mobility and an approximated envelope. It allows us to accurately predict the 3-D location and visibility of markers, thus significantly increasing the robustness of the marker tracking and assignment, and drastically reducing--or even eliminating--the need for human intervention during the 3-D reconstruction process.

Algorithms↗