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PubMed2026

Sec and Tat Mediated Secretion Safeguards Mycobacterium tuberculosis Membrane Homeostasis.

Protein secretion is essential for the growth and virulence of Mycobacterium tuberculosis, yet the organization and function of its secretion pathways remain poorly understood. We reviewed the existing literature, combined it with systematic queries, and finalized annotations based on experimental data and computational predictions to compile a curated list of 92 secretory components and 198 reactions involved in Sec, twin-arginine translocation (Tat), and ESX pathways. Using CRISPRi, targeted depletion of SecA1 or TatAC impaired both in vitro growth and ex vivo survival. Label-free quantitative secretome analysis revealed decreased export of substrates dependent on SecA1 and TatAC, with enrichment of cytosolic proteins in culture filtrates, indicating increased membrane dysbiosis. Membrane proteomics showed elevated levels of proteins engaged in intermediary and lipid metabolism, while proteins associated with the cell wall and cell processes decreased, suggesting weakened membrane integrity. Loss of SecA1 or TatAC increased membrane permeability, with the effect being more pronounced in the case of TatAC, and caused structural abnormalities seen under electron microscopy. Overall, our integrated multi-omics and functional genetics studies demonstrate that the SecA1 and Tat pathways are essential for maintaining membrane homeostasis in Mycobacterium tuberculosis. These results suggest that essential secretory proteins may be promising targets for therapeutic intervention.

Mycobacterium tuberculosis↗
PubMed1999

Genetics of allergy and asthma.

LEARNING OBJECTIVES: This article summarizes the latest information regarding the role of genetic influences in the development of allergic disorders and asthma and reviews our current information on some of the most likely genes responsible for these conditions. After reading this article, the reader will have a better understanding of the current molecular biologic techniques that are being used to understand complex genetic disorders such as allergies and asthma. The reader should understand the value of how this genetic insight will lead to the recognition of the presence of specific subtypes of these disorders that require unique therapeutic interventions. This information can also be used to identify genetically at risk children and thereby offer earlier intervention. Finally, understanding the genetic causes of allergies and asthma will lead to the development of the next--hopefully curative--generation of asthma and allergy therapeutics. DATA SOURCES: A detailed literature search was conducted. Studies considered relevant, well performed, and appropriately controlled were used. Only human studies are included and only the English language literature was reviewed. Some of the information presented is based on the author's own research experience. STUDY SELECTION: Material was only taken from peer-reviewed journals and appropriate reviews. RESULTS AND CONCLUSIONS: Asthma and allergic diseases are examples of disorders having an unmistakable genetic predisposition, but in the absence of a classic Mendelian inheritance pattern. These "complex" genetic disorders are caused by the interactions of multiple interacting genes some having protective value and some contributing to disease development and with each gene having its own variable tendency to be expressed. In addition, these disorders require the presence of appropriate environmental triggers for their expression. One approach to identifying the genetic basis for these conditions is to perform a genome-wide search in which the location of the disease-causing gene on a human chromosome is identified and nearby genes that may be responsible are subsequently identified. An alternative approach to identifying heritable components to asthma and allergy is to evaluate disordered structure or regulation within genes known to be involved in these disorders. Using these approaches, studies have suggested that genes within the cytokine gene cluster on chromosome 5 (including interleukins-3, -4, -5, -9, and -13), chromosome 11 (the beta chain of the high affinity IgE receptor), chromosome 16 (the IL-4 receptor), and chromosome 12 (stem cell factor, interferon-gamma, insulin growth factor, and Stat 6 [IL-4 Stat]) may contribute to asthma and allergy development. In addition, data support involvement of genes involved in antigen-presentation (MHC class II genes) and T cell responses (the T cell receptor alpha chain). Finally, disease-contributing alleles may be present on genes for the beta-adrenergic receptor, 5-lipoxygenase, and leukotriene C4 synthase.

Antigen Presentation↗
PubMed2003

Anterior tongue cancer: age is not a predictor of outcome and should not alter treatment.

BACKGROUND: Mucosal head and neck cancers usually occur in older males after years of smoking and alcohol abuse. Despite this, approximately 5% of cases occur in young adults. The aetiology remains unclear and the anterior tongue is a prevalent site. Prognosis has been reported as worse in young patients and some have proposed a more aggressive treatment approach. METHODS: Patients diagnosed with previously untreated anterior tongue squamous cell carcinoma and treated with curative intent were identified. Retrospective and prospective data were collected. Univariate and multivariate analyses were undertaken using Cox regression analysis. The outcome of patients treated with anterior tongue cancer using a cut-off age of 40 years was compared. RESULTS: Between 1980 and 2000, 106 males and 58 females with anterior tongue squamous cell carcinoma were treated at Westmead Hospital. Median follow up was 47 months (6-210 months). Twenty-two patients (13.4%) were aged </=40 years. Other than age, patient demographics, TNM stage and treatment approach were similar between the two groups. Eighty-one per cent had either a T1 or T2 primary. In total, 139 patients (84.8%) had surgery or surgery and radiotherapy. A total of 56 (34%) patients experienced a recurrent event, with nodal recurrence occurring most often as the first site (n = 33, 59%). Young patients had a higher recurrence rate (45.5% vs 32.4%; P = 0.23). Relapse-free survival at 5 years was 62% versus 81% (P = 0.27). Overall survival at 5 years was 65% versus 67% (P = 0.74). CONCLUSIONS: In keeping with recently published evidence, young age at diagnosis with anterior tongue cancer did not portend worse outcome. There is therefore currently no strong evidence to support a different treatment approach in young patients.

Adult↗
PubMed2026

Programmatic access to ICTV virus taxonomy through a public ontology API.

BACKGROUND: The International Committee on Taxonomy of Viruses (ICTV) is responsible for developing and maintaining a universal virus taxonomy. As the reference framework for organising the viral world, it is essential for virology and related fields. Despite its widespread use in research and public health, programmatic access to ICTV taxonomy has remained limited, posing challenges for integration, versioning, and interoperability across databases and bioinformatics resources requiring up-to-date virus taxonomy. FINDINGS: To address this, we developed a public and sustainable solution leveraging ontology-based APIs. All available ICTV Master Species List (MSL) releases, from MSL1 to MSL41, were transformed into a unified, semantically structured ontology comprising more than 195,000 current and historical entities and deployed through the Ontology Lookup Service (OLS). The ontology is automatically rebuilt and republished whenever a new MSL release becomes available. Complementary ICTV-NCBI mappings and helper libraries support integration into downstream systems. CONCLUSIONS: Together, these resources enable, for the first time, public programmatic retrieval of current and historical ICTV taxon names, taxonomic relationships, metadata, and persistent identifiers through stable endpoints, including resolution of former taxonomic terms to their current accepted taxon or taxa and retrieval of taxon histories across releases. More broadly, this work illustrates a general strategy for transforming structured biological datasets into semantically enriched graph resources exposed through scalable public APIs. These developments enhance interoperability, reduce manual curation, and support FAIR-aligned taxonomic data management in virology and pandemic preparedness.

API↗
PubMed1994

The Ribosomal Database Project.

The Ribosomal Database Project (RDP) is a curated database that offers ribosome-related data, analysis services, and associated computer programs. The offerings include phylogenetically ordered alignments of ribosomal RNA (rRNA) sequences, derived phylogenetic trees, rRNA secondary structure diagrams, and various software for handling, analyzing and displaying alignments and trees. The data are available via anonymous ftp (rdp.life.uiuc.edu), electronic mail (server/rdp.life.uiuc.edu) and gopher (rdpgopher.life.uiuc.edu). The electronic mail server also provides ribosomal probe checking, approximate phylogenetic placement of user-submitted sequences, screening for chimeric nature of newly sequenced rRNAs, and automated alignment.

Animals↗
PubMed1996

The Ribosomal Database Project (RDP).

The Ribosomal Database Project (RDP) is a curated database that offers ribosome-related data, analysis services and associated computer programs. The offerings include phylogenetically ordered alignments of ribosomal RNA (rRNA) sequences, derived phylogenetic trees, rRNA secondary structure diagrams and various software for handling, analyzing and displaying alignments and trees. The data are available via anonymous ftp (rdp.life.uiuc.edu), electronic mail (server@rdp.life.uiuc.edu), gopher (rdpgopher.life.uiuc.edu) and World Wide Web (WWW)(http://rdpwww.life.uiuc.edu/). The electronic mail and WWW servers provide ribosomal probe checking, screening for possible chimeric rRNA sequences, automated alignment and approximate phylogenetic placement of user-submitted sequences on an existing phylogenetic tree.

Computer Communication Networks↗
PubMed1997

The RDP (Ribosomal Database Project).

The Ribosomal Database Project (RDP) is a curated database that offers ribosome-related data, analysis services and associated computer programs. The offerings include phylogenetically ordered alignments of ribosomal RNA (rRNA) sequences, derived phylogenetic trees, rRNA secondary structure diagrams, and various software for handling, analyzing and displaying alignments and trees. The data are available via anonymous FTP (rdp.life.uiuc.edu), electronic mail (server@rdp.life.uiuc.edu), gopher (rdpgopher.life.uiuc.edu) and WWW (http://rdpwww.life.uiuc.edu/ ). The electronic mail and WWW servers provide ribosomal probe checking, approximate phylogenetic placement of user-submitted sequences, screening for possible chimeric rRNA sequences, automated alignment, and a suggested placement of an unknown sequence on an existing phylogenetic tree.

Animals↗
PubMed1999

Transcription Regulatory Regions Database (TRRD):its status in 1999.

The Transcription Regulatory Regions Database (TRRD) is a curated database designed for accumulation of experimental data on extended regulatory regions of eukaryotic genes, the regulatory elements they contain, i.e., transcription factor binding sites, promoters, enhancers, silencers, etc., and expression patterns of the genes. Release 4.1 of TRRD offers a number of significant improvements, in particular, a more detailed description of transcription factor binding sites, transcription factors per se, and gene expression patterns in a computer-readable format. In addition, the new TRRD release provides considerably more references to other molecular biological databases. TRRD 4.1 is installed under SRS and is available through the WWW at http://www.bionet.nsc.ru/trrd/

Animals↗
PubMed2006

LOCATE: a mouse protein subcellular localization database.

We present here LOCATE, a curated, web-accessible database that houses data describing the membrane organization and subcellular localization of proteins from the FANTOM3 Isoform Protein Sequence set. Membrane organization is predicted by the high-throughput, computational pipeline MemO. The subcellular locations of selected proteins from this set were determined by a high-throughput, immunofluorescence-based assay and by manually reviewing >1700 peer-reviewed publications. LOCATE represents the first effort to catalogue the experimentally verified subcellular location and membrane organization of mammalian proteins using a high-throughput approach and provides localization data for approximately 40% of the mouse proteome. It is available at http://locate.imb.uq.edu.au.

Animals↗
PubMed2002

Trends in long-term survival following liver resection for hepatic colorectal metastases.

OBJECTIVE: To examine trends in outcomes of patients undergoing resection at a single tertiary care referral center over a 16-year period. SUMMARY BACKGROUND DATA: Hepatic resection is considered the treatment of choice in selected patients with colorectal metastasis confined to the liver. Although a variety of retrospective studies have demonstrated improvements in short-term outcomes in recent years, changes in long-term survival over time are less well-established. METHODS: Data from 226 consecutive patients undergoing potentially curative liver resection for colorectal metastases between 1984 and 1999 were analyzed. Actuarial survival rates related to prognostic determinants were analyzed using the log-rank test. RESULTS: The median survival for the entire cohort was 46 months, with 5- and 10-year survival rates of 40% and 26% respectively. Ninety-three patients operated on between 1984 and 1992 were found to have an overall survival of 31% at 5 years, compared to 58% for the 133 patients operated on during the more recent period (1993-1999). Both overall and disease-free survival were significantly better in the recent time period compared with the earlier period on both univariate and multivariate analyses. Other independent factors associated with improved survival included number of metastatic tumors < or = 3, negative resection margin, and CEA < 100. Comparisons were made between time periods for a variety of patient, tumor and treatment-related factors. Among all parameters studied, only resection type (anatomical versus nonanatomical), use of intraoperative ultrasonography, and perioperative chemotherapy administration differed between the early and recent time periods. CONCLUSIONS: Long-term survival following liver resection for colorectal metastases has improved significantly in recent years at our institution. Although the reasons for this survival trend are not clear, contributing factors may include the use of newer preoperative and intraoperative imaging, increased use of chemotherapy, and salvage surgical therapy.

Adult↗
PubMed2003

Long-term outcome of extended hemihepatectomy for hilar bile duct cancer with no mortality and high survival rate.

OBJECTIVE: To demonstrate our strategy for hilar bile duct cancer and to elucidate prognostic factors and the surgeon's role in long-term survival. SUMMARY BACKGROUND DATA: Extended hemihepatectomy is recognized as a curative treatment of hilar bile duct cancer but is not always safe because of the risk of postoperative liver failure. A safe and beneficial strategy is required. METHODS: Fifty-eight consecutive major hepatectomies for hilar bile duct cancer were reviewed retrospectively. Appropriate preoperative treatments, biliary drainage, and portal embolization were performed before major hepatectomies. The short- and long-term results of our strategy are presented and analyzed. RESULTS: Biliary drainage and portal embolization were performed in 39 patients (67.2%) and 31 patients (53.4%), respectively. Major hepatectomies comprised 27 extended right and 22 extended left hemihepatectomies and 9 hepatoduodenopancreatectomies. Operative morbidity and mortality rates were 43% and 0%, respectively. There was no postoperative liver failure. The overall 5-year survival rate was 40%. Univariate analysis showed that residual tumor status, lymph node involvement, and perineural invasion were associated with patients' long-term survival. A surgical margin over 5 mm resulted in better long-term survival. The delay resulting from preoperative treatment was not detrimental to long-term survival. Multivariate analysis showed that lymph node involvement was the only prognostic factor. CONCLUSIONS: Our strategy, which includes preoperative biliary drainage and portal embolization, led to a reduction in the risks associated with major hepatectomy for hilar bile duct cancer, and resulted in zero mortality. Surgeons should aim at complete clearance of the tumor with an adequate surgical margin to ensure optimal long-term survival.

Adult↗
PubMed2005

Prediction of recurrence after radical surgery for gastric cancer: a scoring system obtained from a prospective multicenter study.

OBJECTIVE: The aim of this prospective multicenter study was to define a scoring system for the prediction of tumor recurrence after potentially curative surgery for gastric cancer. SUMMARY BACKGROUND DATA: The estimation of the risk of recurrence in individual patient may be relevant in clinical practice, to apply adjuvant therapies after surgery, and plan an adequate follow-up program. Only a few studies, most of which were retrospective or performed on a limited number of patients, have developed a prognostic score in patients with gastric cancer. METHODS: A total of 536 patients who underwent UICC R0 resection between 1988 and 1998 at 3 surgical departments in Italy were considered. All patients were followed up using a standard protocol after discharge from the hospital. The mean follow-up period was 56 +/- 44 months, and 94 +/- 29 months for surviving patients. The scoring system was calculated on the basis of a logistic regression model, where the presence of the recurrence was the dependent variable, and clinicopathologic variables were the covariates. RESULTS: Recurrence occurred in 272 of 536 patients (50.7%). The scoring system for the prediction of the risk in individual cases gave values ranging from 1.4 to 99.9; the model distributed most cases in the extremes of the range. The risk of recurrence increased remarkably with score values; it was only 5% in patients with a score below 10, up to 95.4% in patients with a score of 91 to 100. No recurrence was observed in 43 patients with a score below 4, whereas all of the 56 patients with a score over 97 presented a recurrence. The model correctly predicted recurrence in 227 of 272 patients (sensitivity, 83.5%), whereas the absence of recurrence was correctly predicted in 214 of 264 patients (specificity, 81.1%); the overall accuracy was 82.2%. Prognostic score was clearly superior to UICC tumor stage in predicting recurrence. The high effectiveness of the score was confirmed in preliminary data of a validation study. CONCLUSIONS: The scoring system obtained with a regression model on the basis of our follow-up data is useful for defining subgroups of patients at a very low or very high risk of tumor recurrence after radical surgery for gastric cancer. Final results of the validation study are essential for a clinical application of the model.

Adult↗
PubMed2005

Patients' refusal of surgery strongly impairs breast cancer survival.

OBJECTIVE: To compare patient and tumor characteristics and survival between women who refused and women who accepted surgery for breast cancer. SUMMARY BACKGROUND DATA: Surgery represents the central component of curative breast cancer treatment, but some women decide not to undergo surgery. Recent studies on the prognosis of non operated breast cancer are nonexistent. PATIENTS AND METHODS: This study included all 5339 patients aged < 80 years with nonmetastatic breast cancer recorded at the Geneva Cancer Registry between 1975 and 2000. We consulted the clinical files of all nonoperated women to identify those who refused surgery. Patients who refused surgery were compared with those accepting surgery using logistic regression. The effect of refusal of surgery on breast cancer mortality was evaluated by Cox proportional hazards analysis. RESULTS: Seventy patients (1.3%) refused surgery. These women were older, more frequently single, and had larger tumors. Overall, 37 (53%) women had no treatment, 25 (36%) hormone-therapy alone, and 8 (11%) other adjuvant treatments alone or in combination. Five-year specific breast cancer survival of women who refused surgery was lower than that of those who accepted (72%, 95% confidence interval, 60%-84% versus 87%, 95% confidence interval, 86%-88%, respectively). After accounting for other prognostic factors including tumor characteristics and stage, women who refused surgery had a 2.1-fold (95% confidence interval, 1.5-3.1) increased risk to die of breast cancer compared with operated women. CONCLUSIONS: Women who refuse surgery for breast cancer have a strongly impaired survival. This information might help patients who are hesitant toward surgery make a better informed decision.

Aged↗
PubMed2005

Normal and modified urinary nucleosides represent novel biomarkers for colorectal cancer diagnosis and surgery monitoring.

BACKGROUND: Up to now, there is still no ideal tumor marker in early diagnosis and effective monitoring, especially for surgical resection of colorectal cancer (CRC). The aim of the present study was to evaluate the application of urinary normal and modified nucleosides in diagnosis and surgery monitoring of CRC. METHODS: Between October 2002 and July 2003, 52 consecutive patients with pathological confirmed CRC were enrolled. Spontaneous urine samples were collected 1 day before surgery and on day 8 postoperatively, and 14 urinary nucleosides were determined by reverse-phase high-performance liquid chromatography (RP-HPLC). Another 62 healthy people were also studied as control. The clinical routine tumor markers, serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA)199, CA125, and alpha-fetoprotein (AFP) of CRC patients, were correspondingly evaluated by electrochemiluminescent immunoassay. RESULTS: The levels of 11 out of 14 of the determined urinary nucleosides in the CRC group were much higher than those of normal controls. Through the principal component analysis of these 14 nucleosides, 76.9% of CRC patients were correctly classified. The sensitivity of this analysis was much higher than that of CEA (38.5%), CA199 (40.4%), CA125 (15.4%), and AFP (17.3%; P < 0.01). Receiver operating characteristic (ROC) curve analysis of 1-methylguanosine (m1G) and pseudouridine (Pseu) showed good sensitivity-specificity profiles of the diagnosis of CRC. The elevated levels of the nine nucleosides significantly decreased after curative resection of 40 CRC cases. The data also showed that the preoperative levels of some nucleosides were positively related with tumor size and Dukes staging of CRC. CONCLUSION: The evaluation of normal and modified urinary nucleosides might become novel tumor markers, which will be facilitated in the clinical setting and helpful in the diagnosis, management and follow up of CRC. Pseu and m1G may be more promising for clinical use and be worthy of further studies in the near future.

Adult↗
PubMed2003

Database for renal collecting duct regulatory and transporter proteins.

The mammalian kidney collecting duct plays an important role in the fine regulation of Na, K, water, and acid-base balance. Functional genomic and proteomic studies of the kidney offer new opportunities in the understanding of renal physiology and pathophysiology, and the collecting duct is an appropriate target tissue because of the relative simplicity of its cells and the ease of isolating or culturing large numbers of collecting duct cells. Study of the collecting duct includes assessment of gene expression and protein regulation and abundance. For example, DNA and protein microarrays can be used to quantitate gene expression and protein regulation and abundance under varying physiological conditions. An Internet-accessible database has been devised for major collecting duct proteins involved in transport and regulation of cellular processes. The individual proteins included in this database are those culled from literature searches and from previously published studies involving cDNA arrays and serial analysis of gene expression (SAGE). Design of microarray targets for the study of kidney collecting duct tissues is facilitated by the database, which includes links to curated base pair and amino acid sequence data, relevant literature, and related databases. Use of the database is illustrated by a search for water channel proteins, aquaporins, and by a subsequent search for vasopressin receptors. Links are shown to the literature and to sequence data for human, rat, and mouse, as well as to relevant web-based resources. Extension of the database is dynamic and is done through a maintenance interface. This permits creation of new categories, updating of existing entries, and addition of new ones.

Animals↗
PubMed2001

Laser cordotomy versus radiotherapy: an objective cost analysis.

This study presents a cost analysis of and comparison between laser cordotomy and external beam irradiation for the treatment of early glottic carcinoma. It compares the curative results of the two modalities from data of a retrospective study at my institution and a literature review of published cure rates. It also reviews the results of objective voice assessments in cases representing both treatments. The findings of this study indicate that the cure rates are equivalent and that voice quality obtained after laser cordotomy is comparable to that obtained after irradiation, yet the total cost of external beam radiotherapy is significantly higher than that of laser surgery. Hence, the findings of this study provide strong support for initially treating early glottic tumors with laser surgery.

Adult↗
PubMed2005

The development of common data elements for a multi-institute prostate cancer tissue bank: the Cooperative Prostate Cancer Tissue Resource (CPCTR) experience.

BACKGROUND: The Cooperative Prostate Cancer Tissue Resource (CPCTR) is a consortium of four geographically dispersed institutions that are funded by the U.S. National Cancer Institute (NCI) to provide clinically annotated prostate cancer tissue samples to researchers. To facilitate this effort, it was critical to arrive at agreed upon common data elements (CDEs) that could be used to collect demographic, pathologic, treatment and clinical outcome data. METHODS: The CPCTR investigators convened a CDE curation subcommittee to develop and implement CDEs for the annotation of collected prostate tissues. The draft CDEs were refined and progressively annotated to make them ISO 11179 compliant. The CDEs were implemented in the CPCTR database and tested using software query tools developed by the investigators. RESULTS: By collaborative consensus the CPCTR CDE subcommittee developed 145 data elements to annotate the tissue samples collected. These included for each case: 1) demographic data, 2) clinical history, 3) pathology specimen level elements to describe the staging, grading and other characteristics of individual surgical pathology cases, 4) tissue block level annotation critical to managing a virtual inventory of cases and facilitating case selection, and 5) clinical outcome data including treatment, recurrence and vital status. These elements have been used successfully to respond to over 60 requests by end-users for tissue, including paraffin blocks from cases with 5 to 10 years of follow up, tissue microarrays (TMAs), as well as frozen tissue collected prospectively for genomic profiling and genetic studies. The CPCTR CDEs have been fully implemented in two major tissue banks and have been shared with dozens of other tissue banking efforts. CONCLUSION: The freely available CDEs developed by the CPCTR are robust, based on "best practices" for tissue resources, and are ISO 11179 compliant. The process for CDE development described in this manuscript provides a framework model for other organ sites and has been used as a model for breast and melanoma tissue banking efforts.

Computational Biology↗
PubMed1981

Effect of diisopropyl 1,3-dithiol-2-ylidenemalonate (NKK-105) on fatty liver induced by carbon tetrachloride.

The therapeutic effect of diisopropyl 1,3-dithiol-2-ylidenemalonate (NKK-105) on the fatty liver induced by carbon tetrachloride (CCl4) was studied. The recovery from elevated liver triglyceride levels induced by CCl4 required over 20 days in 35 week-old rats, but 14 days in 6 week-old rats. This indicates that 35 week-old rats are useful for studying the therapeutic effect of NKK-105 on fatty liver. In rats with CCl4-induced fatty liver, NKK-105 lowered the hepatic triglyceride level, accelerated the rate of triglyceride release from the liver, enhanced the incorporation of 14C-leucine into microsomal protein, and increased the RNA content in microsomes. These data suggest that NKK-105 exerts a curative effect on CCl4-induced fatty liver by improving the impaired protein synthesis and by promoting lipoprotein secretion.

Animals↗