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PubMedDate not supplied

The evolving role of proteomics in the early detection of breast cancer.

There has been emerging interest in the examination of tumor protein expression (proteomics) as a means to identify novel diagnostic and therapeutic targets in women with breast cancer. Specifically, several investigators have examined biological fluids (serum and breast ductal fluid) and breast tissue in an attempt to detect novel proteomic profiles in women with breast carcinoma. The current tools of proteomic research are evolving, but include two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. Initial studies have identified several unique biomarkers and proteomic profiles that were able to discriminate between non-cancer and breast cancer patients. In the future, the application of large-scale proteomic technology may provide a means of early detection, surveillance, and identification of potential therapeutic targets.

Biomarkers, Tumor↗
PubMed1991

A proton gradient is required for the transport of two lumenal oxygen-evolving proteins across the thylakoid membrane.

The 33- and 23-kDa proteins of the photosynthetic oxygen-evolving complex are synthesized in the cytosol as larger precursors and transported into the thylakoid lumen via stromal intermediate forms. We have investigated the energetics of protein transport across the thylakoid membrane using import assays that utilize either intact chloroplasts or isolated thylakoids. We have found that the light-driven import of the 23-kDa protein into isolated thylakoids is almost completely inhibited by electron transport inhibitors or by the ionophore nigericin but not by valinomycin. These compounds have similar effects in chloroplast import assays: precursors of both the 33- and 23-kDa proteins are imported and processed to intermediate forms in the stroma, but transport into the thylakoid lumen is blocked when electron transport is inhibited or nigericin is present. These results indicate that the transport of these proteins across the thylakoid membrane requires a protonmotive force and that the dominant component in this respect is the proton gradient and not the electrical potential.

Biological Transport↗
PubMed2006

Outpatient treatment of community-acquired pneumonia: evolving trends and a focus on fluoroquinolones.

BACKGROUND: Increasing use of broad-spectrum antibiotics in the community, including fluoroquinolones, has been reported, despite concerns for developing antibiotic resistant organisms. Community-acquired pneumonia (CAP) is commonly treated on an outpatient basis, and recent treatment guidelines suggest only a limited role for fluoroquinolones. OBJECTIVES: To identify evolving trends in the outpatient treatment of CAP in adults, and to identify factors associated with receipt of a fluoroquinolone. METHODS: Retrospective observational design using population-based administrative data. Initial outpatient treatment for subjects diagnosed with CAP between May 1996 and March 2002 was examined. Logistic regression was used to examine the influence of patient characteristics on the receipt of a fluoroquinolone. RESULTS: A total of 31,940 outpatients with CAP were identified. The proportion of patients receiving fluoroquinolones increased from 6.6% in 1996/97 to 25.2% in 2001/02. Over the course of the study, 158 (25.9%) of the 610 patients meeting the eligibility criteria for treatment with fluoroquinolones, according to treatment guidelines, received these agents. Of the 31,330 subjects who did not meet the eligibility criterion, 3,886 (12.4%) received a fluoroquinolone. Other variables that influenced the receipt of a fluoroquinolone included: age (for every 10-year increase) [OR=1.16 (1.14-1.19)], urban residence [OR=1.40 (1.30-1.51)], presentation to an emergency department [OR=0.80 (0.70-0.90)], high-level drug use (six or more different drugs in the previous year) [OR=1.50 (1.41-1.59)], and income-level (highest to lowest) [OR=1.20 (1.08-1.35)]. CONCLUSION: The use of fluoroquinolones for the treatment of CAP is increasing. However less than 4% of the subjects receiving fluoroquinolones met eligibility requirements according to treatment guidelines. Initiatives to increase the uptake of treatment guidelines appear warranted.

Adolescent↗
PubMed2006

Gene clusters for beta-lactam antibiotics and control of their expression: why have clusters evolved, and from where did they originate?

While beta-lactam compounds were discovered in filamentous fungi, actinomycetes and gram-negative bacteria are also known to produce different types of beta-lactams. All beta-lactam compounds contain a four-membered beta-lactam ring. The structure of their second ring allows these compounds to be classified into penicillins, cephalosporins, clavams, carbapenens or monobactams. Most beta-lactams inhibits bacterial cell wall biosynthesis but others behave as beta-lactamase inhibitors (e.g., clavulanic acid) and even as antifungal agents (e.g., some clavams). Due to the nature of the second ring in beta-lactam molecules, the precursors and biosynthetic pathways of clavams, carbapenems and monobactams differ from those of penicillins and cephalosporins. These last two groups, including cephamycins and cephabacins, are formed from three precursor amino acids that are linked into the alpha-aminoadipyl-L-cysteinyl-D-valine tripeptide. The first two steps of their biosynthetic pathways are common. The intermediates of these pathways, the characteristics of the enzymes involved, the lack of introns in the genes and bioinformatic analysis suggest that all of them should have evolved from an ancestral gene cluster of bacterial origin, which was surely transferred horizontally in the soil from producer to non-producer microorganisms. The receptor strains acquired fragments of the original bacterial cluster and occasionally inserted new genes into the clusters, which once modified, acquired new functions and gave rise to the final compounds that we know. When the order of genes in the Streptomyces genome is analyzed, the antibiotic gene clusters are highlighted as gene islands in the genome. Nonetheless, the assemblage of the ancestral beta-lactam gene cluster remains a matter of speculation.

Anti-Bacterial Agents↗
PubMed1991

Every enhancer works with every promoter for all the combinations tested: could new regulatory pathways evolve by enhancer shuffling?

The promoters and enhancers of cell type-specific genes are often conserved in evolution, and hence one might expect that a given enhancer has evolved to work best with its own promoter. While this expectation may be realized in some cases, we have not found evidence for it. A total of 27 combinations of different promoters and enhancers were tested by transfection into cultured cells. We found that the relative efficiency of the enhancers is approximately the same, irrespective of the type of promoter used, i.e., there was no strong preference for any given enhancer/promoter combination. Notably, we do not see particularly strong transcription when the immunoglobulin kappa enhancer (or the immunoglobulin heavy chain enhancer) is used to activate a kappa gene promoter. We propose that a generally permissive enhancer/promoter interaction is of evolutionary benefit for higher eukaryotes: by enhancer shuffling, genes could be easily brought under a new type of inducibility/cell type specificity.

B-Lymphocytes↗
PubMed2004

A nation's genes for a cure to cancer: evolving ethical, social and legal issues regarding population genetic databases.

The advent of the human genome sequence has focused research on understanding underlying genetic links to complex diseases such as cancer, asthma and heart disease. In the past few years, individual countries, such as Iceland, Estonia, Singapore and the United Kingdom, have created national databases of their citizens' DNA for comparative research. Most recently, an international consortium including Nigeria, Japan, China and the United States launched a $100 million project called the International HapMap to map the human genome according to haplotypes, blocks of DNA that contain genetic variation. Such population genetic databases present challenging ethical, social and legal issues, yet regulation of genetic information has developed sporadically, from region to region, without a consistent international standard. Without a clear understanding of the consequences of genetic research in terms of individual and community-wide discrimination and stigmatization, genetic databases raise concerns about the protection of genetic information. This Note provides a survey of the evolving landscape of population genetic databases as a legislative and public policy tool for national and international regulators. It compares different approaches to regulating the collection and use of population genetic databases in order to understand what areas of consensus are formulating a foundation for an international standard. As the first population genetics project that will span multiple countries for the collection of DNA, the International HapMap has the potential to become an influential standard for the protection of population genetic information. This Note highlights issues among the national databases and the HapMap project that raise ethical, social and legal concerns for the future and recommends further protections for both individual donors and community interests.

Access to Information↗
PubMed2006

Surgical fixation of pathologic fractures: an evaluation of evolving treatment methods.

The surgical techniques for the fixation of pathologic fractures continue to evolve. The present study examines clinical outcomes and complications associated with the use of newer generation interlocked intramedullary nails compared with open reduction and internal fixation with plates and screws for pathologic fractures in long bones. Fifty operative procedures performed on 37 patients by five community orthopaedic surgeons were retrospectively reviewed. The operative procedures were separated into two groups based upon the method of fracture fixation; the groups were compared for differences in hardware or fixation failure. The use of intramedullary devices was associated with a significantly lower number of hardware or fixation failures (p < 0.02). This data, in addition to several additional advantages of indirect reduction and intramedullary fixation of pathologic fractures, supports this method of fracture care over open reduction and internal fixation in appropriate cases.

Adult↗
PubMed2006

Evolving with Medicare: an approach to retirement strategy.

With Medicare Part D now providing prescription drug coverage, employers' retiree health plans are ripe for change. Effective change requires more than just adjustments. A global or enterprisewide approach to the development of a retirement strategy is important and should encompass five components: design, finance, administration, communication and control. This article discusses the strategic approach to crafting retiree health policy as the Medicare landscape continues to evolve.

Health Benefit Plans, Employee↗
PubMed2006

The evolving management of Burkitt's lymphoma at Red Cross Children's Hospital.

BACKGROUND: Treatment for Burkitt's lymphoma at Red Cross Children's Hospital has evolved from the use of aggressive surgery and less intensive chemotherapy to a conservative surgical approach with more intensive chemotherapy. METHODS: The study was a retrospective folder review of patients diagnosed with Burkitt's lymphoma at RCCH between 1984 and 2004. RESULTS: Ninety-two children were treated for Burkitt's lymphoma at RCCH between 1984 and 2004. There were 10 patients with group A or fully resected disease, 52 with group B or extensive localised disease, and 30 with dissemination to the bone marrow and/or central nervous system or group C disease. Protocol 1 (less intensive chemotherapy based on the COMP regimen) was used from 1984, with protocol 2 (more intensive chemotherapy based on the LMB regimen) introduced in 1988 for group C disease, 1991 for group B disease and 1996 for group A disease. Overall 5-year survival increased from 20% with protocol 1 to 66% with protocol 2 for group C disease, and from 76.5% with protocol 1 to 88.2% with protocol 2 for group B disease. There were more admissions for neutropenic fever in patients on protocol 2 and more episodes of mucositis, and these patients required more red cell and platelet transfusions. With a more conservative surgical approach, biopsy largely replaced attempts to partially resect the tumour at primary surgery, and there was a consequent decline in surgical complications. CONCLUSIONS: Intensive chemotherapy with protocol 2 has resulted in improved survival for group C and group B patients, but with more morbidity. Protocol 1, which is less intensive with less morbidity, remains a viable strategy for group A and group B disease in resource-poor settings.

Adolescent↗
PubMed2006

[The history of evolvement of bronchoscope].

Since 1897, the year when the bronchoscope was invented, the instrument have experienced three stages of evolvement, namely, the period of conventional rigid bronchoscope, the period of flexible fibreoptic bronchoscope as well as the period of the combined use of electronic bronchoscope, broncho fibrescope and video-assisted rigid bronchoscope simultaneously. Bronchoscope plays a significant role in the fields of thoracic surgery and respiratory internal medicine. In China, the technique started rather late, but after years of hard work, it has approached or reached the international advanced level. The blossoming new techniques and their upgrading make bronchoscope play an even more important role in the interventional pulmonology.

Bronchoscopes↗
PubMed1991

[Prolonged erythrocytic T activation, depression of blood group A and increase of fetal hemoglobin in a myelodysplastic syndrome evolving into erythroleukemia].

T cryptantigen can be exposed on the red cell membrane as a result of removal of terminal glycosides, either by bacterial enzymes or by incomplete synthesis of the cell membrane due to somatic mutation, usually caused by a neoplasm. T-activated erythrocytes have been observed in different pathologies, but they have not been seen associated with other abnormalities of red blood cell proteins described in myelodysplastic syndromes or acute leukaemias. A patient with initial diagnosis of refractory anaemia that evolved into erythroleukaemia showed prolonged T-activation, a depressed A blood-group antigen and an increase of foetal haemoglobin, simultaneously. The evolutive pattern of T-activation suggests more an abnormal erythropoiesis than an enzymatic effect and a certain relationship with the haemolytic syndrome.

ABO Blood-Group System↗
PubMed1991

Hypereosinophilic syndrome evolving to acute lymphoblastic leukemia.

We report a case of hypereosinophilic syndrome (HES) which later evolved into acute lymphoblastic leukemia (ALL). A 37-year-old man showed typical clinical manifestations of HES: pulmonary infiltrates, erythematous skin rash, deep vein thrombosis, endomyocardial fibrosis, and diffuse central nervous system dysfunctions. Although he was treated with prednisolone and hydroxyurea, marked eosinophilia persisted and lymphoblasts gradually increased in the bone marrow. He died of severe disseminated fungal infection after anti-leukemic therapy. Autopsy revealed marked fibrous thickening of the endocardium, bilateral common iliac vein thrombosis, and chronic hepatitis with fibrosis. Neither eosinophilic nor leukemic cell infiltration was seen in any tissue at autopsy. Including this case, 24 patients with ALL and hypereosinophilia have been reported in English-language literature. We discuss the relationship between eosinophilia and ALL, and the mechanisms, particularly the role of eosinophil cationic protein (ECP), in causing various organ system dysfunctions in HES.

Adult↗
PubMed1991

[A case of disproportionately large communicating fourth ventricle after resection of temporal astrocytoma that evolved an isolated fourth ventricle].

The isolation and enlargement of the fourth ventricle after a ventriculoperitoneal (V-P) shunt was classified as "isolated fourth ventricle (IFV)". The term, "disproportionately large communicating fourth ventricle (DFV)" was first introduced by Scotti et al as being an enlarged fourth ventricle communicating with the third ventricle. The authors present a case of DFV after the resection of an astrocytoma. Upon recurrence of the tumor a second resection was carried out 5 years later. It was found that IFV had evolved because a cyst in the right temporal lobe was obstructing the aqueduct. After shunting of the tumor cyst, the aqueduct was again found to be patent and the fourth ventricle gradually decreased in size. A 34-year-old female presented headache, nausea, and a mild left hemiparesis. An initial CT scan demonstrated a fourth ventricle of approximately normal size and a right temporal mass. The first craniotomy revealed an astrocytoma. A CT scan after the surgical procedure showed enlargement of all ventricles, especially the fourth, resulting from the blockage of the foramina of Luschka and Magendie. The insertion of a V-P shunt was followed by a reduction in size of all ventricles. The diagnosis of DFV was thus confirmed because the fourth ventricle had a demonstrated communication with the third ventricle. After a second craniotomy for tumor recurrence five years later, a CT scan revealed the enlargement of the fourth ventricle and a cyst in the right temporal lobe. A metrizamide CT scan revealed that the cyst was isolated and an RI ventriculogram confirmed obstruction of the aqueduct.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Evolving concepts of molar pregnancy.

Molar pregnancy is composed of two distinct clinical and pathologic entities, complete and partial mole. Knowledge of the cytogenetic origin, natural history and treatment of complete and partial hydatidiform mole is evolving.

Chorionic Gonadotropin↗
PubMed1991

The development of the Laryngeal Mask--a brief history of the invention, early clinical studies and experimental work from which the Laryngeal Mask evolved.

The history of the invention and development of the Laryngeal Mask in the East End of London during the years 1981-88 is briefly described. The concept evolved from home-made prototypes built from the Goldman Dental Mask through a complex series of one-off latex models culminating in a primitive factory-made silicone cuff in 1986. This work defined the design parameters necessary to reconcile the needs for safety, reliability and ease of insertion while at the same time exploring the limits to possible use. In early 1988 the final version was tested by the inventor who had by this time used the device in more than 7500 patients undergoing routine surgery. From this experience a number of important lessons were learned relating to safe and effective use, which are summarized in the inventor's Instruction Manual. The importance of referring to this volume before use is stressed.

Anesthesiology↗
PubMed1991

Transport of proteins into chloroplasts. Requirements for the efficient import of two lumenal oxygen-evolving complex proteins into isolated thylakoids.

The 33- and 23-kDa proteins of the photosynthetic oxygen-evolving complex are synthesized in the cytosol and targeted into the thylakoid lumen by bipartite presequences. In this report, we describe conditions for the efficient import of each of these proteins by isolated pea thylakoids. Import of the 33-kDa protein requires both light and stromal extract. The probable function of the stromal extract is to provide stromal processing peptidase to remove the first "envelope transit" signal of the presequence. Import of the 23-kDa protein is also driven by light, but stromal extract is not required for import; furthermore, efficient import is still observed if the precursor is modified to completely block cleavage by residual stromal processing peptidase activity. The intermediate form of the 23-kDa protein, which is generated by incubation of the precursor protein with stromal processing peptidase, is also efficiently imported. The results indicate that the thylakoidal protein transport system can import both the precursor and intermediate forms of the 23-kDa protein, but probably only the intermediate form of the 33-kDa protein.

Adenosine Triphosphate↗
PubMedDate not supplied

Conflict resolution strategies: when ethical dilemmas evolve into conflict.

In critical care, ethical dilemmas arise when all duties, rights, and goals cannot be satisfied by the alternatives that are available. Conflicts evolve from ethical dilemmas due to differences in how nurses, physicians, administrators, and patients or families who are involved in a clinical situation assign priorities or interpret roles and responsibilities. This author presents strategies for critical care nurses to use to resolve conflicts that arise in relation to ethical dilemmas.

Conflict, Psychological↗
PubMed1991

Heavy chain variable region gene families evolved early in phylogeny. Ig complexity in fish.

The V regions of channel catfish H chain cDNA clones have been analyzed. Based upon sequence relationships and hybridization analyses, five different groups of VH genes are identified whose definition is consistent with that of five different VH families. Genomic Southern blots indicate that as many as 100 different germ-line VH genes are likely represented by these families. The sequence diversity between identified members of these different families is similar in magnitude to the divergence represented between members of different human or mouse VH families. The FR regions are the most conserved regions when members of different catfish VH families are compared; specific amino acid positions appear to be highly conserved in phylogeny. Equally important is that diversity is represented in complementarity-determining regions CDR1 and CDR2 in members of the different families as well as in members of the same VH family. These results suggest that an extensive repertoire of VH genes can contribute to antibody diversity in this lower vertebrate. Sequence comparisons indicate that one of the catfish VH families shares considerable structural similarity to several higher vertebrate VH gene families--a relationship which suggests that this VH family may be ancestral to some VH gene families of higher vertebrates. Characteristic of the genomic organization of higher vertebrate H chains, catfish appear to have different VH families wherein a VH gene likely undergoes functional recombination with putative DH gene segments and one of apparently several different JH segments. The recombined V region is expressed with the same C region gene. These combined results suggest that bony fishes are the earliest known phylogenetic representatives to have evolved extensive V region gene families.

Animals↗