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PubMed2002

The evolving role of monoclonal antibodies and dendritic cell therapy in hematologic malignancies.

The approach for treatment of hematological cancers had changed in the last decade from non-specific eradication of tumor cells by chemotherapy to more specific strategies by activation of immune system. There are number of potential targets of immune responses in patients with hematological malignancies. Some have been developed like monoclonal antibody therapy and others that have yet to be define like dendritic cell infusion. In this review, we will discuss the evolving role of monoclonal antibody therapy and donor dendritic cell infusion in mounting on immune response in hematological malignancies.

Antibodies, Monoclonal↗
PubMed2005

First real-time measurement of the evolving 2H/1H ratio during water evaporation from plant leaves.

We have studied the temporal behaviour of the deuterium isotope ratio of water vapour emerging from a freshly cut plant leaf placed in a dry nitrogen atmosphere. The leaf material was placed directly inside the sample gas cell of the stable isotope ratio infrared spectrometer. At the reduced pressure ( approximately 40 mbar) inside the cell, the appearance of water evaporating from the leaf is easily probed by the spectrometer, as well as the evolving isotope ratios, with a precision of about 1 per thousand. The demonstration experiment we describe measures the 2H/1H isotope ratio only, but the experiment can be easily extended to include the 18O/16O and 17O/16O isotope ratios. Plant leaf water isotope ratios provide important information towards quantification of the different components in the ecosystem water and carbon dioxide exchange.

Carbon Dioxide↗
PubMed2026

Complicated urinary tract infections: evolving definitions, clinical burden, and treatment landscape amid antimicrobial resistance.

INTRODUCTION: Complicated urinary tract infection (cUTI) is a common and heterogeneous infection associated with substantial morbidity, high healthcare utilization, and increasing antimicrobial resistance. Evolving definitions, increasing device use, and changing patient populations have altered its epidemiology and management. Marked variability in diagnostic criteria, clinical trial endpoints within and outside registrational settings, and treatment strategies complicates clinical decision-making and interpretation of therapeutic advances. AREAS COVERED: This review examines contemporary cUTI epidemiology, classification frameworks, and drivers of disease burden. It evaluates resistance trends and their therapeutic implications, alongside stewardship-based management strategies, including empiric antibiotic selection, intravenous-to-oral transition, treatment duration, and source control. Challenges in catheter-associated infection, recurrence, and regulatory endpoint design are discussed, together with the emerging role of novel agents targeting resistant Gram-negative pathogens. EXPERT OPINION: Rising multidrug resistance and limited oral options are reshaping cUTI management, necessitating individualized, stewardship-aligned therapy guided by illness severity and local epidemiology. Current regulatory endpoints inadequately reflect patient-centered outcomes, particularly in the context of asymptomatic bacteriuria. Expanding availability of effective oral agents may enable earlier discharge and outpatient care. Integration of rapid diagnostics and risk stratification will be essential to optimize therapy, limit resistance, and improve outcomes.

Humans↗
PubMedDate not supplied

The evolving definition of a chondrodysplasia?

Most individuals who deal with chondrodysplasias would agree that this term refers collectively to a genetically and clinically heterogeneous group of disorders of skeletal development and growth. But they might not agree on what constitutes a specific chondrodysplasia. Indeed, the way in which a specific chondrodysplasia is defined has evolved substantially over the past several decades. David Rimoin, to whom this special issue is dedicated, has played a vital role in this evolution.

Humans↗
PubMed2003

A patient with classical polyarteritis nodosa evolving into end stage renal failure.

Classical polyarteritis nodosa (c-PAN) is a form of systemic necrotizing vasculitis mainly affecting medium-size arteries, is not associated with renal glomerular disease and acute renal failure. Perirenal hematoma can be seen in up to fifty percent of c-PAN patients and minority of them develop mild renal impairment. Herein, we describe a 34-year-old male with c-PAN who presented with rapidly progressive renal failure and evolved into end stage renal disease.

Acute Kidney Injury↗
PubMed1991

Physiologically active chloroplasts contain pools of unassembled extrinsic proteins of the photosynthetic oxygen-evolving enzyme complex in the thylakoid lumen.

The oxygen-evolving complex (OEC) of photosystem II (PS II) consists of at least three extrinsic membrane-associated protein subunits, OE33, OE23, and OE17, with associated Mn2+, Ca2+, and Cl- ions. These subunits are bound to the lumen side of PS II core proteins embedded in the thylakoid membrane. Our experiments reveal that a significant fraction of each subunit is normally present in unassembled pools within the thylakoid lumen. This conclusion was supported by immunological detection of free subunits after freshly isolated pea thylakoids were fractionated with low levels of Triton X-100. Plastocyanin, a soluble lumen protein, was completely released from the lumen by 0.04% Triton X-100. This gentle detergent treatment also caused the release from the thylakoids of between 10 and 20%, 40 and 60%, and 15 and 50% of OE33, OE23, and OE17, respectively. Measurements of the rates of oxygen evolution from Triton-treated thylakoids, both in the presence and absence of Ca2+, and before and after incubation with hydroquinone, demonstrated that the OEC was not dissociated by the detergent treatment. Thylakoids isolated from spinach released similar amounts of extrinsic proteins after Triton treatment. These data demonstrate that physiologically active chloroplasts contain significant pools of unassembled extrinsic OEC polypeptide subunits free in the lumen of the thylakoids.

Calcium↗
PubMed1981

Qa-2, H-2K, and H-2D alloantigens evolved from a common ancestral gene.

The Tla region located on the murine 17th chromosome controls several serologically defined cell surface antigens. These antigens, referred to as Qa-1-5 and TL, are expressed on a variety of hematopoeitic cell populations. In the present studies we have immunoprecipitated isotopically labeled Qa-2 and H-2 molecules from mitogen-stimulated B6 spleen cells. Sequential immunoprecipitation experiments have shown that the determinants recognized by alpha Qa-2, alpha H-2Kb, and alpha H-2Db alloantisera reside on separate molecular species. Comparative mapping of the arginine-labeled tryptic peptides from Qa-2, H-2Kb, and H-2Db molecules indicate that Qa-2 is structurally distinct but that there is considerable structural homology; 21-43% of the Qa-2 peptides co-chromatograph with peptides derived from H-2Db and H-2Kb, respectively. Similar levels of homology are observed when Qa-2 is compared with H-2Kk or H-2Dd. The results show that the Qa-2 alloantigen is encoded by a locus separate from the loci encoding H-2K or H-2D alloantigens, but that the Qa-2, H-2K, and H-2D alloantigens are sufficiently related at the primary structural level to indicate that they evolved from a common primordial gene.

Amino Acid Sequence↗
PubMed1998

Rapidly evolving hepatitis C virus-related cirrhosis in a human immunodeficiency virus-infected patient receiving triple antiretroviral therapy.

Triple antiretroviral therapy combining reverse transcriptase and protease inhibitors modifies the prognosis of human immunodeficiency virus (HIV) infection, with dramatic improvement in immune status. The precise impact, if any, of anti-HIV triple therapy on hepatitis C virus (HCV) infection is unknown. We describe an unusual case of rapidly evolving HCV-related cirrhosis that paralleled restoration of immune status in an HIV-infected patient and discuss the possible link between such a severe course of hepatitis C and anti-HIV triple therapy.

Adult↗
PubMed2003

Forty years on: how radiological protection has evolved internationally.

In the 40 years since the Society for Radiological Protection (SRP) was founded, the international scene has changed considerably. The United Nations bodies primarily involved, the United Nations Scientific Committee on the Effects of Atomic Radiation and the International Atomic Energy Agency, have evolved from fledgling organisations to indispensable major resources. A similar development characterises regional entities such as Euratom and the OECD Nuclear Energy Agency. The International Commission on Radiological Protection (ICRP), once interested in occupational health in the practice of medicine only, has shifted its emphasis towards protection of members of the public and of patients exposed to ionising radiations and is currently looking at protection of non-human species. The International Radiation Protection Association, the federation that is now the 'mother society' of the SRP, had not even been launched formally when the SRP started. At that time, non-ionising radiation was on nobody's mind, and the forerunner of today's International Commission on Non-Ionizing Radiation Protection (ICNIRP) was not formed until 1977. Basically, the developments during this period must be described as a great success story. Average occupational exposures to ionising radiation have decreased markedly, the number of accidents is small, almost all countries now regulate exposures roughly in line with ICRP and ICNIRP recommendations, and quite a large number of countries also have reasonable regulatory infrastructures. An area where problems appear to be on the increase, perhaps in part because of increasing awareness, concerns 'orphan sources' and lack of source security. This may indicate a need for closer attention to security outside the nuclear fuel cycle, e.g. in hospitals and non-nuclear industry.

Cost-Benefit Analysis↗
PubMed2004

The need for economic evaluation of telemedicine to evolve: the experience in Alberta, Canada.

Economic evaluation of telemedicine applications is required to provide decision makers in health care with appropriate information on costs and benefits of this information and communications technology. The level of economic evaluation should evolve as telemedicine applications mature. At the basic level, economic evaluation may include basic cost analysis and primarily observational data on nonmonetary benefits. The focus will change as telemedicine programs develop. At this intermediate level, practice patterns and workforce issues are addressed as they affect utilization and costs of telemedicine services. Longer-term economic evaluation, thus far not achieved in telemedicine assessment, should focus on assessment of health outcomes and economic impact. Alberta, Canada has made progress assessing telemedicine applications in psychiatry, radiology, rheumatology, and rehabilitation. Data availability and analytic resources continue to present challenges to economic assessment of telemedicine.

Alberta↗
PubMed2005

The X4 phenotype of HIV type 1 evolves from R5 in two children of mothers, carrying X4, and is not linked to transmission.

Previously, we found that emergence of the X4 viral phenotype in HIV-1-infected children was related to the presence of X4 in their mothers (C.H. Casper et al., J Infect Dis 2002; 186:914-921). Here, we investigated the origin of the X4 phenotype in the child, analyzing two mother-child pairs (Ma-Ca, Mb-Cb) where the mothers carried X4 and their children developed X4 after an initial presence of R5. We used nested polymerase chain reaction of the env V3 region to generate 203 HIV-1 clones for sequencing (Ma, n = 44; Ca, n = 73; Mb, n = 61; Cb, n = 25) from DNA of peripheral blood mononuclear cell (PBMC) lysates, altogether 167 clones, or from cDNA of plasma RNA, 36 clones. PBMC and plasma isolate sequences from each time point enabled us to assign the probable phenotype to clone sequences in a phylogenetic tree. The transmission and evolution were reconstructed using the maximum likelihood method. In mother-child pair Ma-Ca, one maternal R5 isolate clustered with the child's R5 sequences, at the earliest time when R5 was isolated in the child, confirming this as a likely source of the transmitted R5 phenotype. At age 3, an X4 population was present in the child that had evolved from the child's own R5-associated population, clearly distinct from the maternal X4 sequences. The second mother-child pair (Mb-Cb) displayed a similar pattern. Amino acid substitution patterns corroborated the conclusions from the phylogenetic tree. Thus, in both children, the X4 virus developed from their own R5 population, and was not caused by transmission of X4.

Amino Acid Sequence↗
PubMed1994

Reconstructing trees when sequence sites evolve at variable rates.

For a sequence of colors independently evolving on a tree under a simple Markov model, we consider conditions under which the tree can be uniquely recovered from the "sequence spectrum"-the expected frequencies of the various leaf colorations. This is relevant for phylogenetic analysis (where colors represent nucleotides or amino acids; leaves represent extant taxa) as the sequence spectrum is estimated directly from a collection of aligned sequences. Allowing the rate of the evolutionary process to vary across sites is an important extension over most previous studies-we show that, given suitable restrictions on the rate distribution, the true tree (up to the placement of its root) is uniquely identified by its sequence spectrum. However, if the rate distribution is unknown and arbitrary, then, for simple models, it is possible for every tree to produce the same sequence spectrum. Hence there is a logical barrier to accurate, consistent phylogenetic inference for these models when assumptions about the rate distribution are not made. This result exploits a novel theorem on the action of polynomials with non-negative coefficients on sequences.

Markov Chains↗
PubMed2002

The three mouse actin-depolymerizing factor/cofilins evolved to fulfill cell-type-specific requirements for actin dynamics.

Actin-depolymerizing factor (ADF)/cofilins are essential regulators of actin filament turnover. Several ADF/cofilin isoforms are found in multicellular organisms, but their biological differences have remained unclear. Herein, we show that three ADF/cofilins exist in mouse and most likely in all other mammalian species. Northern blot and in situ hybridization analyses demonstrate that cofilin-1 is expressed in most cell types of embryos and adult mice. Cofilin-2 is expressed in muscle cells and ADF is restricted to epithelia and endothelia. Although the three mouse ADF/cofilins do not show actin isoform specificity, they all depolymerize platelet actin filaments more efficiently than muscle actin. Furthermore, these ADF/cofilins are biochemically different. The epithelial-specific ADF is the most efficient in turning over actin filaments and promotes a stronger pH-dependent actin filament disassembly than the two other isoforms. The muscle-specific cofilin-2 has a weaker actin filament depolymerization activity and displays a 5-10-fold higher affinity for ATP-actin monomers than cofilin-1 and ADF. In steady-state assays, cofilin-2 also promotes filament assembly rather than disassembly. Taken together, these data suggest that the three biochemically distinct mammalian ADF/cofilin isoforms evolved to fulfill specific requirements for actin filament dynamics in different cell types.

Actin Depolymerizing Factors↗
PubMed2003

Direct evidence for a critical role of myosin II in budding yeast cytokinesis and the evolvability of new cytokinetic mechanisms in the absence of myosin II.

In the budding yeast Saccharomyces cerevisiae, an actomyosin-based contractile ring is present during cytokinesis, as occurs in animal cells. However, the precise requirement for this structure during budding yeast cytokinesis has been controversial. Here we show that deletion of MYO1, the single myosin II gene, is lethal in a commonly used strain background. The terminal phenotype of myo1Delta is interconnected chains of cells, suggestive of a cytokinesis defect. To further investigate the role of Myo1p in cytokinesis, we conditionally disrupted Myo1 function by using either a dominant negative Myo1p construct or a strain where expression of Myo1p can be shut-off. Both ways of disruption of Myo1 function result in a failure in cytokinesis. Additionally, we show that a myo1Delta strain previously reported to grow nearly as well as the wild type contains a single genetic suppressor that alleviates the severe cytokinesis defects of myo1Delta. Using fluorescence time-lapse imaging and electron microscopy techniques, we show that cytokinesis in this strain is achieved through formation of multiple aberrant septa. Taken together, these results strongly suggest that the actomyosin ring is crucial for successful cytokinesis in budding yeast, but new cytokinetic mechanisms can evolve through genetic changes when myosin II function is impaired.

Actomyosin↗
PubMed1991

Sequential echocardiographic-Doppler assessment of left ventricular remodelling and mitral regurgitation during evolving experimental heart failure.

STUDY OBJECTIVE: The aim was to study the nature, magnitude, and time course of left ventricular structural adaptations to evolving heart failure. DESIGN: 17 male mongrel dogs, weight 24.9(SD 3.7) kg, underwent rapid ventricular pacing (250 beats.min-1) until severe heart failure developed. Two dimensional echocardiographic and Doppler studies were performed at control, then weekly to severe heart failure. Haemodynamic measurements were made at control and severe heart failure. All studies were performed with the animals conscious during temporary sinus rhythm. MEASUREMENTS AND MAIN RESULTS: Left ventricular diastolic volume gradually increased and the left ventricle assumed a more globular shape associated with significant wall thinning. Both the change in diastolic volume after one week of pacing and at the time of severe heart failure correlated with the time to peak heart failure. Mitral regurgitation was mild after one week of pacing, became moderate in most animals at severe heart failure, and lagged temporarily behind the increase in cardiac dimensions. The percentage increase in mitral annular size was significantly less than the increase in left ventricular cross sectional area. CONCLUSIONS: In pacing induced heart failure (1) marked left ventricular remodelling occurs, (2) the extent of left ventricular dilatation, both early and late, correlates directly with the time required for the development of severe heart failure, (3) mitral regurgitation is an epiphenomenon and is most likely to be caused by the increase in left ventricular cross sectional area.

Animals↗
PubMed1996

Nucleotide sequence of the psbP gene encoding precursor of 23-kDa polypeptide of oxygen-evolving complex in Arabidopsis thaliana and its expression in the wild-type and a constitutively photomorphogenic mutant.

The psbP gene encoding the precursor of 23-kDa polypeptide of the oxygen-evolving complex of photosystem II has been isolated from Arabidopsis thaliana genomic library and sequenced. The gene harbors three introns and encodes a mature polypeptide of 186 amino acid residues and a transit peptide of 77 amino acid residues. The deduced molecular mass of the mature polypeptide is 23.5-kDa and it contains 22.6% charged amino acid residues which may contribute to the hydrophilic nature of the protein. The transcript encoded by psbP gene of Arabidopsis is approximately 1.3-kb long. In wild-type Arabidopsis seedlings, its expression is organ-specific and is regulated by endogenous developmental cues, light and sucrose. In a constitutively photomorphogenic mutant of Arabidopsis, designated as pho1, the psbP gene is partly derepressed in young, dark-grown seedlings, resulting in a slightly higher level of the transcript. Additionally, the pho1 mutant shows slow accumulation of psbP transcript upon illumination of young, dark-grown seedlings. However, the derepression is not markedly displayed on dark-adaptation of pho1 plants grown in continuous light. These studies, therefore, define the activity of at least one cellular effector involved in regulation of psbP expression.

Amino Acid Sequence↗
PubMed1998

The psbO gene for 33-kDa precursor polypeptide of the oxygen-evolving complex in Arabidopsis thaliana--nucleotide sequence and control of its expression.

The 33-kDa polypeptide of the oxygen-evolving complex of photosystem II is nuclear-encoded. The single psbO gene of Arabidopsis thaliana, as suggested by Southern hybridization, has been isolated from the genomic library and sequenced. The sequence analysis has revealed that the psbO gene harbors two introns and encodes a precursor polypeptide of 332 amino acid residues; the first 85 amino acid residues represent the transit peptide and the following 247 amino acids constitute the mature polypeptide. The hydrophilic nature of the 33-kDa protein is confirmed by the presence of 27% charged residues. Northern analysis of the total RNA from Arabidopsis indicates that a 1.2-kb transcript represents the psbO gene. It is expressed in a tissue-specific manner -- the steady-state transcript levels being highest in the leaves and virtually undetectable in the roots. Also, expression of the psbO gene is development-dependent and regulated by light in young Arabidopsis seedlings. In a constitutively photomorphogenic mutant of Arabidopsis, pho2 (plumular hook open 2), the psbO gene is de-repressed in young, dark-grown seedlings, resulting in increased transcript abundance compared to the wild-type. These studies, thus, define the influence of at least one regulatory component for psbO expression.

Amino Acid Sequence↗
PubMed1999

Nucleotide sequence of psbQ gene for 16-kDa protein of oxygen-evolving complex from Arabidopsis thaliana and regulation of its expression.

The psbQ gene encoding a 16-kDa polypeptide of the oxygen-evolving complex of photosystem II has been isolated from Arabidopsis thaliana and characterized. The gene consists of a 28 nucleotide long leader sequence, two introns and three exons encoding a 223-amino-acid precursor polypeptide. The first 75 amino acids act as a transit peptide for the translocation of the polypeptide into the thylakoid lumen. Expression studies show that the gene is light-inducible and expresses only in green tissues with high steady-state mRNA levels in leaves. Using this gene as a probe, restriction fragment length polymorphism between two ecotypes, Columbia and Estland, has also been detected.

Amino Acid Sequence↗