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At least 505 records · Page 28Linked to original sources
PubMed2001

Acute myelogenous leukemia with PIG-A gene mutation evolved from aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome.

We report a patient with aplastic anemia (AA)-paroxysmal nocturnal hemoglobinuria (PNH) syndrome who developed acute myelogenous leukemia (AML). Flow cytometric analysis showed that the leukemic cells in the bone marrow lacked CD59 antigen on their surface and were positive for P-glycoprotein. Heteroduplex and single-strand conformation polymorphism analysis followed by sequencing of the leukemic cells in the bone marrow disclosed 1 frameshift-type mutation in exon 2 of the phosphatidylinositol glycan-class A (PIG-A) gene, which deductively produces truncated PIG-A protein. These findings provide direct evidence that the leukemic cells evolved from the affected PNH clone. Cytogenetic analysis in the bone marrow in each stage of AA-PNH, AML, and at relapse of AML showed normal, -7, and -7 plus -20, respectively, showing evidence of a clonal evolution. Because complete remission of AML was not achieved by intensive chemotherapies, allogeneic peripheral blood stem cell transplantation (PBSCT) from the patient's HLA-matched sister was performed successfully with recovery of CD59 antigen on bone marrow hematopoietic cells; however, leukemia relapsed 4 months after PBSCT. Leukemia derived from PNH may be resistant to intensive chemotherapy, and a highly myeloablative regimen may be required for stem cell transplantation to eradicate the PNH-derived leukemia clone.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Two cases of acute myeloblastic leukemia evolving from aplastic anemia.

Two cases of acute myeloblastic leukemia (AML) evolving from aplastic anemia are presented. The first case was diagnosed 18 years ago, and treatment with bolus methylprednisolone, prednisolone, and androgens resulted in partial hematological response. Severe pancytopenia recurred, and AML M0 by French-American-British classification developed. The second case was diagnosed 7 years ago. The patient had HLA DRB1*1501, and treatment with granulocyte colony-stimulating factor (G-CSF), cyclosporine, and methenolone resulted in complete hematological response. Thrombocytopenia recurred and did not respond to cyclosporine and methenolone or to later treatment with antithymocyte globulin, and AML M1 developed. Cytogenetic studies demonstrated 7q- in the first patient and +8 in the second patient. No mutations of N-ras or p53 were observed in either patient. These patients were treated with cytosine arabinoside, aclacinomycin, and G-CSF (CAG) chemotherapy, and the number of leukemic cells decreased substantially. However, pancytopenia after CAG chemotherapy persisted, and the first patient died of pneumonia and the second patient of cerebral hemorrhage.

Anemia, Aplastic↗
PubMed1997

Normal thyroxine and elevated thyrotropin concentrations: evolving hypothyroidism or persistent euthyroidism with reset thyrostat.

BACKGROUND: The natural course in subjects manifesting normal serum thyroxine (T4), and triiodothyronine (T3), with an elevated thyrotropin (TSH) level demonstrated two distinct outcomes, one progressing to well defined hypothyroidism as expressed by onset of subnormal T4, T3 and a further rise in TSH and the other remaining in the same state. However, thyroid hormone concentrations at the time of diagnosis fail to distinguish between the two groups. Therefore, we examined the influence of alteration in circulating TSH levels on thyroid gland function at the time of diagnosis in subjects with this syndrome to assess the role of pituitary thyroid axis in these different outcomes. METHODS: 24 hour 131I thyroidal uptake was determined in 14 men and 3 women manifesting normal T4, T3 and elevated TSH prior to and again after 1) subcutaneous administration of bovine TSH, 10 units daily for 3 days and 2) daily oral administration of L-triiodothyronine 75 micrograms for 7 days in a randomized sequence at interval of 4 weeks. Subjects were then followed for up to 16 years to assess the natural course. RESULTS: Basal 24 hour 131I uptake values were within the normal range (10-35%) in all subjects and increased on TSH administration and declined following LT3 administration. However, in eight subjects, these responses were markedly lower (< 20%) when compared with the minimum change (50%) noted in normal volunteers. These subjects progressed to manifest hypothyroidism requiring LT4 therapy within two years as reflected by a progressive decrease to subnormal T4 levels with a further rise in serum TSH. The remaining nine subjects, demonstrated normal responses (> 50%) and only one of these became hypothyroid during the follow-up period of 16 years. CONCLUSION: All subjects with normal T4 and T3 with elevated TSH do not manifest "subclinical or evolving hypothyroidism". Two distinct populations seem to exist, one with inhibited pituitary thyroid axis progressing to hypothyroidism or true "subclinical hypothyroidism" at the time of diagnosis and the other with normal pituitary thyroid axis, a state of euthyroidism with "reset thyrostat" at a higher TSH concentration, a state probably persisting for their remaining life span.

Adult↗
PubMed1997

Nonplastid eukaryotic response regulators have a monophyletic origin and evolved from their bacterial precursors in parallel with their cognate sensor kinases.

We have analyzed all currently sequenced eukaryotic proteins containing either a kinase module or a receiver module, corresponding to those found in bacterial sensor kinases or response regulators, respectively, of the so-called two-component regulatory systems. We demonstrate that the eukaryotic receiver modules belong to a single subfamily of the bacterial receiver modules. Moreover, the cognate eukaryotic kinase modules exhibit a similar clustering pattern on the sensor kinase phylogenetic tree, suggesting that they evolved in parallel with the receiver modules from a common ancestral source that bore both modules. Multiple alignments of the sequences corresponding to these modules are presented and discussed, and eukaryotic-specific signature sequences are derived.

Amino Acid Sequence↗
PubMed2000

Interaction of nitric oxide with the oxygen evolving complex of photosystem II and manganese catalase: a comparative study.

We compare the interaction of nitric oxide with the S states of the oxygen evolving complex (OEC) of photosystem II and the dinuclear Mn cluster of Thermus thermophilus catalase. Flash fluorescence studies indicate that the S3 state of the OEC in the presence of ca. 0.6 mM NO is reduced to the S1 with an apparent halftime of ca. 0.4 s at about 18 degrees C, compared with a biphasic decay, with approximate halftimes of 28 s for S3 to S2 and 140 s for S2 to S1 in the absence of NO. Under similar conditions the S2 state is reduced by NO to the S1 state with an approximate halftime of 2 s. These results extend a recent study indicating a slow reduction of the S1 state at -30 degrees C, via the S0 and S(-1) states, to a Mn(II)-Mn(III) state resembling the corresponding state in catalase. The reductive mode of action of NO is repeated with the di-Mn cluster of catalase: the Mn(III)-Mn(III) redox state is reduced to the Mn(II)-Mn(II) state via the intermediate Mn(II)-Mn(III) state. The kinetics of this reduction suggest a decreasing reduction potential with decreasing oxidation state, similar to what is observed with the active states of the OEC. What is unique about the OEC is the rapid interaction of NO with the S3 state of the OEC, which is compatible with a metalloradical character of this state.

Catalase↗
PubMed2003

Lectin-related resistance factors against bruchids evolved through a number of duplication events.

Abundant lectin-related proteins found in common beans ( Phaseolus vulgaris L.) have been shown to confer resistance against the larvae of a number of bruchid species. Genes encoding for these proteins are members of the lectin multigene family, the most representative components being arcelins, phytohemagglutinins and alpha-amylase inhibitors. Arcelins have been described in seven variants, some of which are resistance factors against the Mexican bean weevil ( Zabrotes subfasciatus), a major bean predator. In this study the isolation and sequencing of arcelin genes from wild P. vulgaris genotypes, containing Arc3 and Arc7 variants, is reported, and similarities and evolutionary relationships among the seven known arcelins are described. The evolutionary analysis shows that arcelins 3 and 4 cluster together and are the most-ancient variants. A duplication event gave rise to two additional clusters, one comprising arcelins 1, 2 and 6 and separated from the cluster of arcelins 5 and 7. A multiple number of arcelin genes were found in arcelin 3 and 4 genotypes indicating that more than one type of arcelin gene may be present in the same locus. Some of these sequences are reminiscent of ancient duplication events in arcelin evolution demonstrating that arcelins have evolved through multiple duplications. A further aim of this paper was to better understand and describe the evolution of the entire lectin multigene family. Beside arcelins, a number of other types of sequences, such as putative lectins and sequences not easily classifiable, were found in genotypes containing Arc3 and Arc4. These results, together with the evolutionary analysis, indicate that lectin loci are quite complex and confirm their origin by multiple duplication events.

Amino Acid Sequence↗
PubMed2003

Tightly linked di- and tri-nucleotide microsatellites do not evolve in complete independence: evidence from linked (TA)n and (TAA)n microsatellites of chickpea (Cicer arietinum L.).

In order to understand the dynamics of microsatellite evolution, we have studied allelic variation at a closely linked (TA)(n) and (TAA)(n) microsatellite loci in 114 land races of chickpea ( Cicer arietinum L.), sampled worldwide. These two loci are separated by 27 bp. The two loci showed a very high degree of polymorphism and hence the combined length with the genetic diversity of 0.93, 0.90 and 0.98 for (TAA)(n), (TA)(n) and the combined length, respectively. Using the variation data at the linked loci, a standardized index of linkage disequilibrium was also computed ( I(S)(A)=0.092), which tests the null hypothesis of no linkage and was significant, indicating the presence of linkage disequilibrium. Furthermore, the dynamics of allelic variation showed that there is a threshold combined length, below which both (TAA)(n) and (TA)(n) loci evolve independently, and above which, if one locus increase in size, the other closely linked locus has a tendency to decrease its size and vice versa, without change in the overall ratio of (TAA)(n) and (TA)(n) allele sizes at the region. This result indicates that there are processes in the cell, which 'read' the combined size of the two loci both for proportion and length and determine the direction of tightly linked di- and tri-nucleotide repeat evolution.

Alleles↗
PubMed2005

Mitochondrial genetic codes evolve to match amino acid requirements of proteins.

Mitochondria often use genetic codes different from the standard genetic code. Now that many mitochondrial genomes have been sequenced, these variant codes provide the first opportunity to examine empirically the processes that produce new genetic codes. The key question is: Are codon reassignments the sole result of mutation and genetic drift? Or are they the result of natural selection? Here we present an analysis of 24 phylogenetically independent codon reassignments in mitochondria. Although the mutation-drift hypothesis can explain reassignments from stop to an amino acid, we found that it cannot explain reassignments from one amino acid to another. In particular--and contrary to the predictions of the mutation-drift hypothesis--the codon involved in such a reassignment was not rare in the ancestral genome. Instead, such reassignments appear to take place while the codon is in use at an appreciable frequency. Moreover, the comparison of inferred amino acid usage in the ancestral genome with the neutral expectation shows that the amino acid gaining the codon was selectively favored over the amino acid losing the codon. These results are consistent with a simple model of weak selection on the amino acid composition of proteins in which codon reassignments are selected because they compensate for multiple slightly deleterious mutations throughout the mitochondrial genome. We propose that the selection pressure is for reduced protein synthesis cost: most reassignments give amino acids that are less expensive to synthesize. Taken together, our results strongly suggest that mitochondrial genetic codes evolve to match the amino acid requirements of proteins.

Amino Acids↗
PubMed2004

Phylogenetic analysis of the complete genome sequence of Encephalitozoon cuniculi supports the fungal origin of microsporidia and reveals a high frequency of fast-evolving genes.

Microsporidia are unicellular eukaryotes living as obligate intracellular parasites. Lacking mitochondria, they were initially considered as having diverged before the endosymbiosis at the origin of mitochondria. That microsporidia were primitively amitochondriate was first questioned by the discovery of microsporidial sequences homologous to genes encoding mitochondrial proteins and then refuted by the identification of remnants of mitochondria in their cytoplasm. Various molecular phylogenies also cast doubt on the early divergence of microsporidia, these organisms forming a monophyletic group with or within the fungi. The 2001 proteins putatively encoded by the complete genome of Encephalitozoon cuniculi provided powerful data to test this hypothesis. Phylogenetic analysis of 99 proteins selected as adequate phylogenetic markers indicated that the E. cuniculi sequences having the lowest evolutionary rates preferentially clustered with fungal sequences or, more rarely, with both animal and fungal sequences. Because sequences with low evolutionary rates are less sensitive to the long-branch attraction artifact, we concluded that microsporidia are evolutionarily related to fungi. This analysis also allowed comparing the accuracy of several phylogenetic algorithms for a fast-evolving lineage with real rather than simulated sequences.

Animals↗
PubMed2006

Tandem repetitive D domains of the sperm ligand zonadhesin evolve faster in the paralogue than in the orthologue comparison.

Gene duplication is regarded as an important evolutionary mechanism creating genetic and phenotypic novelty. At the same time, the evolutionary mechanisms following gene duplication have been a subject of much debate. Here we analyze the sequence evolution of zonadhesin, a mammalian sperm ligand that binds to the oocyte zona pellucida in a species-specific manner. In pig, rabbit, and primates, precursor zonadhesin comprises, among others, one partial and four complete tandem repetitive D domains. The mouse precursor is distinguished by 20 additional partial D3 domains consisting of 120 amino acids each. This gene structure allows sequence comparison in both paralogues and orthologues. Detailed sequence analysis reveals that D domains evolve faster across paralogues than orthologues. Moreover, at the codon level, partial D3 paralogues of mouse show evidence of positive selection, whereas the corresponding orthologues do not. Individual posttranslational motif patterns and positive selection point to neofunctionalization of partial D3 paralogues of mouse, rather than subfunctionalization. However, as we found additional evidence for homogenization by partial gene conversion, sequence evolution of partial D3 paralogues of mouse might be better described as a combination of divergent and convergent evolution. So far, the divergence at the codon level has outbalanced the convergence at the level of smaller fragments. The probable driving force behind the evolutionary patterns observed is sexual selection. We finally discuss whether the functional determination influences the evolutionary regime acting on sperm ligands and egg receptors, respectively.

Amino Acid Motifs↗
PubMed2000

Phylogeny of ultra-rapidly evolving dinoflagellate chloroplast genes: a possible common origin for sporozoan and dinoflagellate plastids.

Complete chloroplast 23S rRNA and psbA genes from five peridinin-containing dinoflagellates (Heterocapsa pygmaea, Heterocapsa niei, Heterocapsa rotun-data, Amphidinium carterae, and Protoceratium reticulatum) were amplified by PCR and sequenced; partial sequences were obtained from Thoracosphaera heimii and Scrippsiella trochoidea. Comparison with chloroplast 23S rRNA and psbA genes of other organisms shows that dinoflagellate chloroplast genes are the most divergent and rapidly evolving of all. Quartet puzzling, maximum likelihood, maximum parsimony, neighbor joining, and LogDet trees were constructed. Intersite rate variation and invariant sites were allowed for with quartet puzzling and neighbor joining. All psbA and 23S rRNA trees showed peridinin-containing dinoflagellate chloroplasts as monophyletic. In psbA trees they are related to those of chromists and red algae. In 23S rRNA trees, dinoflagellates are always the sisters of Sporozoa (apicomplexans); maximum likelihood analysis of Heterocapsa triquetra 16S rRNA also groups the dinoflagellate and sporozoan sequences, but the other methods were inconsistent. Thus, dinoflagellate chloroplasts may actually be related to sporozoan plastids, but the possibility of reproducible long-branch artifacts cannot be strongly ruled out. The results for all three genes fit the idea that dinoflagellate chloroplasts originated from red algae by a secondary endosymbiosis, possibly the same one as for chromists and Sporozoa. The marked disagreement between 16S rRNA trees using different phylogenetic algorithms indicates that this is a rather poor molecule for elucidating overall chloroplast phylogeny. We discuss possible reasons why both plastid and mitochondrial genomes of alveolates (Dinozoa, Sporozoa and Ciliophora) have ultra-rapid substitution rates and a proneness to unique genomic rearrangements.

Animals↗
PubMed1996

Chronic recurrent multifocal osteomyelitis: an evolving clinical and radiological spectrum.

OBJECTIVE: To describe unusual clinical and radiological features in patients with chronic recurrent multifocal osteomyelitis (CRMO). DESIGN AND SUBJECTS: Based on radiographic and microscopic findings, three patients were prospectively diagnosed as having chronic recurrent multifocal osteomyelitis (CRMO). They form the basis of this report because of either the unusualness of the clinical presentation, hitherto undescribed associated diseases or the unusual age of presentation and sites of lesions. RESULTS: One patient developed pyoderma gangrenosum at the site of one of the skeletal lesions and then went on to develop ulcerative proctitis. A second patient presented with a soft tissue mass, which on MRI mimicked a sarcoma. The final patient presented with lesions in the wrist and phalanges of the toes at the unusual age of 38. None of the patients was treated with steroids or antibiotics for the skeletal lesions. Steroids were administered to one patient for treatment of pyoderma gangrenosum. CONCLUSIONS: The pattern and distribution of skeletal lesions in CRMO are well recognized in the pediatric age group. The unusual clinical and/or radiological features discussed herein suggests that this is a disease that continues to evolve with a broader spectrum of features than recognized.

Adult↗
PubMed2005

The dynamical way to mutation-selection balance of an infinite population evolving on a truncated fitness landscape.

This paper presents the exact analytical solution, valid for all generations and initial conditions, for the frequency distribution of haploids with infinite-sites genome carrying a given number of mutations in a population evolving deterministically on a truncated fitness landscape. This landscape is a generalization of the single sharp peak one, widely used in quasispecies theory, although here there are no reverse mutations.

Animals↗
PubMed2002

C4 deficiency state in antiphospholipid antibody-related recurrent preeclampsia evolving into systemic lupus erythematosus.

The case of an apparent healthy woman who developed recurrent preeclampsia with antiphospholipid antibodies and evolved towards systemic lupus erythematosus during her last pregnancy is presented. The diagnostic dilemma between lupus renal flare and toxemia is discussed. The potential role of immunological alterations, such as complement genetic deficiencies, in women with primary antiphospholipid syndrome who develop systemic lupus erythematosus is also discussed.

Adult↗
PubMed1997

Morphological characterization of the evolving rat spinal cord injury after photochemically induced ischemia.

We have characterized the evolving morphological changes in the adult rat spinal cord following photochemically induced spinal cord ischemia. In cresyl violet-stained sections, disintegration of the tissue at the epicenter was evident at 6 h. This was preceded at 1 h post ischemia by an albumin immunoreactivity. The albumin immunoreactivity was increased at 6 and even more so at 24 h post ischemia. At 72 h post ischemia the albumin immunoreactivity was decreased. The size of the lesion was established by 3 days after the onset of ischemia. During the 1st week post ischemia, neurofilament (NF) immunohistochemistry showed swollen axons adjacent to the injured tissue. From 2 weeks post ischemia an increasing number of regrowing NF-immunoreactive axons could be seen in the center of the necrotic cavity. At 3 weeks after ischemia, a developing gliosis was observed around and rostral to the lesion cavity, as evidenced by increased glial fibrillary acidic protein (GFAP) immunoreactivity. The gliosis became more pronounced until 6 weeks post ischemia, at which time enlarged GFAP-immunoreactive cells could be seen in the remaining viable tissue bordering the necrotic areas. In this study we show that several traits in the development of a spinal cord lesion after photochemically induced ischemia are similar to those described previously after traumatic spinal cord lesions.

Animals↗
PubMed2000

Report of a patient with aortic dissection evolving into binocular ischemic retinopathy.

BACKGROUND: Carotid artery disease is known to cause a variety of ischemic ocular syndromes. We report a patient with an aortic dissection that evolved into binocular ischemic retinopathy. METHODS: Case report. RESULTS: A 49-year-old male patient presented with stomach pains and with no ophthalmologic symptoms. After extensive examination, a diagnosis of aortic dissection was made to account for the acute abdominal pain. Sixteen days later, he noted binocular photopsia and ophthalmoscopy revealed ischemic retinopathy. Arterial stent implantation and right coronary reconstitution surgery were performed. Subsequently, the ischemic lesions in the retina disappeared and no abnormality was observed by retinal angiography 1 year later. CONCLUSION: Binocular ischemic retinopathy can be a sign of aortic or carotid dissection, and these observations suggest that aortic dissection should be included in the differential diagnosis whenever ischemic changes are detected in the retina.

Aortic Dissection↗
PubMed2006

Glyphosate, paraquat and ACCase multiple herbicide resistance evolved in a Lolium rigidum biotype.

Glyphosate is the world's most widely used herbicide. A potential substitute for glyphosate in some use patterns is the herbicide paraquat. Following many years of successful use, neither glyphosate nor paraquat could control a biotype of the widespread annual ryegrass (Lolium rigidum), and here the world's first case of multiple resistance to glyphosate and paraquat is confirmed. Dose-response experiments established that the glyphosate rate causing 50% mortality (LD(50)) for the resistant (R) biotype is 14 times greater than for the susceptible (S) biotype. Similarly, the paraquat LD(50 )for the R biotype is 32 times greater than for the S biotype. Thus, based on the LD(50 )R/S ratio, this R biotype of L. rigidum is 14-fold resistant to glyphosate and 32-fold resistant to paraquat. This R biotype also has evolved resistance to the acetyl-coenzyme A carboxylase (ACCase) inhibiting herbicides. The mechanism of paraquat resistance in this biotype was determined as restricted paraquat translocation. Resistance to ACCase-inhibiting herbicides was determined as due to an insensitive ACCase. Two mechanisms endowing glyphosate resistance were established: firstly, a point mutation in the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene, resulting in an amino acid substitution of proline to alanine at position 106; secondly, reduced glyphosate translocation was found in this R biotype, indicating a co-occurrence of two distinct glyphosate resistance mechanisms within the R population. In total, this R biotype displays at least four co-existing resistance mechanisms, endowing multiple resistance to glyphosate, paraquat and ACCase herbicides. This alarming case in the history of herbicide resistance evolution represents a serious challenge for the sustainable use of the precious agrochemical resources such as glyphosate and paraquat.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗
PubMed2002

Laparoscopic radiofrequency ablation and hepatic artery infusion pump placement in the evolving treatment of colorectal hepatic metastases.

BACKGROUND: Laparoscopic radiofrequency ablation (LRFA) and laparoscopic hepatic artery infusion pump (LHAIP) placement are new treatment options for patients with colorectal liver metastases. This study investigates the selection criteria, safety, efficacy, and preliminary outcomes of patients treated with LRFA and LHAIP placement. METHODS: Fourty five patients with colorectal metastases confined to the liver, 37 of whom had failed systemic chemotherapy, were treated with LRFA and/or LHAIP between September 1996 and December 2001. Treatment selection was individualized, based on each patient's general health, liver function, and tumor size, number, location, and distribution. RESULTS: Twenty patients (44%) had LRFA alone, 10 (22%) had LHAIP placement alone, and 15 (33%) patients had combined LRFA and LHAIP therapy. The LRFA group had a significantly shorter mean operative time and blood loss (p <0.05), but hospital stays were similar when compared to patients receiving LRFA + LHAIP or LHAIP alone. Tumor characteristics were worse in both LHAIP groups, with a higher incidence of tumors >or=4 cm, major vascular involvement, diffuse tumor pattern, bilobar distribution, and involvement of more than three segments. During a mean follow-up period of 11.5 +/- 7.8 months (range, 1-38), the actuarial survival was 70%, 67%, and 50% for LRFA, LRFA + LHAIP, and LHAIP, respectively. LHAIP only patients had the shortest estimated mean survival time of the three groups by Kaplan-Meier survival curves (p = 0.001). CONCLUSION: LRFA and/or LHAIP placement are safe and feasible treatment options for the treatment of colorectal hepatic metastases. The choice of treatment for patients should be based primarily on tumor characteristics. Long-term studies, which will elucidate the role of these evolving treatments, are now under way.

Adult↗