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PubMedDate not supplied

Molecular characterization of G6PD deficiency in Cyprus.

In the present study, we determined the frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Cyprus using two different procedures in two separate adult population groups: a semiquantitative fluorescence test on blood spotted on filter paper and a quantitative spectrophotometric test on liquid blood. The frequency of G6PD deficiency among healthy adult males was found to be 5.1% using the semiquantitative procedure and 6.4% using the quantitative procedure. Neither method was able to detect all the expected female heterozygotes (5.3% and 47.1% of the expected number, respectively). A total of 21 male hemizygotes, 1 female homozygote and 9 female heterozygotes that tested positive for G6PD deficiency were studied at the molecular level. All 32 chromosomes were genotyped and five different mutations were identified. The Mediterranean mutation in exon 6 (563C-->T) (Ser188Phe) was found to be the most common variant in the Cypriot population, accounting for 52.6% of the deficient alleles. In the remaining chromosomes, four different mutations were identified: three known mutations, Kaiping 1388G-->A (Arg463His), Chatham 1003G-->A (Ala335Thr) and Acrokorinthos 463C-->G (His155Asp), and one previously undescribed mutation in exon 3, 148C-->T (Pro50Ser), which we called G6PD Kambos. We conclude that the frequency of G6PD deficiency in Cypriot males is 6.4%, and that this deficiency is the result of several different mutations. Although all the individuals carrying the Mediterranean variant can be detected using a semiquantitative screening method, a quantitative enzyme measurement is required to detect the G6PD variants with less severe enzyme deficiencies, while the most appropriate method for heterozygote detection is DNA analysis.

Clinical Laboratory Techniques↗
PubMed1992

The desmo- and osteoplastic ameloblastoma. Histologic variant or clinicopathologic entity? Case reports.

Two cases of desmoplastic ameloblastoma (DA) are presented, bringing the total number of reported cases to 29. One case of the so-called "hybrid lesion" is added to the presentation. Immunohistochemical studies indicate that the desmoplasia is caused by active de novo synthesis of extracellular matrix proteins. Moreover, the DA may also show osteoplasia, and this probably explains the characteristic radiographic appearance of many DAs, i.e. the occurrence of both radiolucent and radiopaque changes, suggestive of a fibro-osseous lesion. Many more cases of DA are needed to clarify the true nature of this most interesting tumor.

Adult↗
PubMed1991

Hypothesis testing as an approach to the analysis of complex tachycardias--an illustrative case of a preexcitation variant.

The correct elucidation of the electrophysiological substrate and mechanism(s) responsible for a complex arrhythmia requires a systematic approach to the analysis of the electrophysiological data. One approach calls for the formulation of a set of hypotheses that could explain the data obtained during the study. The hypotheses are then tested for compatibility with phenomena observed and the one that agrees with the majority of the findings would represent the most tenable explanation. We present the case of a young girl with a wide QRS complex tachycardia and a history of ventricular preexcitation that illustrates this approach. The complexities were resolved only after intraoperative analysis and surgical ablation of a right-sided accessory pathway with decremental properties, and provides further insight into our understanding of the nodoventricular Mahaim fiber.

Anti-Arrhythmia Agents↗
PubMed2006

Hearing improvement in a patient with variant Muckle-Wells syndrome in response to interleukin 1 receptor antagonism.

BACKGROUND: Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome, and neonatal onset multisystem inflammatory disease, also called chronic, infantile, neurological, cutaneous, and articular syndrome, are three hereditary autoinflammatory syndromes caused by mutations affecting the CIAS1/NALP3 gene on chromosome 1q44. The proinflammatory cytokine, interleukin 1beta, is believed to have a fundamental role in their pathogenesis. CASE REPORT: The case is described of a 59 year old white woman who presented with increasingly severe MWS-type features over a 15 year period. The response to interleukin 1beta inhibition with anakinra was dramatic, including a reduction in intracranial pressure with associated auditory improvement, as demonstrated by serial audiometry. CONCLUSIONS: The confirmed improvement in hearing after initiation of interleukin 1 receptor antagonism corroborates previous reports that specific blockade of this single cytokine reverses most of the symptoms of this group of CIAS1/NALP3 related autoinflammatory conditions, including the sensorineural deafness, which has not been previously reported.

Antirheumatic Agents↗
PubMed2005

Imidazolinone-tolerant crops: history, current status and future.

Imidazolinone herbicides, which include imazapyr, imazapic, imazethapyr, imazamox, imazamethabenz and imazaquin, control weeds by inhibiting the enzyme acetohydroxyacid synthase (AHAS), also called acetolactate synthase (ALS). AHAS is a critical enzyme for the biosynthesis of branched-chain amino acids in plants. Several variant AHAS genes conferring imidazolinone tolerance were discovered in plants through mutagenesis and selection, and were used to create imidazolinone-tolerant maize (Zea mays L), wheat (Triticum aestivum L), rice (Oryza sativa L), oilseed rape (Brassica napus L) and sunflower (Helianthus annuus L). These crops were developed using conventional breeding methods and commercialized as Clearfield* crops from 1992 to the present. Imidazolinone herbicides control a broad spectrum of grass and broadleaf weeds in imidazolinone-tolerant crops, including weeds that are closely related to the crop itself and some key parasitic weeds. Imidazolinone-tolerant crops may also prevent rotational crop injury and injury caused by interaction between AHAS-inhibiting herbicides and insecticides. A single target-site mutation in the AHAS gene may confer tolerance to AHAS-inhibiting herbicides, so that it is technically possible to develop the imidazolinone-tolerance trait in many crops. Activities are currently directed toward the continued improvement of imidazolinone tolerance and development of new Clearfield* crops. Management of herbicide-resistant weeds and gene flow from crops to weeds are issues that must be considered with the development of any herbicide-resistant crop. Thus extensive stewardship programs have been developed to address these issues for Clearfield* crops.

Acetolactate Synthase↗
PubMed2000

A novel type of receptor protein, based on the lipocalin scaffold, with specificity for digoxigenin.

We demonstrate that the bilin-binding protein, a member of the lipocalin family of proteins, can be structurally reshaped in order to specifically complex digoxigenin, a steroid ligand commonly used for the non-radioactive labelling of biomolecules. 16 amino acid residues, distributed across the four loops which form the binding site of the bilin-binding protein, were subjected to targeted random mutagenesis. From the resulting library the variant DigA16 was obtained by combined use of phage display and a filter-sandwich colony screening assay, followed by in vitro affinity maturation. DigA16 possesses strong binding activity and high specificity for the digoxigenin group, with a K(D) of 30.2(+/-3.6) nM. The derivative compound digitoxigenin is bound even more tightly, with a K(D) of 2.0(+/-0.52) nM, whereas the steroid glycoside ouabain is not recognized at all. Fusion proteins between DigA16 and alkaline phosphatase were constructed and shown to retain both the digoxigenin-binding function and enzymatic activity, irrespective of whether the enzyme was fused to the N or the C terminus of the bilin-binding protein variant. Our findings suggest that the lipocalin scaffold can be generally employed for the construction of specific receptor proteins, so-called "anticalins", which provide a promising alternative to recombinant antibody fragments.

Alkaline Phosphatase↗
PubMed1999

The neurofibromatoses. An overview.

The last two decades have seen clinical and molecular delineation of the different forms of neurofibromatosis. Differentiation of these forms is not just an academic exercise: their natural history, management and genetic counselling are quite different. Of the numerical classifications of neurofibromatosis proposed in the past, only neurofibromatosis type 1 (Nf1) and neurofibromatosis type 2 (Nf2) are now well delineated clinically and have been shown to be distinct at the molecular level. For both forms of neurofibromatosis, patients with clinical generalised disease have been demonstrated to be mosaic at the molecular level, and features of segmental or mosaic Nf1 and Nf2 have been delineated. Other reported forms of neurofibromatosis are rarer; they include Watson syndrome, hereditary spinal neurofibromatosis, familial intestinal neurofibromatosis, autosomal dominant café-au-lait spots alone, autosomal dominant neurofibromas alone, and schwannomatosis, the latter believed to be a variant of Nf2. Further delineation is needed for individuals having overlapping features of Noonan's syndrome and neurofibromatosis (the so-called Noonan/neurofibromatosis syndrome) and the syndrome of "multiple naevi, multiple schwannomas and multiple vaginal leiomyomas". In this article we review the forms of neurofibromatosis which we believe are true clinical entities. Particular attention is given to the neurological manifestations of neurofibromatosis.

Humans↗
PubMed1993

beta-D-glucosyl-hydroxymethyluracil: a novel modified base present in the DNA of the parasitic protozoan T. brucei.

We have previously shown that the DNA of the unicellular eukaryote T. brucei contains about 0.1% of a novel modified base, called J. The presence of J correlates with a DNA modification associated with the silencing of telomeric expression sites for the variant surface antigens of trypanosomes. Here we show that J is 5-((beta-D-glucopyranosyloxy)-methyl)-uracil (shortened to beta-D-glucosyl-hydroxymethyluracil), a base not previously found in DNA. We discuss putative pathways for the introduction of this base modification at specific positions in the DNA and the possible contribution of this modification to repression of surface antigen gene expression.

Animals↗
PubMed2004

Proteins with simplified hydrophobic cores compared to other packing mutants.

Efforts to design proteins with greatly reduced sequence diversity have often resulted in proteins with so-called molten globule properties. Substitutions were made at six neighboring sites in the major hydrophobic core of staphylococcal nuclease to create variants with all leucine, all isoleucine or all valine at these sites. The mutant proteins with simplified cores constructed here are quite unstable and have poorly packed cores, attested to by interaction energies. Eight related mutants with greater sequence diversity were also constructed. Comparison to these mutants and 159 other permutations of these 3 aliphatic side chains at these same 6 sites previously constructed shows that the simplified cores are not unusual in their stabilities or interaction energies. Further, crystal structures of the two mutants with the worst packing, as measured by interaction energies, showed no unusual disorder in the core. Therefore, reduction of sequence diversity is not necessarily incompatible with a single stable native structure. Other factors must also contribute to previous protein design failures.

Crystallization↗
PubMed1995

Development and heterogeneity of prolactin cells.

Prolactin (PRL) is synthesized in pituitary cells called mammotrophs (PRL cells). Ample evidence demonstrates that the PRL cell population consists of structurally and functionally heterogeneous PRL cells. Multiple variants of PRL molecules are found in various species. Prolactin cells may be divided into various subtypes in the rat and mouse. Secretory activities differ among the PRL cell population. These heterogeneities may reflect various phases of the maturation process of PRL cells, or the integrated outcome of various functional differences in PRL cells. To clarify the significance of heterogeneities among PRL cells, we present updated reports on the differentiation, proliferation, and development of PRL cells, and discuss factors responsible for the functional differences in PRL cell population. The age-related alteration in PRL secretion in the rat is summarized, because it is one of the most important aspects of the developmental changes in PRL cells. A mammosomatotroph, which secretes growth hormone and PRL, is found in various species. Prolactin cells and somatotrophs are derived from the same lineage. The possible relationship among PRL cells, somatotrophs, and mammosomatotrophs is discussed.

Aging↗
PubMed1983

Computerized axial tomography in clumsy children with developmental apraxia and agnosia.

Fifty-one children who were clumsy because of perceptual disabilities and/or defects of motor organization were surveyed with computerized axial tomographic (CT) head scanning and compared to 33 controls by using both linear measurements and visual appraisal of the scans. Thirty-nine percent of these so-called clumsy children described as having developmental apraxia and agnosia, compared to 9% of the controls, were either abnormal or normal variants. These presumed abnormalities included ventricular dilatation, peripheral atrophy and parenchymal lesions. The Evans Ratio and Intercaudate Distance in the clumsy children were not significantly different from the controls, but the Ventricular Area Index was found to be very significantly different in the two groups.

Agnosia↗
PubMed1989

Thermodynamic and enzymological characterization of the interaction between transcription termination factor rho and lambda cro mRNA.

Termination of transcription at tR1, the rho-dependent terminator between genes cro and cII of bacteriophage lambda, is mediated by interactions between rho protein and an RNA sequence element called rut. We show, using a filter retention assay technique, that rho protein binds with about 10-fold lower affinity to variants of cro RNA lacking both parts of rut or to normal cro RNA having one or the other part of rut bound to a complementary DNA oligonucleotide than it binds to unmodified cro RNA. These same variant and modified forms are nearly devoid of the strong rho ATPase cofactor activity of cro RNA. Estimates of binding energies of the rho-cro RNA interaction under different conditions reveal that termination function correlates with about 12.6 kcal of binding energy, of which two-thirds is due to nonelectrostatic interactions. The rut segment is shown to contribute about 1 kcal, nearly all to nonelectrostatic interactions. KCl is found to be more effective than potassium glutamate as a competitive counterion, and a decrease in 1.4 kcal of binding energy due to counterion competition correlates with a loss of termination and ATPase activities. In sum, the results indicate that the rut sequence contributes substantially to the overall binding affinity, that ionic interactions are also important, and that mere binding of rho to RNA is not sufficient for rho ATPase activation.

Adenosine Triphosphatases↗
PubMed2004

Prevention of domain swapping inhibits dimerization and amyloid fibril formation of cystatin C: use of engineered disulfide bridges, antibodies, and carboxymethylpapain to stabilize the monomeric form of cystatin C.

Amyloidogenic proteins like cystatin C and prion proteins have been shown to form dimers by exchange of subdomains of the monomeric proteins. This process, called "three-dimensional domain swapping," has also been suggested to play a part in the generation of amyloid fibrils. One variant of cystatin C, L68Q cystatin C, is highly amyloidogenic, and persons carrying the corresponding gene suffer from massive cerebral amyloidosis leading to brain hemorrhage and death in early adult life. The present work describes the production of two variants of wild type and L68Q cystatin C with disulfide bridges at positions selected to inhibit domain swapping without affecting the biological function of the four cystatin C variants as cysteine protease inhibitors. The capacity of the four variant proteins to form dimers was tested and compared with that of wild type and L68Q cystatin C. In contrast to the latter two proteins, all four protein variants stabilized by disulfide bridges were resistant toward the formation of dimers. The capacity of the two stabilized variants of wild type cystatin C to form amyloid fibrils was investigated and found to be reduced by 80% compared with that of wild type cystatin C. In an effort to investigate whether exogenous agents could also suppress the formation of dimers of wild type and L68Q cystatin C, a monoclonal antibody or carboxymethylpapain, an inactivated form of a cysteine protease, was added to systems inducing dimerization of wild type and L68Q cystatin C. It was observed that catalytic amounts of both the monoclonal antibody and carboxymethylpapain could suppress dimerization.

Amyloid↗
PubMed1979

Intravascular endothelial proliferations in children.

Six children who had benign cutaneous vascular lesions characterized by papillary or solid proliferation of the endothelial cells were seen in a 16-year period. In five of them, the lesions had the histologic features of the entity originally described by Masson and recently reported by Clearkin and Enzinger as intravascular papillary endothelial hyperplasia. In one of the five, the lesion appeared in the pure form within large vascular spaces, whereas in the remaining four it appeared as a very limited focal change in a hematoma. The authors agree with others that this lesion represents a peculiar variant of an organizing thrombus. The histologic features of the lesion in the sixth patient were compatible with the so-called "intravenous atypical vascular proliferation," another pseudomalignant vascular disorder recently described by Rosai and Akerman.

Capillaries↗
PubMed2025

Panaln: indexing pangenome for read alignment.

MOTIVATION: Pangenome indexing is a critical supporting technology in biological sequence analysis such as read alignment applications. The need to accurately identify billions of small sequencing fragments carrying sequencing errors and genomic variants drives the development of scalable and efficient pangenome indexing approach. RESULTS: We propose a new wavelet tree-based approach, called Panaln, for indexing pangenome and introduce a batch computation approach for fast count query over Panaln. We present a simple and effective seeding strategy and develop a pangenome program that uses the seed-and-extend paradigm for read alignment. Experimental results on simulated and real data demonstrate that Panaln uses significantly less space for the compared pangenome methods with generally higher accuracy. We provide a scalable index construction by representing pangenome with a linear model. Additionally, Panaln brings enhanced accuracy compared to the popular single reference methods. AVAILABILITY AND IMPLEMENTATION: Package: https://anaconda.org/bioconda/panaln and source code: https://github.com/Lilu-guo/Panaln.

Software↗
PubMed1986

Evidence for neural origin and PAS-positive variants of the malignant small cell tumor of thoracopulmonary region ("Askin tumor").

The differential diagnoses of childhood and adolescent tumors composed of small round cells include a distinctive clinicopathological entity called malignant small cell tumor (MSCT) of the thoracopulmonary region in childhood. In the present study, 15 such tumors that fulfilled the criteria by Askin et al. were examined for features of possible neural differentiation by light and electron microscopy (EM). With hematoxylin-eosin stain (H&E) the tumors were made up of small undifferentiated cells; rosette formation was noticed in four cases. By immunohistochemistry all 15 tumors were positive for neuron/specific enolase (NSE), which is a specific marker for neural elements and their tumors including neuroblastomas. Ten of 15 MSCT had positive PAS staining. Ultrastructurally dense core (neurosecretory) granules and cell processes indicative of neuronal differentiation could be recognized in 10 of 14 tumors. The dense core granules were often atypical. Filamentous cytoskeleton, never observed in Ewing's sarcoma, was often present. Based on the current results, MSCT of the thoracopulmonary region can be considered a peripheral neuroectodermal tumor with the possible origin in intercostal nerves. MSCTs are generally misdiagnosed as Ewing's sarcoma due to their primitive appearance in H&E sections and their periodic acid-Schiff positivity. NSE immunostaining, preferably augmented by electron microscopy, is necessary for their correct diagnosis.

Adolescent↗
PubMed1988

Histology of the anal canal.

The normal gross and microscopic morphology of the anal canal is described, including the more common variants. Constant problems in the literature are the confusing terminology and the relation of the histological zones to the so-called cloacal membrane. For this reason, the review includes remarks on the history, embryology, and nomenclature.

Anal Canal↗
PubMed1996

Length changes in the joining segment between domains 5 and 6 of a group II intron inhibit self-splicing and alter 3' splice site selection.

Domain 5 (D5) and domain 6 (D6) are adjacent folded hairpin substructures of self-splicing group II introns that appear to interact within the active ribozyme. Here we describe the effects of changing the length of the 3-nucleotide segment joining D5 to D6 [called J(56)3] on the splicing reactions of intron 5 gamma of the COXI gene of yeast mitochondrial DNA. Shortened variants J(56)0 and J(56)1 were defective in vitro for branching, and the second splicing step was performed inefficiently and inaccurately. The lengthened variant J(56)5 had a milder defect-splicing occurred at a reduced rate but with correct branching and a mostly accurate 3' splice junction choice. Yeast mitochondria were transformed with the J(56)5 allele, and the resulting yeast strain was respiration deficient because of ineffective aI5 gamma splicing. Respiration-competent revertants were recovered, and in one type a single joiner nucleotide was deleted while in the other type a nucleotide of D6 was deleted. Although these revertants still showed partial splicing blocks in vivo and in vitro, including a substantial defect in the second step of splicing, both spliced accurately in vivo. These results establish that a 3-nucleotide J(56) is optimal for this intron, especially for the accuracy of 3' splice junction selection, and indicate that D5 and D6 are probably not coaxially stacked.

Base Sequence↗