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At least 793 records · Page 44Linked to original sources
PubMed1991

Study of calcitonin and thyroglobulin gene expression in human mixed follicular and medullary thyroid carcinoma.

mRNAs were isolated from 2 patients suffering from a familial form of a rare variant of medullary carcinoma of the thyroid (MTC), called mixed follicular and medullary carcinoma. The presence of calcitonin (CT) and thyroglobulin (Tg) mRNAs was checked by northern and in situ hybridization and compared with immunohistochemical results. In each case, mRNAs hybridizing to probes specific for CT and Tg were detected. Both proteins were quantified by radioimmunoassay determination in tissue extracts. Patient 1 had 20 ng Tg and 68 ng CT per micrograms total protein, and patient 2 had 0.4 ng Tg and 1.7 ng CT per micrograms total protein. Northern analysis showed that mixed carcinoma expressed several species of both CT mRNAs and Tg mRNAs. The main Tg transcripts present in neoplastic cells (8.5 and 4.8 kb for patient 1 and patient 2) were identical to or smaller than those of normal thyroid tissue (8.5 kb). The tumor CT mRNA (1 kb) was identical to that of normal tissue. In situ hybridization confirmed the presence of CT and Tg mRNA in the great majority of tumor cells. Furthermore, the presence of small amounts of organified iodine was evidenced by analytical ion microscopy in 35% of these cells. This raises an important question regarding the histogenesis of this tumor.

Adenocarcinoma↗
PubMed1998

Immune escape mechanisms in Hodgkin's disease.

BACKGROUND: The nodular sclerosis and mixed cellularity subtypes of Hodgkin's disease are histologically characterised by a small population of neoplastic cells, the so-called Reed-Sternberg cells and their mononuclear variants (RS cells) and an extensive admixture of other cell types including lymphocytes, plasma cells, eosinophils, and histiocytes. The nature of this infiltrate is largely known, but the mechanisms and functional effects are not. The small lymphocytes immediately surrounding the RS cells are mostly CD4+ T cells that express early activation markers. The absence of prominent specific cytotoxic T cell or natural killer (NK) cell populations seems to argue against a Th1-type response, whereas the sometimes prominent admixture of plasma cells and eosinophils is suggestive of a Th2-type response. Enrichment of the CD4 T-cell population may result from selective influx of CD4 T cells or from selective depletion of CD8 and NK cells. RESULTS AND DISCUSSION: The T cells surrounding RS cells have an immuno-phenotype and cytokine production capability consistent with a Th2-type response. RS cells express several members of the TNF receptor family such as the FAS ligand (CD95L) that may induce apoptosis of activated, FAS expressing, CD8+ T cells and NK cells. The RS cells also produce TGF beta and interleukin-10 that may downmodulate the Th1 response. In addition, the Reed-Sternberg cells produce the chemokine TARC that could lead to the specific attraction of a Th2 T-cell subset. CONCLUSION: RS cells have several mechanisms that may allow it to escape an effective immune response. The relative contributions of each of these and other potential mechanisms are not yet known.

CD4 Antigens↗
PubMed1979

Hodgkin's disease with lymphocytic predominance, nodular type (nodular paragranuloma) and progressively transformed germinal centres--a cytohistological study.

The histology, cytology, and enzyme cytochemistry of a nodular variant of Hodgkin's disease with lymphocytic predominance, called 'nodular paragranuloma', are presented. The histological features of nodular paragranuloma are compared with those of progressively transformed germinal centres, which are enlarged follicles showing a predominance of small lymphocytes and some residual germinal centre cells. Progressively transformed germinal centres are sometimes found in nonspecific lymphadenitis (reactive hyperplasia). The histological similarity and the association between lymph nodes with nodular paragranuloma and lymph nodes with progressively transformed germinal centres in the same patient at different moments or at the same time, suggest that progressively transformed germinal centres are the origin of nodular paragranuloma. Hence, it must be concluded that nodular paragranuloma takes place in B-cell areas of the lymph node, unlike the other, or at least most of the other, types of Hodgkin's disease.

Adult↗
PubMed1994

Horizontal gene transfer in the evolution of group A streptococcal emm-like genes: gene mosaics and variation in Vir regulons.

Most M type 5 group A streptococcal strains were found to contain a single emm-like gene between virR and scpA (the Vir regulon), but two distinct emm-like genes were identified in the Vir regulon of the M5 strain NCTC8193. The complete sequences of both of these genes were determined. One, called emm5.8193, was shown to be a minor variant of the previously described emm5 gene from strain Manfredo. The second, designated enn5.8193, expresses an IgG-binding protein when cloned in Escherichia coli. A comparison of enn5.8193 with emm-like gene sequences from other strains indicated that it has a mosaic structure, consisting of distinct segments originating from emm-like genes in different OF+ and OF- strains. These data provide the first clear evidence that the horizontal transfer of emm-like sequences between distinct strains contributes to the evolution of group A streptococcal emm-like genes and Vir regulons.

Bacterial Proteins↗
PubMedDate not supplied

A cooperative conformational change in duplex DNA induced by Zn2+ and other divalent metal ions.

Zn2+ and some other divalent metal ions bind to duplex DNA at pHs above 8 and cause a conformational change. This new structure does not bind ethidium, allowing the development of a rapid fluorescence assay. All duplex DNAs, regardless of sequence or G.C content, can form this structure. The rate of formation shows a strong dependence on temperature, pH, and Zn2+ concentration; at 20 degrees C, 1 mM Zn2+, and pH 8.6 the dismutation is half complete in 30 min. Addition of EDTA causes rapid reversion to 'B' DNA, showing that the new conformation retains two strands that are antiparallel. Unlike the ultraviolet or circular dichroism spectra, the nuclear magnetic resonance spectrum was informative since the imino protons of both A.T and G.C base pairs are lost upon addition of a stoichiometric amount of Zn2+. The pitch of the helix was estimated from gel electrophoresis of circular DNAs in the presence of Zn2+ and it contains at least 5% fewer base pairs per turn than 'B' DNA. The transformation is cooperative and shows hysteresis, suggesting that this is a distinct structure and not simply a minor variant of 'B' DNA. It is proposed to call this new structure 'M' DNA because of the intimate involvement of metal ions.

Circular Dichroism↗
PubMed1996

Two receptor interacting domains in the nuclear hormone receptor corepressor RIP13/N-CoR.

The thyroid hormone receptor (TR) and the retinoic acid receptor (RAR) act as transcriptional repressors when they are not occupied by their cognate ligands. This repressor function is mediated by proteins called corepressors. One of the nuclear hormone receptor corepressors, N-CoR, was originally isolated as a retinoid X receptor-interacting protein called RIP13. We have isolated a new potential variant of RIP13/N-CoR that is missing previously described transcriptional repressor domains but is similar in structure to the related corepressor termed SMRT or TRAC-2. Detailed analysis of the interaction with TR and RAR demonstrates that RIP13/N-CoR contains a new receptor interaction domain, termed ID-II, in addition to the previously described domain, referred to here as ID-I. Both ID-I and ID-II are capable of interacting independently with either TR or RAR, as assessed by the yeast two-hybrid system, by a mammalian two-hybrid system, or by direct in vitro binding. Results with all three approaches confirm that RIP13/N-CoR also interacts with retinoid X receptor, but this interaction is weaker than that with TR or RAR. Together, these results demonstrate that RIP13/N-CoR can interact with several different nuclear hormone receptors via two separate receptor interaction domains. Differences between the interactions observed in the different systems suggest that corepressor function may be modified by additional factors present in various cell types.

Amino Acid Sequence↗
PubMed2002

Oral lichenoid drug eruptions: their recognition and management.

Lichen planus is a relatively common, often clinically distinctive, mucocutaneous condition with an uncertain aetiology. One variant of lichen planus is the so-called 'lichenoid drug eruption'. In contrast to idiopathic lichen planus, lichenoid drug eruptions, where practicable, may be managed by substitution of the offending drug. The dental clinician is in a prime position to identify these lesions and liaise with medical colleagues regarding their management. This article reviews oral lichenoid drug eruptions, emphasizing those aspects of relevance to the general dental practitioner.

Adult↗
PubMed2006

A cost-effective melting temperature assay for the detection of single-nucleotide polymorphism in the MBL2 gene of HIV-1-infected children.

We report a fast (less than 3 h) and cost-effective melting temperature assay method for the detection of single-nucleotide polymorphisms in the MBL2 gene. The protocol, which is based on the Corbett Rotor Gene real time PCR platform and SYBR Green I chemistry, yielded, in the cohorts studied, sensitive (100%) and specific (100%) PCR amplification without the use of costly fluorophore-labeled probes or post-PCR manipulation. At the end of the PCR, the dissociation protocol included a slow heating from 60 degrees to 95 degrees C in 0.2 degrees C steps, with an 8-s interval between steps. Melting curve profiles were obtained using the dissociation software of the Rotor Gene-3000 apparatus. Samples were analyzed in duplicate and in different PCR runs to test the reproducibility of this technique. No supplementary data handling is required to determine the MBL2 genotype. MBL2 genotyping performed on a cohort of 164 HIV-1-positive Brazilian children and 150 healthy controls, matched for age and sex and ethnic origin, yielded reproducible results confirmed by direct sequencing of the amplicon performed in blind. The three MBL2 variants (Arg52Cys, Gly54Asp, Gly57Glu) were grouped together and called allele 0, while the combination of three wild-type alleles was called allele A. The frequency of the A/A homozygotes was significantly higher among healthy controls (0.68) than in HIV-infected children (0.55; P = 0.0234) and the frequency of MBL2 0/0 homozygotes was higher among HIV-1-infected children than healthy controls (P = 0.0296). The 0 allele was significantly more frequent among the 164 HIV-1-infected children (0.29) than among the 150 healthy controls (0.18; P = 0.0032). Our data confirm the association between the presence of the mutated MBL2 allele (allele 0) and HIV-1 infection in perinatally exposed children. Our results are in agreement with the literature data which indicate that the presence of the allele 0 confers a relative risk of 1.37 for HIV-1 infection through vertical transmission.

Case-Control Studies↗
PubMed2002

Evaluation of current approaches to inhibit HIV entry.

Highly active inhibitors of human immunodeficiency virus (HIV) reverse transcriptase and protease have made it possible to dramatically reduce virus load in HIV-positive individuals. However, the presence of viral reservoirs, the emergence of drug-resistant HIV variants and the side effects of these compounds call for research into new drugs that target different stages of the viral life cycle. One attractive target is the first step in HIV replication: entry of virus into cells. HIV entry is initiated by the attachment of the virus to the host cell membrane, which is some cases involves binding to attachment factors such as DC-SIGN. Subsequent interaction of the envelope protein (Env) with the CD4 receptor causes conformational changes that enable Env to interact with a coreceptor, generally the chemokine receptors CCR5 or CXCR4. Coreceptor engagement triggers the final conformational changes in Env, which mediate lipid mixing between the viral and cellular membranes. All of these steps are potential targets for therapeutic intervention: targeting proteins that mediate viral attachment may reduce HIV transmission, while receptor blockade will inhibit virus entry. Highly conserved domains in Env which bind to CD4 and coreceptor are promising targets for broadly neutralizing antibodies, and peptide inhibitors that bind to Env and that block membrane fusion are in advanced clinical trials. These new approaches may supplement current HIV therapy and may assist in the development of an HIV vaccine.

Anti-HIV Agents↗
PubMed2000

Apolipoprotein E4: an allele associated with many diseases.

Apolipoprotein E (apoE) was discovered as a plasma protein involved in lipoprotein metabolism. ApoE is synthesized by the liver and is also made locally in the brain. There are three common variants of apoE, resulting from common genetic variation, called E2, E3 and E4. The E3 allele is the most prevalent form, and the proportion of the three alleles differs between populations. Epidemiological studies have found that the E4 allele is associated with decreased longevity, increased plasma cholesterol levels and increased prevalence for cardiovascular disease and particularly for Alzheimer's disease. The apoE polymorphism also affects response to head trauma, cognitive decline upon ageing and several other disorders. Thus, common genetic variation in the apoE gene may be associated with successful ageing.

Aging↗
PubMed1998

Multimodal time-variant signal analysis of neonatal EEG burst patterns.

It can be shown that dominant rhythmic signal components of neonatal EEG burst patterns (discontinuous EEG in quiet sleep) are characterized by a quadratic phase coupling (bispectral analysis), i.e. a multiplicative interaction (connection) between the underlying electrophysiological processes can be assumed. By means of pattern recognition algorithms as well as time-variant spectral and coherence analysis, a so-called "initial wave" (narrow band rhythm within a frequency range of 3-12 Hz) can be demonstrated within the first part of the burst pattern. The detection of this signal component and of the quadratic phase coupling is more successful in the frontal region. By means of amplitude demodulation of the "initial wave" the phase coupling can be attributed to an amplitude modulation. The results were derived from 6 neonates (20 burst patterns for each neonate; 8-channel recordings). A 16-channel EEG-recording was analyzed for one neonate.

Electroencephalography↗
PubMedDate not supplied

Advantages of treatment with human follicular fluid in the management of severely dyspermic patients in human in vitro fertilization programs.

In 26 couples undergoing in-vitro fertilization and embryo transfer (IVF/ET), where the male partner was severely dyspermic, the seminal fluid was treated with Pellet Swim-up (PSu), modified by a 20-minute sperm incubation period in non-decomplemented human follicular fluid (hFF) diluted to 50%. In another group of 26 severely dyspermic couples undergoing IVF/ET, the semen was treated with a variant of centrifugation on discontinuous Percoll gradients (CDPG), called mini-CDPG. Pre-treatment with hFF produced a significant increase in oocyte fertilization rate (46.8% in the hFF group compared with 18.4% in the mini-CDPG couples; Kolmogorov-Smirnov Test: D = 0.5, p < 0.01), in the transfer rate per patient (96.1% in the hFF group and 50% in the mini-CDPG group; (Chi-square Test: x2 = 11.827, p < 0.001), and in the pregnancy rate per patient (respectively of 26.9% and 0%; Fisher's exact probability test: P = 0.0049, p < 0.01). There was a high miscarriage rate in the pregnancies obtained in the hFF group (42.8%). The results might be linked to a positive effect of the hFF on sperm capacity and on acrosome reaction. The Authors conclude that the use of hFF would seem to be an extremely useful treatment of the semen of severely dyspermic patients in assisted fertilization programs.

Abortion, Spontaneous↗
PubMedDate not supplied

Galeazzi-equivalent injuries of the wrist in children.

Fracture of the distal radius with dislocation of the distal ulna, the so-called Galeazzi fracture, is uncommon in children. A variant, the "Galeazzi-equivalent fracture" involving a separation of the distal ulnar growth plate with displacement of the ulnar metaphysis was shown to be more common than the "classic" Galeazzi fracture in a 15-year review of this fracture pattern at the Children's Hospital of Eastern Ontario. An analysis of outcome of 10 fractures showed less favorable results in the six Galeazzi-equivalent fractures compared to the four classic Galeazzi injuries, with one child sustaining a complete growth plate arrest of the distal ulna secondary to an equivalent injury. Recognition of the Galeazzi-equivalent fracture pattern is sometimes difficult. To define the various fracture patterns in an attempt to facilitate diagnosis and management, a classification of the Galeazzi injury complex in children has been devised. Reduction of all Galeazzi injury patterns is best accomplished with the forearm in full supination in an above-elbow cast.

Adolescent↗
PubMed1997

[Cutaneous eruptions of streptococcal and staphylococcal origin].

Scarlet fever consists in a diffuse exanthem associated with mucous changes. Classical scarlet fever is rare now, but other severe streptococcal infections have become more frequent, such as streptococcal toxic shock syndrome. The scarlatiniform exanthem and the shock observed in this disease are due to a streptococcal pyrogenic exotoxin. Exfoliative toxins secreted by Staphylococcus aureus are responsible for the tender erythema and cutaneous scaling characteristic of staphylococcal scalded skin syndrome of infancy. The so-called staphylococcal scarlet fever is probably an attenuated variant of this disease. Toxic shock syndrome toxin 1 (TSST1) is another staphylococcal toxin implied in the staphylococcal toxic shock syndrome. This disease is characterized by general symptoms and a scarlatiniform exanthem which are due to the effects of TSST1, acting as a superantigen.

Child↗
PubMed2004

Functional differences between two DCLK splice variants.

Recently, we have cloned two splice variants of the doublecortin-like kinase (DCLK) gene, called DCLK-short-A and -B, both of which encode calcium/calmodulin-dependent protein kinase (CaMK)-like proteins with different C-terminal ends. Using in situ hybridization, we have found that both are highly expressed in limbic structures of the brain and that their expression differs in a number of brain areas. DCLK-short-A is relatively more strongly expressed than DCLK-short-B in the subependymal zone. The DCLK-short-B variant shows stronger expression in the cortex, the ventromedial and dorsomedial hypothalamic nuclei, the arcuate nucleus, the zona incerta and the subincertal nucleus. Also, within the hippocampus, the relative distribution of these two splice variants differs. DCLK-short-B expression compared to DCLK-short-A is highest in the CA1 area. The expression of the A variant is highest in the CA3/CA4 area. Additionally, DCLK-short-B is expressed at a higher level than DCLK-short-A in the substantia nigra and the mammillary nucleus. Both DCLK-short-A and -B were located in the cytoplasm, however DCLK-short-B was also found specifically in growth cone like structures and near the nucleus. Both DCLK-short proteins phosphorylate autocamtide and syntide, two highly specific CaMK substrates. Finally, removal of the C-terminal end of DCLK-short leads to a 10-fold increase of kinase activity, indicating that the different C-termini represent auto-inhibitory domains. Our results indicate that DCLK-short-A and -B control different neuronal processes that overlap with those controlled by CaMKs.

Alternative Splicing↗
PubMed1982

Heterogeneity of "Mediterranean type" glucose-6-phosphate dehydrogenase (G6PD) deficiency in Spain and description of two new variants associated with favism.

Glucose-6-phosphate dehydrogenase (G6PD); EC 1.1.1.49 from thirty-six unrelated Spanish males was partially purified from blood, and the variants were characterized biochemically and electrophoretically according to the methods recommended by the world Health Organization. Subjects were from multiple geographic regions within Spain, and all suffered from hemolytic anemia, either acute (34 cases) or chronic nonspherocytic (2 cases). Almost all the variants studied presented residual erythrocyte G6PD activity ranging from 0 to 10% of normal, and five different mutants were responsible for the deficient phenotype. Three variants were similar to others previously described: G6PD Mediterranean (11 cases), G6PD Athens-like (3 cases), and G6PD Union (2 cases). The remaining variants were different from the numerous variants already reported and have been considered as new mutants. Provisionally they are called G6PD Betica (19 cases) and G6PD Menorca (1 case). The present study constitutes the first attempt to characterize the deficient G6PD variants found in Spain and supplies new data on the relationship between molecular characteristics of deficient variants and their clinical manifestations. The most important findings can be summarized as follows: (1) The Spanish population is characterized by an important heterogeneity in G6PD deficiency. (2) Although G6PD Mediterranean is very frequent, it presents a relatively high degree of polymorphism. (3) Favism has been observed associated with all kinds of variants described here. (4) G6PD Betica, which is the most frequent variant found in subjects of Southern Spanish origin, has been observed associated with favism in all cases except one.

Adolescent↗
PubMed1975

Four new pyruvate kinase (PK) variants and a classical PK deficiency.

Four new red-cell pyruvate kinase (PK) variants are presented along with one case of so-called classical type PK deficiency. PK 'Tokyo II' had a low activity, Km (PEP) and Vmax, but a normal urea stability and only slight deviation from normal in neutralization tests by antiserum. It had a normal nucleotide specificity, abnormal electrophoretic mobility (fast moving) and the variant was associated with a mild hemolytic anaemia. PK 'Maebashi' had a low activity, high Km (PEP), low Vmax, urea instability, decreased reactivity to antiserum, normal electrophoretic mobility, normal nucleotide specificity and was associated with a moderate haemolytic anaemia. PK 'Tsukiji' had low activity, high Km (PEP), markedly high Vmax, urea instability, decreased reactivity to antiserum, abnormal electrophoretic mobility (fast moving) and grossly abnormal nucleotide specificity especially abnormal behaviour to ADP. The haemolytic process in this case was moderate to severe. PK 'Ube' was electrophoretically abnormal (fast moving) but otherwise had normal characteristics and the propositus was healthy and not anaemic. PK 'Ube' was found by electrophoretic screening for genetic PK polymorphism. In the classical type PK deficiency, the usual red-cell PK (PK-R1 and PK-R2) was not demonstrable by electrophoresis but instead M2-type PK was present, presumably by compensatory process. Kinetic studies confirmed that the patient's red-cell PK consisted of M2-type PK. This patient had a severe haemolytic anaemia.

Adult↗
PubMed2005

The degenerate primer design problem: theory and applications.

A PCR primer sequence is called degenerate if some of its positions have several possible bases. The degeneracy of the primer is the number of unique sequence combinations it contains. We study the problem of designing a pair of primers with prescribed degeneracy that match a maximum number of given input sequences. Such problems occur when studying a family of genes that is known only in part, or is known in a related species. We prove that various simplified versions of the problem are hard, show the polynomiality of some restricted cases, and develop approximation algorithms for one variant. Based on these algorithms, we implemented a program called HYDEN for designing highly degenerate primers for a set of genomic sequences. We report on the success of the program in several applications, one of which is an experimental scheme for identifying all human olfactory receptor (OR) genes. In that project, HYDEN was used to design primers with degeneracies up to 10(10) that amplified with high specificity many novel genes of that family, tripling the number of OR genes known at the time.

Algorithms↗