Breast cancer screening using small-angle X-ray scattering analysis of human hair.
Explore the source record for details and available documents.
Breast Neoplasms↗
Biomedical subjects
P Meyer
Publications and source records attributed to P Meyer.
The human nm23-H4 gene product is a mitochondrial nucleoside diphosphate kinase.
We demonstrate here the catalytic activity and subcellular localization of the Nm23-H4 protein, product of nm23-H4, a new member of the human nm23/nucleoside diphosphate (NDP) kinase gene family (Milon, L., Rousseau-Merck, M., Munier, A., Erent, M., Lascu, I., Capeau, J., and Lacombe, M. L. (1997) Hum. Genet. 99, 550-557). Nm3-H4 was synthesized in escherichia coli as the full-length protein and as a truncated form missing the N-terminal extension characteristic of mitochondrial targeting. The truncated form possesses NDP kinase activity, whereas the full-length protein is inactive, suggesting that the extension prevents enzyme folding and/or activity. X-ray crystallographic analysis was performed on active truncated Nm23-H4. Like other eukaryotic NDP kinases, it is a hexamer. Nm23-H4 naturally possesses a serine residue at position 129, equivalent to the K-pn mutation of the Drosophila NDP kinase. The x-ray structure shows that the presence of Ser(129) has local structural effects that weaken subunit interactions. Site-directed mutagenesis shows that the serine is responsible for the lability of Nm23-H4 to heat and urea treatment, because the S129P mutant is greatly stabilized. Examination of human embryonic kidney 293 cells transfected with green fluorescent protein fusions by confocal microscopy shows a specific mitochondrial localization of Nm23-H4 that was also demonstrated by Western blot analysis of subcellular fractions of these cells. Import into mitochondria is accompanied by cleavage of the N-terminal extension that results in NDP kinase activity. Submitochondrial fractionation indicates that Nm23-H4 is associated with mitochondrial membranes, possibly to the contact sites between the outer and inner membranes.
Base Sequence↗
Decreased striatal monoaminergic terminals in Huntington disease.
OBJECTIVE: To evaluate the integrity of the dorsal striatal dopaminergic innervation in rigid and choreic Huntington disease (HD). BACKGROUND: Some patients with HD have an akinetic-rigid phenotype. It has been suggested that nigrostriatal in addition to striatal pathology is present in this subgroup. The authors sought to determine whether in vivo measures of striatal vesicular monoamine transporter type-2 (VMAT2) binding could distinguish patients with akinetic-rigid (HDr) from typical choreiform (HDc) HD. METHODS: Nineteen patients with HD (mean age 48 +/- 16 years) and 64 normal controls (mean age 50 +/- 14 years) underwent (+)-alpha-[11C]dihydrotetrabenazine (DTBZ) PET imaging. DTBZ blood to brain ligand transport (K1) and tissue to plasma distribution volume (DV) in the caudate nucleus, anterior putamen, and posterior putamen were normalized to the occipital cortex. RESULTS: The normalized striatal specific DV was reduced in HDr (n = 6) when compared with controls: caudate nucleus -33% (p < 0.001), anterior putamen -56% (p < 0.0001), and posterior putamen -75% (p < 0.0001). Patients with HDc (n = 13) also had reduced striatal DV: caudate nucleus -6% (NS), anterior putamen -19% (p < 0.01), and posterior putamen -35% (p < 0.0001). Patients with HDr had significantly lower striatal (+)-alpha-[11C]DTBZ binding than HDc patients. After correction for tissue atrophy effects, normalized DV differences were less significant, with values somewhat increased in the caudate, slightly reduced in the anterior putamen, and moderately decreased in the posterior putamen. There were no significant regional differences in K1 reductions among caudate, anterior, and posterior putamen in HD. CONCLUSIONS: Reduced striatal VMAT2 binding suggests nigrostriatal pathology in HD, most severely in the HDr phenotype. Striatal DV reductions were most prominent in the posterior putamen, similar to PD.
Adult↗
The respective contributions of the mother and daughter centrioles to centrosome activity and behavior in vertebrate cells.
We have generated several stable cell lines expressing GFP-labeled centrin. This fusion protein becomes concentrated in the lumen of both centrioles, making them clearly visible in the living cell. Time-lapse fluorescence microscopy reveals that the centriole pair inherited after mitosis splits during or just after telophase. At this time the mother centriole remains near the cell center while the daughter migrates extensively throughout the cytoplasm. This differential behavior is not related to the presence of a nucleus because it is also observed in enucleated cells. The characteristic motions of the daughter centriole persist in the absence of microtubules (Mts). or actin, but are arrested when both Mts and actin filaments are disrupted. As the centrioles replicate at the G1/S transition the movements exhibited by the original daughter become progressively attenuated, and by the onset of mitosis its behavior is indistinguishable from that of the mother centriole. While both centrioles possess associated gamma-tubulin, and nucleate similar number of Mts in Mt repolymerization experiments. during G1 and S only the mother centriole is located at the focus of the Mt array. A model, based on differences in Mt anchoring and release by the mother and daughter centrioles, is proposed to explain these results.
3T3 Cells↗
Increasing the number of hepatitis B vaccine injections augments anti-HBs response rate in HIV-infected patients. Effects on HIV-1 viral load.
Preventing hepatitis B by vaccination is essential in HIV-infected patients (higher progression rate of HBV infection to chronicity, lower rate of serum HBe Ag loss). However, it has been shown a decreased anti-HBs response in these individuals after a standard vaccination (3 doses of 20 micrograms). Thus, we tested the hypothesis that doubling the number of hepatitis B vaccine injections might increase anti-HBs response rate. HIV-infected patients with CD4 > 200/microliter, who were on stable antiretroviral treatment, as well as seronegative for HBV markers, and who have never been vaccinated against HBV, were given 3 intramuscular injections of Genhevac B 20 micrograms at 1 month intervals. Initial non responders were given 3 additional monthly injections. Anti-HBs titer was followed. We also evaluated the effects on HIV-1 viral load. Twenty patients with a median CD4 cell count of 470/microliter were enrolled. The response rate after three 20 micrograms injections was 55% (11/20), lower in individuals with CD4 between 200 and 500/microliter (4/12 = 33.3%), compared to patients with CD4 above 500/microliter (7/8 = 87.5%, P = 0.02). Among 9 initial non-responders, only 2 did not respond to 3 additional doses; thus, the overall response rate was 90% (18/20). Geometric mean titers of anti-HBs were 133 IU/l and 77.5 IU/l, after 3 and 6 Genhevac doses, respectively (P = 0.38). One year later, only 10/17 (58.8%) patients had protective anti-HBs. Five patients experienced a significant viral load increase, transient in 3 cases. These preliminary results suggest that doubling the number of hepatitis B vaccinations in HIV-infected patients might significantly improve anti-HBs response rate; however, close monitoring of anti-HBs is necessary because of its short-lived persistence. The effects on HIV-1 viral load are limited.
Adult↗
123I-antileukoproteinase scintigraphy reveals microscopic cartilage alterations in the contralateral knee joint of rats with "monarticular" antigen-induced arthritis.
OBJECTIVE: To assess the involvement of the contralateral knee joint in monarticular antigen-induced arthritis (AIA) by scintigraphy with the cationic (pI >10), 123I-labeled, serine proteinase inhibitor antileukoproteinase (123I-ALP) and to compare the scintigraphic findings with those of radiography and high-resolution ex vivo magnetic resonance imaging (MRI). METHODS: Lewis rats with chronic AIA were examined 2.5 months following arthritis induction (injection of 500 microg of methylated bovine serum albumin/saline into the ipsilateral [arthritic] knee joint and injection of phosphate buffered saline into the contralateral knee joint following systemic immunization). 123I-ALP was injected intravenously into normal rats (n = 4) or rats with AIA (n = 6). The ipsilateral and contralateral knee joints and both ankles were examined by scintigraphy and radiography. Joint cartilage was examined by high-resolution ex vivo MRI, histopathology, and measurement of tissue radioactivity. RESULTS: ALP accumulation (typically observed in normal articular cartilage) was lost in both the ipsilateral and the contralateral knee joints, but not in the clinically unaffected ankles of rats with AIA. In both knee joints, 123I-ALP target:background ratios and cartilage radioactivity correlated negatively with the loss of toluidine blue staining in cartilage, which documents the depletion of charged matrix molecules. Findings of histopathology confirmed mild alterations in the ipsilateral knee joint and even milder alterations in the contralateral knee joint, while the ankles were normal. Radiography and high-resolution ex vivo MRI failed to detect abnormalities in the contralateral knee joint. CONCLUSION: Loss of ALP accumulation appears to document proteoglycan depletion, even in the microscopically altered cartilage of the contralateral knee joint in AIA. These findings underscore the high sensitivity of 123I-ALP for in vivo detection of biochemical cartilage alterations in arthritis, and furthermore, question the use of the contralateral knee joint as a normal control in AIA.
Animals↗
Rare presentation of actinomycosis as an abdominal mass: report of a case.
PURPOSE: The purpose of this article was to report an unusual presentation of abdominal actinomycosis masquerading as a tumor. METHODS: The patient was a 54-year-old male who presented with vague abdominal discomfort and a palpable left lower quadrant mass defined on CT scan. Multiple intraoperative core biopsies were nondiagnostic, and he underwent en bloc resection of the mass and adjacent organs for a presumed tumor. RESULTS: Examination of tissue from deep within the excised specimen revealed sulfur granules diagnostic for actinomycosis. CONCLUSION: Abdominal actinomycosis is an extremely rare infection that can mimic multiple disease processes and requires accurate diagnosis for successful therapy. This novel presentation and a review of the literature are reported.
Abdomen↗
Regulation of connective tissue growth factor gene expression in retinal vascular endothelial cells by angiogenic growth factors.
BACKGROUND: Connective tissue growth factor (CTGF) is a novel, cysteine-rich secreted protein, which is implicated in fibrotic disorders and atherosclerosis. To elucidate the role of CTGF in fibrovascular proliferative retinopathy, we investigated the regulation of CTGF gene expression in a cell line of retinal vascular endothelial cells (RVEC) stimulated with fetal calf serum (FCS) and angiogenic growth factors, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor-BB (PDGF-BB), endothelial growth factor (EGF), transforming growth factor-beta 1 and -beta 3 (TGF-beta 1, TGF-beta 3), and insulin-like growth factor-I (IGF-I). METHODS: RVEC derived from Macaca mulatta (CRL-1780; ATCC) were stimulated with 10% FCS as well as with VEGF, bFGF, PDGF-BB, TGF-beta 1, TGF-beta 3, EGF, or IGF-I. Time-dependent CTGF gene expression was assessed by northern blot analysis. RESULTS: FCS, TGF-beta 1, TGF-beta 3, bFGF, and EGF induced an upregulation of CTGF gene expression in RVEC in a time-dependent manner. Highest expression was induced with TGF-beta 1. No response on CTGF gene expression could be detected to VEGF, PDGF-BB, or IGF-I. CONCLUSION: The present study demonstrates for the first time that CTGF mRNA is expressed at high levels in RVEC, and that the level of the temporal pattern of its expression is differentially regulated by angiogenic growth factors, indicating a significant role of CTGF in the pathological course of uncontrolled retinal angiogenesis.
Animals↗
High prevalence of GB virus C/hepatitis G virus RNA and antibodies in patients infected with human immunodeficiency virus type 1.
The prevalence of GB virus C (GBV-C)/ hepatitis G virus (HGV) RNA and antibodies to the structural E2 protein was investigated in a cohort of HIV-1 infected patients. Of 346 individuals, RNA was detected in 143 and E2 antibodies were detected in 73, for an overall prevalence of 62.4%. Intravenous drug use and homosexuality were identified as major transmission risk factors. GBV-C/HGV RNA prevalence was associated with hepatitis B coinfection, whereas antibodies to E2 were associated with older age and lower CD4+ cell counts. GBV-C/HGV infection was frequent in this group of HIV-infected patients and was associated with older age, lower CD4 + cell counts, and the presence of hepatitis B surface antigen.
Adenovirus E2 Proteins↗
Poor prognosis acute myelogenous leukemia 2--biological and molecular biological characteristics and treatment outcome.
Biological and molecular biological studies were performed on the marrow cells of 25 patients with poor prognosis AML to both characterize this type of leukemia and to assess the relationship between the parameters which were measured and treatment outcome. Treatment failure associated with high levels of telomerase activity and low levels of IL6 transcripts. Studies of the effects of amifostine on these parameters demonstrated that this agent reduced telomerase activity in aspirates of AML marrows. These data suggest that the beneficial effect associated with the administration of amifostine after the end of chemotherapy is likely, to be due to a reduction in the rate at which the surviving leukemia cells repopulate the marrow.
Amifostine↗
[Effect of a lung contusion on the prognosis of severe head injury in the child].
OBJECTIVES: To assess the effects of a pulmonary contusion (PC) on the outcome of a severe head trauma (SHT) in children less than 15-year-old. STUDY DESIGN: Retrospective study. PATIENTS: The study included 30 severely head injured children with a Glasgow Coma Scale score (GCS) < or = 8, associated with a PC (PC+) diagnosed on a thoracic CT-scan and 30 severely head injured children without PC (PC-). METHODS: Outcome was assessed using the Glasgow Outcome Scale (GOS), on discharge and six months later. Age, body weight, gender, GCS, PTS, ISS, hypoxaemia, arterial hypotension, the results of the cerebral CT-scan, the main treatment administered, complications, the duration of tracheal intubation as well as the duration of stay in the intensive care unit (ICU) and in the hospital were compared between groups. RESULTS: GCS median was lower (6 vs 8, P = 0.001) and ISS median higher (25 vs 23, P = 0.0004) in the PC+ group. Hypoxaemia was more frequent in the PC+ group (n = 12 vs n = 0, P = 0.0001). There was no difference between groups regarding the results of cerebral CT scan. Blood transfusion was more frequently used in the PC+ group (n = 14 vs n = 5, P = 0.03). Median duration of tracheal intubation, and of stay in the ICU and in the hospital were shorter in the PC- group (respectively 8 vs 6 days, P = 0.03; 10 vs 7.5 days, P = 0.008; 13.5 vs 10.5 days, P = 0.01). No difference was observed regarding complications between groups. GOS on discharge was higher in the PC+ group (3 vs 2, P = 0.01). There was an increase in GOS at six months in the two groups, however GOS remained significantly higher in the PC+ group (median values 2 vs 1, P = 0.002). A favourable outcome occurred less frequently in the PC+ group on discharge and at six months (respectively n = 14 vs 25, P = 0.006; n = 20 vs 28, P = 0.02). CONCLUSION: The association of a PC to a severe head trauma is responsible for a poorer outcome in children, probably because, at least in part, a higher incidence of hypoxaemia.
Adolescent↗
Clinical, microbiological and pathological observations in laboratory beagle dogs infected with leptospires of the serogroup Sejroe.
In beagle dogs infections with two different serovars of serogroup Sejroe are described. Saxkoebing titres of 27 beagle dogs were controlled for 7 to 9 months. Dogs serologically positive for saxkoebing showed no clinical symptoms. From the urine, an isolation of the microorganisms was possible. At necropsy, there was no evidence of any changes related to the proven infection. Histopathologically, in animals with persistent titres a mild interstitial nephritis was found. No changes were observed in the liver. Another three beagle dogs died after about two days of acute clinical illness with febrile temperature, exsiccosis and hematuria. Histopathologically, incipient inflammation was seen in the liver and kidneys. Besides, hepatic cholestasis, renal hemoglobin casts and degeneration of renal tubular epithelia were observed. In concurrent animals, an infection with another serovar of serogroup Sejroe was proven serologically. This serovar was also isolated. Transmission and spreading of leptospirosis within animals shelters or laboratories from clinically healthy carriers and its prevention as well as the protection of animal caretakers are discussed. Since leptospires are sensitive to physical and chemical methods of disinfection, this is easily feasible. However, the optimal prevention appears to be a stock- or population-specific vaccination.
Animals↗
Three-dimensional structure of nucleoside diphosphate kinase.
Three-dimensional structures are known from X-ray studies of the nucleoside diphosphate (NDP) kinase of many organisms from bacteria to human. All NDP kinases have subunits of about 150 residues with a very similar fold based on the alphabeta sandwich or ferredoxin fold. This fold is found in many nucleotide or polynucleotide-binding proteins with no sequence relationship to NDP kinase. This common fold is augmented here with specific features: a surface alpha-helix hairpin, the Kpn loop, and the C-terminal extension. The alpha-helix hairpin and Kpn loop make up the nucleotide binding site, which is unique to NDP kinase and different from that of other kinases or ATPases. The Kpn loop and the C-terminal extension are also involved in the quaternary structure. Whereas all known eukaryotic NDP kinases, including mitochondral enzymes, are hexamers, some bacterial enzymes are tetramers. However, hexameric and tetrameric NDP kinases are built from the same dimer. The structural environment of the active histidine is identical in all. The nucleotide binding site is also fully conserved, except for a feature implicating C-terminal residues in the hexamer, but not in the tetramer. Structural data on the native and phosphorylated enzyme, complexes with substrates, inhibitor, and a transition state analog, give a solid basis to a mechanism of phosphate transfer in which the largest contributors to catalysis are the 3'-OH of the sugar and the bound Mg2+ in the nucleotide substrate. In contrast, we still lack structural data relating to DNA binding and other functions of NDP kinases.
Animals↗
Transcriptional transgene silencing and chromatin components.
Contrary to simplistic views that have long prevailed in genetics textbooks, gene transcription in higher organisms cannot be fully understood by analysing binding of transcription factors to DNA target sites within the promoter regions, just as it would be inappropriate to picture the genetic information within a nucleus as a simple string of DNA. Instead, DNA is embedded in a highly complex chromatin structure that controls the location and accessibility of individual genetic regions in a way we are still far from understanding in detail. What has become obvious, mainly due to ground-breaking research in yeast and animal systems, is that the packaging of certain genes into a chromosomal matrix is regulated via sophisticated chromatin remodelling mechanisms that define whether and when a gene becomes accessible to the transcription machinery. In plants, especially the analysis of transgenes and transposable elements has reminded us of the presence of epigenetic control mechanisms, which can affect the reliable expression of transgenes. There is increasing evidence that chromatin components play an important part in plant epigenetics. The purpose of this review is to describe the main general principles of chromatin remodelling as they have been elucidated in non-plant systems and to discuss their relevance for the control of gene expression in plants.
Chromatin↗
Intrachromosomal recombination between attP regions as a tool to remove selectable marker genes from tobacco transgenes.
Recombinant genes conferring resistance to antibiotics or herbicides are widely used as selectable markers in plant transformation. Once transgenic material has been selected, the marker gene is dispensable. We report a novel strategy to remove undesirable parts of a transgene after integration into the tobacco genome. This approach is based on the transfer of a vector containing a NPTII gene flanked by two 352 bp attachment P (attP) regions of bacteriophage lambda, and the identification of somatic tissue with deletion events following intrachromosomal recombination between the attP regions. This system was used to delete a 5.9 kb region from a recombinant vector that had been inserted into two different genomic regions. As the attP system does not require the expression of helper proteins to induce deletion events, or a genetic segregation step to remove recombinase genes, it should provide a useful tool to remove undesirable transgene regions, especially in vegetatively propagated species.
Bacteriophage lambda↗
[Ganglioglioma of optic nerve in neurofibromatosis type 1. Case report and review of the literature].
BACKGROUND: Gangliogliomas are rare tumors of the central nervous system. In only seven cases they have been found within the optic nerve. Two of these cases were associated with neurofibromatosis (NF), but a pathogenic link between gangliogliomas of the optic nerve and NF still remains controversial. PATIENT: Here we report on a 71-year-old patient with a ganglioglioma of the optic nerves and NF type 1. Post mortem examination revealed multiple neurofibromas of the vagal and left femoral nerves, multiple schwannomas of the small bowel and Lisch noduli of both irides. In addition, a spindle shaped thickening of the right optic nerve was observed in its intracranial portion. The left optic nerve was normal on gross inspection. RESULT: Histologically, tumoral tissue was found in both optic nerves. The tumor was composed of two cell types: highly differentiated, partly stellate, partly pilocytic astrocytes and, at the rim of the axon bundles of the optic nerve, fully developed synaptophysin- and neurofilament-antigen-positive ganglion-cells with short corkscrew-shaped processes. No mitosis could be found in the neuronal or in the glial cell population. In spite of the tumoral involvement of the optic nerves, there has been no evidence of visual disturbance. CONCLUSION: Optic nerve tumors in NF most often are of glial origin (astrocytomas, pilocytic astrocytomas). Our case illustrates the rare condition of a glioneuronal tumor associated with neurofibromatosis type 1.
Aged↗
Campath-1H therapy in refractory ocular inflammatory disease.
BACKGROUND: Standard therapy for severe, immune mediated, ocular inflammation has significant side effects, and may fail to control the disease. T cell directed monoclonal antibody (mAb) therapy can provide long term remission of inflammatory disease in experimental models. The Campath-1H mAb was administered to patients with severe, refractory, ocular inflammation. METHODS: 10 patients with severe, refractory, non-infectious ocular inflammatory disease were treated with Campath-1H mAb. This is a fully humanised mAb which recognises the pan-lymphocyte antigen CD52. RESULTS AND DISCUSSION: Following Campath-1H therapy, all 10 patients showed an initial resolution of their ocular symptoms and signs. Long lasting remissions were achieved in eight patients, in whom baseline immunosuppression could subsequently be reduced to minimal levels. The possible mechanisms of action of Campath-1H therapy are discussed.
Adult↗
Telepathology: design of a modular system.
Although telepathology systems have been developed for more than a decade, they are still not a widespread tool for routine diagnostic applications. Lacking interoperability, software that is not satisfying user needs as well as high costs have been identified as reasons. In this paper we would like to demonstrate that with a clear separation of the tasks required for a telepathology application, telepathology systems can be built in a modular way, where many modules can be implemented using standard software components. With such a modular design, systems can be easily adapted to changing user needs and new technological developments and it is easier to integrate modular systems into existing environments.
Computer Systems↗