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Biomedical subjects

V Meyer

Publications and source records attributed to V Meyer.

At least 37 records · Page 2Linked to original sources

Experimental entanglement of four particles

Quantum mechanics allows for many-particle wavefunctions that cannot be factorized into a product of single-particle wavefunctions, even when the constituent particles are entirely distinct. Such 'entangled' states explicitly demonstrate the non-local character of quantum theory, having potential applications in high-precision spectroscopy, quantum communication, cryptography and computation. In general, the more particles that can be entangled, the more clearly nonclassical effects are exhibited--and the more useful the states are for quantum applications. Here we implement a recently proposed entanglement technique to generate entangled states of two and four trapped ions. Coupling between the ions is provided through their collective motional degrees of freedom, but actual motional excitation is minimized. Entanglement is achieved using a single laser pulse, and the method can in principle be applied to any number of ions.

Journal Article↗

Measurement of the 1s-2s energy interval in muonium

The 1s-2s interval has been measured in the muonium (&mgr;(+)e(-)) atom by Doppler-free two-photon pulsed laser spectroscopy. The frequency separation of the states was determined to be 2 455 528 941.0(9.8) MHz, in good agreement with quantum electrodynamics. The result may be interpreted as a measurement of the muon-electron charge ratio as -1-1.1(2.1)x10(-9). We expect significantly higher accuracy at future high flux muon sources and from cw laser technology.

Journal Article↗

Solar photo-oxidative disinfection of drinking water: preliminary field observations.

The feasibility of using solar photo-oxidation to inactivate faecal bacterial contaminants in drinking water has been evaluated under field conditions in India and South Africa. Freshly drawn samples from all six test water sources were low in dissolved oxygen, at 13-40% of the air saturation value. However, vigorous mixing followed by exposure to full-strength sunlight in transparent plastic containers (1-25 l capacity) caused a rapid decrease in the counts of faecal indicator bacteria, giving complete inactivation within 3-6 h, with no evidence of reactivation. These results demonstrate that solar photo-oxidation may provide a practical, low-cost approach to the improvement of drinking water quality in developing countries with consistently sunny climates.

Colony Count, Microbial↗

Novel human gene transfer vectors: evaluation of wild-type and recombinant animal adenoviruses in human-derived cells.

Major disadvantages of human adenovirus (hAd) vectors in gene therapy include preexisting or induced immune responses, and possible coreplication of recombinant hAd in the presence of wild-type hAds. These disadvantages may be overcome by using nonhuman, animal adenoviruses (aAds). We evaluated four different aAds for their potential use as viral vectors. The canine adenovirus type 2 (CAV2) and bovine adenovirus type 3 (BAV3) appeared to be suitable systems, as they infect human cells. CAV2, but not BAV3, caused cytotoxicity, and only limited (CAV2) or no (BAV3) production of infectious virus particles was observed after infection of human cell lines. CAV2 showed higher expression of endogenous genes than did BAV3 in the tested human cells. No interference between hAd and CAV2 or BAV3, such as recombination of DNA or cross-activation of virus replication, was observed in up to five passages in double-infected human cells. Transfection of cloned genomic CAV2 or BAV3 DNA into appropriate permissive cell lines rescued infectious virus. Furthermore, we produced a recombinant E1-deleted BAV3, and showed that it could infect and express a reporter gene in various human cell types. The goal was to construct and evaluate recombinant (E1-deleted) animal adenoviruses (aAds) as new vector systems for human gene therapy. The rationale for developing aAds for human use is the potential higher safety and efficiency, as compared with human adenoviruses (hAds). Coreplication and recombination with preexisting hAds should not be possible owing to lack of homology, and preexisting immunity in the general population should be limited. Of the four aAds we evaluated, BAV3 appeared to be the best candidate. It infects human cells without showing growth or cytotoxic effects, viral gene expression was barely detectable, and no trans-activation of either virus was detected in coinfections with hAd5. Rescue of virus in permissive cells, from plasmids containing the CAV2 or BAV3 genome, confirmed our approach. Furthermore, an E1-deleted recombinant BAV3 was constructed and shown to transduce and express the lacZ reporter gene in human cells.

Adenoviridae↗

Micrographic surgery ('slow Mohs') in cutaneous sarcomas.

BACKGROUND: Micrographic surgery (MS) results in very low local recurrence rates in all sorts of skin tumours that grow by extensive subclinical infiltration. Therefore, MS should prove useful in the treatment of cutaneous sarcomas. OBJECTIVE: To treat cutaneous sarcoma with MS in order to minimize local recurrence rates. METHODS: We treated 5 cases of dermatofibrosarcoma protuberans and 5 cases of cutaneous sarcomas of different origin (atypical fibroxanthoma, malignant fibrous histiocytoma, malignant peripheral nerve tumour) with micrographic surgery using paraffin-embedded sections. In primary cutaneous sarcomas, tumour extensions were readily detected in HE sections. In recurrent tumours, special stains were needed to distinguish tumour extensions from scar tissue. RESULTS: All patients were treated successfully and have remained free of local recurrences as of yet. Solitary pulmonary metastasis occurred in 1 patient with high-grade malignant peripheral nerve tumour. CONCLUSION: MS is an excellent procedure to minimize local recurrence in cutaneous sarcomas. Cutaneous sarcomas with low metastatic potential can be cured with MS.

Adult↗

Physiological and endocrine changes associated with polydnavirus/venom in the parasitoid-host system Chelonus inanitus-Spodoptera littoralis.

As shown earlier, parasitization by the egg-larval parasitoid C. inanitus causes in its host the precocious onset of metamorphosis in the 5th instar followed by developmental arrest in the prepupal stage. Polydnavirus/venom were shown to be responsible for the developmental arrest. We investigated how polydnavirus/venom affect growth of the host larvae and found that head capsule widths were smaller from the 4th to 6th stadium and weights were lower in the 6th stadium in polydnavirus/venom-containing larvae than in non-parasitized larvae. In an attempt to identify endocrine parameters that are modified by polydnavirus/venom and might be responsible for the developmental arrest in the prepupa, we compared juvenile hormones, juvenile hormone esterase and ecdysteroids between non-parasitized and polydnavirus/venom-containing larvae from the 4th instar until pupation or developmental arrest, respectively. Obvious differences became manifest only in the 6th instar at the pupal cell formation stage, i.e. 12 days after entry of polydnavirus/venom into the host egg. Then, prothoracic glands of polydnavirus/venom-containing larvae released less ecdysteroids and ecdysteroid titres were lower than in non-parasitized larvae; this was followed by a delayed, reduced and desynchronized increase in prepupal juvenile hormones and juvenile hormone esterase and a slightly modified metabolism of ecdysone. This indicates that polydnavirus/venom affects the endocrine system of the host only after pupal commitment and that inhibition of prothoracic gland activity is the first detectable effect.

Journal Article↗

TAL1 expression does not occur in the majority of T-ALL blasts.

The TAL1 gene is disrupted by translocation or deletion (tal(d)) in up to 30% of T-cell acute lymphoblastic leukaemia (T-ALL), leading to aberrant transcriptional activation, as a SIL-TAL1 fused transcript in tal(d). It has been suggested that TAL1 transcription occurs in approximately 50% of a T-ALLs without apparent rearrangement. SIL-TAL1 was positive in 15/60 (25%) of T-ALL, whereas wild-type TAL1 transcripts were detected in all 13 SIL-TAL1 and in 19/43 (44%) T-ALL without SIL-TAL1. To investigate the cellular origin of TAL1 we exploited the fact that GATA1 and TAL1 are co-ordinately expressed in non-lymphoid haemopoietic cells, whereas only the latter is found in T-ALL. GATA1 was detected in 10/23 (43%) TAL1-negative T-ALLs but in 17/19 (89%) 'unexplained' TAL1-positive cases, suggesting a common non-lymphoid cellular origin. Immunocytochemical analysis with a TAL1-specific monoclonal antibody showed nuclear expression in the blasts of 10/34 (29%) cases, including 8/10 SIL-TAL1+ and two RT-PCR TAL1+, SIL-TAL1- cases. In the remaining cases TAL1 expression was restricted to a minor population (< 5%) of larger, strongly TAL1-positive cells which comprised erythroid cells, CD34+ CD3- precursors and an unidentified TAL1+ CD45- population which morphologically resembled monocytes/macrophages. We therefore suggest that appropriate diagnostic evaluation of T-ALL should include molecular detection of SIL-TAL1 transcripts and in situ immunocytochemical detection of TAL1 protein expression by leukaemic blasts. This approach will enable accurate analysis of the prognostic significance of TAL1 deregulation in T-ALL.

Adolescent↗

Multiple developmental requirements of noisette, the Drosophila homolog of the U2 snRNP-associated polypeptide SP3a60.

We report the cloning of the noisette gene (noi), which encodes the Drosophila melanogaster ortholog of a U2 snRNP-associated splicing factor, SF3a60 (SAP61) in humans and PRP9p in Saccharomyces cerevisiae. Antibodies raised against human SF3a60 recognized NOI in flies, showing a nuclear localization in all the stages examined, including the embryo, the dividing cells of imaginal discs, and the larval polyploid nuclei. NOI is expressed in somatic and germinal cells of both male and female gonads. By mobilization of P transposons, we have generated a large number of noi mutations. Complete loss of function resulted in lethality at the end of embryogenesis, without obvious morphological defects. Hypomorphic alleles revealed multiple roles of noi for the survival and differentiation of male germ cells, the differentiation of female germ cells, and the development of several adult structures.

Alleles↗

Interleukin-7, a non-redundant potent cytokine whose over-expression massively perturbs B-lymphopoiesis.

Interleukin-7, originally described as a factor controlling the survival of B-cell progenitors, has been shown by gene knock-out technology to be a non-redundant cytokine. Of all single cytokine knock-out mice, those in which the IL-7 gene has been ablated show a profound defect in lymphocyte development. Likewise, mice in which signals emanating from the corresponding receptor, whether it be by ablation of the unique alpha or common gamma chain of the receptor, or by interference with downstream signalling elements generated by this receptor complex, also show profound defects in lymphocyte differentiation. Transgenic mice over-expressing the IL-7 gene also show profound changes in lymphocyte development which, in some instances can result in the development of lymphoid tumours. Here, we review some of these aspects of IL-7 biology with particular reference to an IL-7 over-expressing transgenic mouse line in which the IL-7 transgene is controlled by the mouse MHC class II promoter.

Animals↗

[Respective influence of occupational and personal factors on respiratory function in dairy farmers].

Occupational and individual factors influencing respiratory function were analysed in a sample of dairy farmers. The study protocol included a medical questionnaire, an occupational questionnaire, spirometry and allergological tests (skin prick tests for a panel of inhalant allergens, serum total IgE level and Phadiatop (CAP System). Two hundred and forty-five farmers were studied (140 men, 105 women with an average age of 45.9 (11.3) years, 35 were smokers, 27 ex-smokers and 183 non-smokers). A multiple linear regression model was used to analyse the correlations between respiratory function and the different independent variables. There was a statistically significant negative correlations between smoking (expressed in pack-years) and all the respiratory function parameters (p < 0.01). Respiratory function was significantly impaired in farmers working on traditional farms (p < 0.05 for VC and for FEV1), and the respiratory function values increased proportionally with the modernisation of the farms (notably using an artificial barn drying system for hay and a ventilation system for the cow byres). No significant relationship between respiratory function and quantitative indicators of exposure (size of farm, amount of livestock, quantity of hay handled during professional lifetime) or indicators of IgE-mediated allergy was observed. In conclusion, this study suggests that traditional work conditions in farms which have little mechanisation are, along with tobacco, the determining factors for the respiratory function impairment in dairy farmers.

Adult↗

Endoscopic detection of early esophageal cancer in a high-risk population: does Lugol staining improve videoendoscopy?

BACKGROUND: The aim of this study was to prospectively compare the diagnostic accuracy of videoendoscopy, with and without Lugol staining, for the detection of esophageal cancer in alcoholic or smoking patients older than 40 years. METHODS: Daily alcohol and tobacco consumption and overt and latent symptoms were noted. The 158 patients included were examined by videoendoscopy and with Lugol dye. RESULTS: The mean consumption of alcohol and tobacco was 86 +/- 49 gm/day for 26 +/- 11 years, and 30 +/- 18 pack-years, respectively. Twenty-five patients had no symptoms. Before Lugol staining, 12 patients had endoscopically identified cancerous lesions. After Lugol staining, 13 patients had 17 esophageal cancers, 3 of which were high-grade dysplasia. The prevalence of esophageal cancer was 8.2%: 95% CI [4,14]. Dye-free surfaces were significantly larger than the endoscopic patterns observed before Lugol staining (11.6 +/- 9.2 cm2 vs 1.4 +/- 1.7 cm2; p < 0.02). CONCLUSIONS: In an alcoholic smoking population, the prevalence of esophageal cancer detected by endoscopy is high and not related to symptoms described by patients. Lugol staining only moderately improves the diagnostic accuracy of videoendoscopy; its main advantage is the assessment of the mucosal extension of esophageal cancer.

Adult↗

Evidence for multiple, local functions of ciliary neurotrophic factor (CNTF) in retinal development: expression of CNTF and its receptors and in vitro effects on target cells.

There is increasing, although largely indirect, evidence that neurotrophic factors not only function as target-derived survival factors for projection neurons, but also act locally to regulate developmental processes. We studied the expression of ciliary neurotrophic factor (CNTF) and the CNTF-specific ligand-binding alpha-subunit of the CNTF receptor complex (CNTFR alpha) in the rat retina, a well-defined CNS model system, and CNTF effects on cultured retinal neurons. Both CNTF and CNTFR alpha (mRNA and protein) are expressed during phases of retinal neurogenesis and differentiation. Retina-specific Müller glia are immunocytochemically identified as the site of CNTF production and CNTFR alpha-expressing, distinct neuronal cell types as potential CNTF targets. Biological effects on corresponding neurons in culture further support the conclusion that locally supplied CNTF plays a regulatory role in the development of various retinal cell types including ganglion cells and interneurons.

Animals↗

Incidence, case fatality, risk factors of acute coronary heart disease and occupational categories in men aged 30-59 in France.

OBJECTIVES: To assess the incidence and case fatality rate (CFR) from acute coronary insufficiency in men among occupational categories and to analyse the relationship between these disparities and the distribution of cardiovascular risk factors in the French population. SETTING: Three registers of the WHO-MONICA project in France: the urban area of Lille and two French districts: Bas-Rhin and Haute-Garonne. METHODS: Two sets of data were used: 1) the incident cases collected by the three MONICA Collaborating Centres (MCC) of the French WHO-MONICA Project (Lille, Strasbourg and Toulouse), between 1985 and 1989; 2) a cross-sectional study on cardiovascular risk factor prevalence performed in 1985-1989 in the three areas corresponding to the MCC. SUBJECTS: The data concern 5133 new coronary events in men aged 30-59 and a sample of 1863 men aged 30-59. RESULTS: A strong relationship was observed between occupational categories and the incidence of acute myocardial infarction and coronary events as well as CFR. Both incidence and CFR were lower among senior executives. Incidence was higher among employees and workers. However, employees, as opposed to unskilled workers, did not have higher CFR. Using occupational category as a statistical unit, the incidence of first acute myocardial infarction and coronary events was associated with the prevalence of smokers in the population (r = 0.50, P = 0.06 and r = 0.61, P = 0.02). The CFR was associated with systolic blood pressure (r = 0.82, P = 0.002), and the prevalence of smokers (r = 0.65, P = 0.02). None of the measures of incidence or case fatality among categories was related to cholesterol, HDL-cholesterol or body mass index. CONCLUSIONS: Strong differences were observed between occupational categories and the incidence of acute myocardial infarction, coronary events and CFR. These differences were found to be closely related to the social distribution of two major cardiovascular risk factors: tobacco smoking and blood pressure.

Adult↗

Interaction of tryptamine and ergoline compounds with threonine 196 in the ligand binding site of the 5-hydroxytryptamine6 receptor.

We examined the ligand-binding site of the 5-hydroxytryptamine6 (5-HT6) receptor using site-directed mutagenesis. Interactions with residues in two characteristic positions of trans-membrane region V are important for ligand binding in several bioamine receptors. In the 5-HT6 receptor, one of these residues is a threonine (Thr196), whereas in most other mammalian 5-HT receptors, the corresponding residue is alanine. After transient expression in human embryonic kidney 293 cells, we determined the effects of the mutation T196A on [3H]d-lysergic acid diethylamide (LSD) binding and adenylyl cyclase stimulation. This mutation produced a receptor with a 10-fold reduced affinity for [3H]LSD and a 6-fold reduced affinity for 5-HT. The potency of both LSD and 5-HT for stimulation of adenylyl cyclase was also reduced by 18- and 7-fold, respectively. The affinity of other N1-unsubstituted ergolines (e.g., ergotamine, lisuride) was reduced 10-30 fold, whereas the affinity of N1-methylated ergolines (e.g., metergoline, methysergide, mesulergine) and other ligands, such as methiothepine, clozapine, ritanserin, amitriptyline, and mainserin, changed very little or increased. This indicates that in wild-type 5-HT6 receptor, Thr196 interacts with the N1 of N1-unsubstituted ergolines and tryptamines, probably forming a hydrogen bond. Based on molecular modeling, a serine residue in transmembrane region IV of the 5-HT2A receptor has previously been proposed to interact with the N1-position of 5-HT. When the corresponding residue of the 5-HT6 receptor (Ala154) was converted to serine, no change in the affinity of twelve 5-HT6 receptor ligands or in the potency of 5-HT and LSD could be detected, suggesting that this position does not contribute to the ligand binding site of the 5-HT6 receptor.

Amino Acid Sequence↗

Both IFN-gamma and IL-4 induce MHC class II expression at the surface of mouse pro-B cells.

Pro-B cells are early B-cell progenitors that retain macrophage potential. We have studied MHC class II molecules and invariant chain inducibility on four class II negative mouse pro-B-cell clones. We analyzed the effects of IL-4 and IFN-gamma, which represent the major inducers of class II in the B-lymphoid and monocytic/macrophage lineages, respectively. After 48 h of treatment with either cytokine, three pro-B-cell clones (C2.13, A1.5, and F2.2) expressed intracellular invariant chain and cell-surface class II molecules. One clone (D2.1) remained negative. As already reported, more differentiated 70Z/3 pre-B cells were inducible by IL-4 only. These data suggest that the induction of class II and invariant-chain genes are subject to regulation throughout B-cell differentiation.

Animals↗

Phenotypic and functional analysis of B lymphopoiesis in interleukin-7-transgenic mice: expansion of pro/pre-B cell number and persistence of B lymphocyte development in lymph nodes and spleen.

Transgenic mice in which mouse interleukin (IL)-7 cDNA is expressed under the control of the mouse major histocompatibility complex (MHC) class II (E alpha) promoter develop a lymphoproliferative disease characterized by the early polyclonal expansion of T cells followed in many cases by the development of lymphomas of immature B cells. Here, we have analyzed B cell development in these transgenic mice. Phenotypic analysis using monoclonal antibodies to B220, IgM, IgD, c-kit, IL-7 receptor, MHC class II, AA4.1, CD19, CD23, CD25, CD40 and CD43 shows that B lymphopoiesis in the bone marrow is dramatically altered and the number of pro/pre-B and immature B cells is significantly increased. Interestingly, pro/pre-B and immature B cells persist in the spleens of adult transgenic mice and are also present in lymph nodes and blood. Cell cycle analysis of lymph node cells shows that subpopulations of developing B cells retain the cell cycle profiles of their bone marrow counterparts. Limiting dilution analysis shows that the number of clonable pre-B cells is significantly increased and that at limiting dilution, growth of transgenic pre-B cells is still dependent on exogenous IL-7. Using semiquantitative polymerase chain reaction (PCR) and in situ hybridization, the level of IL-7 transcripts in the spleen was found to decrease between 2 and 4 weeks in control mice with levels in transgenics mice being approximately 50 times greater. These transgenic mice represent an interesting model with which to study the effects of IL-7 overexpression in the bone marrow and raise interesting questions regarding the regulation of B lymphopoiesis in normal mice.

Animals↗