Localization, dynamical correlations, and the effect of colored noise on coherence.
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Biomedical subjects
Publications and source records attributed to D Cohen.
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An approach to physical mapping is analyzed here. This procedure consists of fingerprinting random clones with single-copy landmarks extracted randomly from a region of interest. Results are presented in terms of number of contigs (sets of overlapping clones), number of isolated clones, average length of a contig, and coverage of the genome by contigs larger than a given size. (i) The expected results of an ideal project are presented. (ii) Certain problems that could influence progress of the map (variability in clone insert length, double inserts, etc.) are considered. (iii) An optimal project, which consists of a 7-fold representative library fingerprinted with an average of five sequence-tagged sites per clone, is analyzed. (iv) We present strategical considerations for the proposed approach, and a strategy that minimizes the number of laboratory tests without significant information loss is proposed: clones are arranged on a matrix and pooled according to rows and columns. A fingerprint is determined for each pool, and analysis allows retrieval of the positive clones. This method reduces the number of laboratory tests done by a factor of 160.
The effect of control of houseflies on the incidence of diarrhoea and shigellosis was evaluated in a prospective crossover intervention study at two military field bases several kilometers apart. In early summer, 1988, intensive fly control measures (mainly bait and trap strategy) were introduced on one base, while the other served as a control. After 11 weeks, as new cohorts arrived, the intervention was abruptly discontinued in the first base and instituted in the second for the next 11 weeks. The study was repeated the next summer. Overall, fly counts were 64% lower on the bases exposed to fly control measures (p = 0.024). Concomitantly, clinic visits dropped by 42% (p = 0.146) for diarrhoeal diseases and by 85% for shigellosis (p = 0.015), as did rates of seroconversion, by 76% (p = 0.024) for antibodies to Shigella and by 57% (p = 0.006) for antibodies to enterotoxigenic Escherichia coli. The findings indicate that houseflies, acting as mechanical vectors, transmit Shigella (and possibly enterotoxigenic E coli) diarrhoeal infections.
Yeast artificial chromosomes (YACs) were obtained from a 550-kilobase region that contains three probes previously mapped as very close to the locus of the fragile X syndrome. These YACs spanned the fragile site in Xq27.3 as shown by fluorescent in situ hybridization. An internal 200-kilobase segment contained four chromosomal breakpoints generated by induction of fragile X expression. A single CpG island was identified in the cloned region between markers DXS463 and DXS465 that appears methylated in mentally retarded fragile X males, but not in nonexpressing male carriers of the mutation nor in normal males. This CpG island may indicate the presence of a gene involved in the clinical phenotype of the syndrome.
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A rapid and safe method of Yeast Artificial Chromosome (YAC) physical mapping by cosmid 'fingerprinting' is presented. YACs are subcloned into cosmids which are prepared without previous separation of cloned DNA from host DNA. Groups of overlapping clones are detected according to their restriction fragments size and intensity after hybridization with total human DNA. To test this approach, a cosmid library was constructed from total DNA of a yeast strain containing a 420 kb YAC. A single contig of 84 clones was obtained with a minimal detectable overlap of 60% i.e. a 9.2 fold representative library. Large scale physical mapping of YACs would take full advantage of the DNA preparation procedure employed in this work and allows to take into account restriction fragment intensities.
The overproduction of P-glycoprotein, an integral membrane protein thought to function as a drug efflux pump, is the hallmark of the multidrug resistance phenotype. In murine multidrug resistant J774.2 cell lines, distinct mdr genes, mdr1a and mdr1b, encode unique P-glycoprotein isoforms. To examine the transcriptional regulation of the mdr1b gene, its promoter was isolated and characterized. The transcription initiation site was mapped by primer extension, and the 5'-flanking region was sequenced. Several potential regulatory elements were identified in this region. A transient expression vector was constructed by fusion of 540 base pairs of 5'-flanking sequence and part of the first untranslated exon to the chloramphenicol acetyltransferase (CAT) gene. When transfected into monkey kidney COS-1, rat pituitary GH3 or T47D human breast cells, the mdr1b 5'-flanking sequences were capable of driving CAT expression. Transient transfection studies using deletion subclones of the mdr1b-CAT construct were done to locate potential cis-acting sequences. The studies indicate the presence of cis-acting elements in the 5'-flanking region of the mdr1b gene. The implications of these findings for expression and regulation of the mdr1b gene are discussed.
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We describe a case of inflammatory pseudotumor of the lower abdomen in a young child. The urinary bladder and abdominal wall were involved, and the pseudotumor simulated a malignant sarcomatous tumor. Surgical excision was undertaken, and the outcome was favorable. This rare tumor simulates a true neoplasm both clinically and morphologically and presents a diagnostic and therapeutic dilemma. Our case and a review of the literature indicate that an effort should be made to perform a radical excision. This is considered the treatment of choice except if it requires a mutilating procedure.
The accuracy with which electrical sources in the brain can be localized by using electroencephalograms measured on the scalp is not well known. In this study, tests of localization accuracy were performed by using implanted dipolar sources in the human brain. These dipoles are created by passing a weak (subthreshold) current through intracerebral electrodes implanted in the brains of epileptic patients for seizure monitoring. The locations of these dipoles are accurately known from roentgenographs. First, 16 electroencephalograms produced by these dipoles were recorded, then inverse solutions were calculated for the apparent sources of these electroencephalograms. Finally, the locations of the apparent sources were compared with the known locations of the implanted dipoles to determine localization error. The average localization error for a total of 28 dipoles in 3 subjects was 1.1 cm. These results indicate that good localization accuracy for focal sources in the brain can be provided by scalp electroencephalograms.
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Temporal lobe epilepsy is diagnosed by clinical symptoms and signs and by localization of an epileptogenic focus. A brain SPECT study of two patients with temporal lobe epilepsy, using 99mTc-HMPAO, was used to demonstrate a perfusion abnormality in the temporal lobe, while brain CT and MRI were non-contributory. The electroencephalogram, though abnormal, did not localize the diseased area. The potential role of the SPECT study in diagnosis and localization of temporal lobe epilepsy is discussed.
We first review the theoretical and computer modelling studies concerning localization accuracy of EEG and MEG, both separately and together; the source is here a dipole. The results show that, of the three causes of localization errors, noise and head modelling errors have about the same effect on EEG and MEG localization accuracies, while the results for measurement placement errors are inconclusive. Thus, these results to date show no significant superiority of MEG over EEG localization accuracy. Secondly, we review the experimental findings, where there are again localization accuracy studies of EEG and MEG both separately and together. The most significant EEG-only study was due to dipoles implanted in the heads of patients, and produced an average localization error of 20 mm. Various MEG-only studies gave an average error of 2-3 mm in saline spheres and 4-8 mm in saline-filled skulls. In the one study where EEG and MEG localization were directly compared in the same actual head, again using dipoles implanted in patients, the average EEG and MEG errors of localization were 10 and 8 mm respectively. The MEG error was later confirmed by a similar (but MEG-only) experiment in another study, using a more elaborate MEG system. In summary, both theory and experiment suggests that the MEG offers no significant advantage over the EEG in the task of localizing a dipole source. The main use of the MEG, therefore, should be based on the proven feature that the MEG signal from a radial source is highly suppressed, allowing it to complement the EEG in selecting between competing source configurations.(ABSTRACT TRUNCATED AT 250 WORDS)
Tricuspid valve endocarditis traditionally has been treated with either valve excision or valve replacement. To avoid implantation of foreign material in an infected field, we have applied the principles of mitral valve repair to 4 patients with tricuspid valve endocarditis. On preoperative echocardiography, all patients had 3 to 4+ tricuspid regurgitation, evidence of progressive right ventricular enlargement, and mobile vegetations. In each case, up to three quarters of the anterior leaflet was excised en bloc with infected chordae and papillary muscle heads. Surgical procedures included standard quadrangular resection, conversion to a bicuspid valve, and pericardial patch replacement of the anterior leaflet with mobilization of basal chordae to replace resected marginal chordae. On postoperative echocardiography, tricuspid regurgitation and right ventricular dimensions were reduced in 2 of 4 patients in spite of loss of leaflet tissue. All excised valve tissue demonstrated bacteria on Gram stain or culture. Nonetheless, all repaired valves were successfully sterilized without recurrent infections. Tricuspid valve repair can allow eradication of infection with potential for improving valve competency in complicated tricuspid valve endocarditis.
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In a European collaboration, a joint project to conduct an experimental and clinical investigation of recently developed sensors from three centres (Amsterdam, Cambridge and Edinburgh) has been carried out. The Amsterdam sensor was based on an inductive principle whereas the Cambridge and Edinburgh transducers used a piezo-electric material (PVDF) as transducing element. Nine patients with varying gestational age (29-38 weeks) were measured in a clinical investigation. Recordings of fetal heart sounds (FHS) and fetal breathing movements (FBM) were made using three sensors; one from each centre. These recordings were digitized directly into a computer using a purpose-built data acquisition system. For each patient 3 min of FBM data, and 1 min of FHS data were recorded by each sensor. The FBM recordings were carried out simultaneously with ultrasound, so as to enable a correlation to be made between both recordings. The FHS recordings were carried out simultaneously with the maternal heart pulse, to discount any maternal heart influences on the resulting signals. Of the nine patients analysed, FHS were recorded in seven patients. On the other hand, it appeared difficult to identify fetal breathing movements in the FBM recordings due to the dominance of the maternal breathing component. The analysis of the FBM signals and its correlation with ultrasound could not be carried out due to the relatively poor quality of the signals detected by the sensors, given the present techniques of analysis. The evaluation of the FHS recordings showed that although there is relatively little difference between the sensors, the inductive sensor performed best.