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Biomedical subjects

L Nicol

Publications and source records attributed to L Nicol.

17 recordsLinked to original sources
PubMed1995

Hemodynamic importance of preserving the normal sequence of ventricular activation in permanent cardiac pacing.

Pacing the right ventricle in the apex profoundly modifies the sequence of activation and thus the sequence of contraction and relaxation of the left ventricle. To evaluate the relative importance of preserving normal ventricular activation sequence and optimal atrioventricular (AV) synchrony in permanent pacing, we compared the effects of three pacing modes: AAI, preserving both normal AV synchrony and normal activation sequence; DDD, with complete ventricular capture that preserves only AV synchrony; and VVI, disrupting both, at rest and during exercise. Hemodynamic and radionuclide studies were performed in 11 patients who had normal intrinsic conduction and who were implanted on a long-term basis with a DDDR pacemaker for isolated sinus node dysfunction. AAI versus DDD and VVI significantly increased cardiac output at rest (6.6 +/- 1.3 L/min vs 6 +/- 0.9 L/min vs 5 +/- 1 L/min; p < 0.01) and during exercise (13.5 +/- 2 L/min vs 12.1 +/- 2.2 L/min vs 14.4 +/- 2.1 L/min; p < 0.01). Pulmonary capillary wedge pressure was lowest with AAI (15.4 +/- 4.5 mm Hg), with an average reduction of 17% compared with DDD (19.6 +/- 5 mm Hg; p < 0.01) and of 30% compared with VVI (25.8 +/- 7 mm Hg; p < 0.01) during exercise. Identical benefits were observed for all other hemodynamic parameters: right atrial pressure, pulmonary artery pressure, left ventricular (LV) stroke work index, and systemic vascular resistances. LV ejection fraction was significantly higher in AAI than in DDD at rest (61% vs 58%, respectively; p < 0.05) and during exercise (65% vs 60%, respectively; p < 0.05). This improvement in LV systolic function resulted principally from the increase in septal ejection fraction. LV filling also was improved in AAI as demonstrated by a significant increase in peak filling rate at rest and during exercise. These data show the importance of preserving, whenever possible, not only normal AV synchrony but also normal ventricular activation sequence in permanent cardiac pacing.

Adult↗
PubMed1995

CENP-B binds a novel centromeric sequence in the Asian mouse Mus caroli.

Minor satellite DNA, found at Mus musculus centromeres, is not present in the genome of the Asian mouse Mus caroli. This repetitive sequence family is speculated to have a role in centromere function by providing an array of binding sites for the centromere-associated protein CENP-B. The apparent absence of CENP-B binding sites in the M. caroli genome poses a major challenge to this hypothesis. Here we describe two abundant satellite DNA sequences present at M. caroli centromeres. These satellites are organized as tandem repeat arrays, over 1 Mb in size, of either 60- or 79-bp monomers. All autosomes carry both satellites and small amounts of a sequence related to the M. musculus major satellite. The Y chromosome contains small amounts of both major satellite and the 60-bp satellite, whereas the X chromosome carries only major satellite sequences. M. caroli chromosomes segregate in M. caroli x M. musculus interspecific hybrid cell lines, indicating that the two sets of chromosomes can interact with the same mitotic spindle. Using a polyclonal CENP-B antiserum, we demonstrate that M. caroli centromeres can bind murine CENP-B in such an interspecific cell line, despite the absence of canonical 17-bp CENP-B binding sites in the M. caroli genome. Sequence analysis of the 79-bp M. caroli satellite reveals a 17-bp motif that contains all nine bases previously shown to be necessary for in vitro binding of CENP-B. This M. caroli motif binds CENP-B from HeLa cell nuclear extract in vitro, as indicated by gel mobility shift analysis. We therefore suggest that this motif also causes CENP-B to associate with M. caroli centromeres in vivo. Despite the sequence differences, M. caroli presents a third, novel mammalian centromeric sequence producing an array of binding sites for CENP-B.

Animals↗
PubMed1994

Human autoimmune sera recognize a conserved 26 kD protein associated with mammalian heterochromatin that is homologous to heterochromatin protein 1 of Drosophila.

Immunofluorescence indicated that autoimmune sera from certain scleroderma/CREST patients, in addition to binding to the primary constrictions or centromeres, also labelled pericentromeric heterochromatin in mouse and human metaphase chromosomes. Immunoblotting has revealed that two conserved nuclear antigens are recognized by this CREST subgroup, one of mol. wt 26 kD (p26), and the other of mol. wt 23 kD (p23). In situ immunolabelling with affinity purified antibodies demonstrated that p26, but not p23, is concentrated in pericentromeric heterochromatin. Further studies have shown that both p26 and p23 are immunologically related to the Drosophila heterochromatin-associated protein HP1, and to other chromodomain proteins.

Animals↗
PubMed1994

Analysis of centromere structure in the fly Megaselia scalaris (Phoridae, Diptera) using CREST sera, anti-histone antibodies, and a repetitive DNA probe.

We have used CREST anti-centromere sera, rabbit anti-histone antibodies, and repetitive DNA analysis to study centromere structure in the fly Megaselia scalaris (Phoridae). In a panel of eight CREST sera, four were positive in immunofluorescence experiments for prekinetochores, ie centromeres in interphase nuclei. The access of the antibodies to CREST antigens may be compromised in the condensed state, since centromeres of prometaphase and metaphase chromosomes remained unstained. When Western blots of embryonic nuclei were probed with these four CREST sera, three of them showed a 17 kDa band. Human CENP-A, likewise recognized by the CREST sera, is a 17 kDa protein. The remaining sera were negative for centromeres although some detected centrosomes and non-histone chromosomal proteins not confined to the centromeres. The use of antibodies generated against histone H4 acetylated at four different sites of the N-terminal domain revealed that heterochromatic regions of M scalaris mitotic chromosomes, ie pericentric and NOR-associated segments, are hyperacetylated. This is at variance with a variety of other systems, where transcriptionally active chromatin is hyperacetylated. Finally, a repetitive 165 base pair fragment was isolated from genomic DNA of the fly and sequenced. An oligonucleotide from this sequence mapped to the centromere region of interphase nuclei and the pericentric regions of condensed chromosomes.

Animals↗
PubMed1993

Novel structural organisation of a Mus musculus DBA/2 chromosome shows a fixed position for the centromere.

Chromosome 1 of the inbred mouse strain DBA/2 shows an unusual polymorphism associated with its centromeric satellite DNA sequences. The minor satellite array has undergone amplification and is present as two blocks separated by major satellite sequences. Both minor satellite blocks appear to carry the sequence motif necessary for CENP-B protein binding. Despite this apparent similarity the functional centromere, as defined by the location of CREST antigens, appears to form only within the more terminal block. The two blocks also vary in that sister chromatid association only occurs with this more terminal block.

Animals↗
PubMed1990

[Immunoscintigraphy of malignant melanoma].

This work is part of a multicentric European evaluation of the monoclonal antibody 225.28s targeted against malignant melanoma and its metastases. Twenty-eight patients (12 males, 16 females, mean age: 53 yrs), who had initially been treated by resection of the primary tumour, were included in the study. Twenty-three of the 26 metastases more than 1 cm in diameter were visualized by immunoscintigraphy. The sensitivity of the procedure (88%) is limited however by the small size of the lesions and their depth, as well as by background noise caused by circulating antibodies. Immunoscintigraphy enables non-invasive investigation of the whole body and can detect lesions that other conventional complementary explorations fail to identify.

Antibodies, Monoclonal↗
PubMed1986

Non-kinetochore directed autoantibodies in scleroderma/CREST. Identification of an activity recognizing a metaphase chromosome core non-histone protein.

Three scleroderma/CREST sera possessing anti-kinetochore autoantibody were tested by indirect immunofluorescence for reaction with isolated Chinese hamster metaphase chromosomes and histone-dissociated chromosome "scaffolds". All three sera revealed kinetochore staining on both whole chromosomes and histone-dissociated chromosomes, and confirmed previous reports that the kinetochore is part of the chromosome scaffold. Unexpectedly, one serum also recognized a non-centromere-located chromosomal antigen which is retained at the axial non-histone protein core following histone dissociation. The antigen is exclusively nuclear in origin, does not appear to be DNA or residual histone, and seems to correspond to a major component of the chromosome core. The existence of this antigen has important implications in terms of chromosome structure. Another CREST serum was shown to possess autoantibody against a cytoplasmic structural component, in addition to anti-kinetochore activity. The presence of anti-kinetochore and other autoantibody activities in CREST patient sera is discussed in relation to disease processes.

Animals↗
PubMed1986

[Evaluation of aortocoronary bypass using exercise myocardial thallium 201 scintigraphy].

The surveillance of aortocoronary bypass grafts is a difficult problem. Clinical examination and exercise testing are unable to give a complete evaluation of the operative results and cardiac catheterisation with radiological opacification of the grafts are not without risk and cannot be repeated periodically. Therefore, radioisotopic methods have been proposed as a means of assessing aortocoronary bypass grafts. The aim of this study was to evaluate postoperative myocardial perfusion by Thallium 201 scintigraphy. The authors compared pre and postoperative scintigraphies in 37 patients undergoing aortocoronary bypass surgery (36 men and 1 woman, average age: 53.9 years). Preoperative coronary angiography showed 9 cases of single vessel disease, 11 cases of double vessel diseases and 17 cases of triple vessel disease. Seventy one bypass grafts were performed (average 1.92 grafts/patient): 37 on the LAD, 15 on the circumflex, 10 on the diagonal and 9 on the right coronary. All patients were submitted to the same protocol before surgery and during the third postoperative month; Clinical examination, ECG, exercise stress testing and Thallium 201 myocardial scintigraphy. The results confirm the improvement in myocardial perfusion after coronary bypass surgery. The percentage of pathological scintigraphic segments fell from 42 per cent before surgery to 27 per cent after surgery (p less than 0.01). The total Thallium perfusion index improved significantly after surgery from 9.3 +/- 2 to 7.7 +/- 1.9 (p less than 0.01). Thallium 201 scintigraphy was superior to clinical examination and exercise testing in the assessment of graft patency, identifying 2 postoperative infarctions inapparent on clinical examination, excluding postoperative non-anginal chest pain and evaluating myocardial perfusion in patients who had sub maximal postoperative exercise stress tests. The relatively non traumatic character of Thallium 201 scintigraphy makes it the best non-invasive method of assessing aortocoronary bypass graft patency.

Adult↗
PubMed1981

Study of respiratory effect of short- and long-term cotton gin exposure.

No excess of obstructive airway disease was found in a group of 265 cotton gin workers when compared with other San Joaquin Valley agricultural workers. After an average of eight weeks' employment in San Joaquin Valley cotton gins, 125 workers showed no appreciable deterioration of pulmonary function compared with pre-employment measurements. In studies of pulmonary function during a workshift, cotton gin workers showed slightly greater mean decrements than control agricultural workers. These differences did not reach a level of statistical significance and were lower than those usually found in byssinosis. The unusual temporal pattern of employment in cotton gins in California precludes a simple approach to diagnosis by symptoms. No correlation was found in this study between symptoms of byssinosis and objective decrements in FEV1. The questionnaire as proposed by the Cotton Dust Standard was found to be of no value in detecting reactors in this study of gin workers.

Adolescent↗