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Biomedical subjects

M O'Connor

Publications and source records attributed to M O'Connor.

At least 145 records · Page 8Linked to original sources
PubMed1995

Implantation of a subcutaneous lead array in combination with a transvenous defibrillation electrode via a single infraclavicular incision.

Occasional patients have excessive defibrillation energy requirements despite appropriate transvenous defibrillation lead position and modification of defibrillation waveform and configuration. Preliminary data suggest that use of subcutaneous defibrillation electrode arrays with nonthoracotomy systems is associated with a substantial reduction in defibrillation threshold. The current operative approach to subcutaneous lead array implantation involves the use of a separate left chest incision. We present two cases in which implantation of a subcutaneous lead array in combination with a transvenous defibrillation electrode was performed via a single infraclavicular incision and associated with a reduction in defibrillation threshold. Such an approach simplifies implantation and avoids the potential morbidity of the additional incision required of a left lateral chest approach.

Aged↗
PubMed1995

Variation of human papillomavirus type 6 (HPV-6) and HPV-11 genomes sampled throughout the world.

We examined the genomic diversity of human papillomavirus type 6 (HPV-6) and HPV-11 isolates from different parts of the world by comparing the nucleotide sequences of part of the long control region of three reference clones and 62 HPV-6 and 40 HPV-11 isolates from Africa, Europe, Asia, and North and South America. The genomic sequence of the HPV-6b reference type had to be amended by inclusion of a 94-bp segment, which is also present with minor differences in HPV-6a. Aside from two small inserts typical of all variants related to HPV-6a and three inserts found in HPV-11 variants, no major alterations to the size of the long control regions of these viruses were observed. This corrects the previous impression that these two HPV types are highly polymorphic. Altogether, 19 HPV-6 and 10 HPV-11 variant genomes could be distinguished, and most of the differences were due to point substitutions. The variants of either type were continuously connected in phylogenetic trees rather than clustered separately into subtype groups. Thirteen mutations, namely, the two HPV-6a inserts and 11 substitutions in HPV-6 or HPV-11 variants, reduced the dissimilarity between the types, but they bridged only a small fraction of the genetic distance between the two types. Genomes more obviously intermediate between HPV-6 and HPV-11 were not found and probably do not exist any more. A single HPV-11 variant was found in Africa, but otherwise, no significant correlations of HPV-6 or HPV-11 variants with geography or ethnicity of the patient cohort were found. Functional analysis of diverse enhancer variants showed activities that differed two-to threefold, and it must be considered that transcriptional differences may alter the biology or pathology of these viruses. Similar variants were found in lesions from anatomically different sites and in both benign and malignant lesions.

Base Sequence↗
PubMed1995

Functional reconstruction of trans regulation of the Ultrabithorax promoter by the products of two antagonistic genes, trithorax and Polycomb.

Maintenance of the "on-off" state of Drosophila homeotic genes in Antennapedia and bithorax complexes requires activities of the trithorax and Polycomb groups of genes. To identify cis-acting sequences for functional reconstruction of regulation by both trithorax and Polycomb, we examined the expression patterns of several Ubx-lacZ transgenes that carry upstream fragments corresponding to a region of approximately 50 kb. A 14.5-kb fragment from the postbithorax/bithoraxoid region of Ultrabithorax exhibited proper regulation by both trithorax and Polycomb in the embryonic central nervous system. Using a Drosophila haploid cell line for transient expression, we found that trithorax or Polycomb can function independently through this upstream fragment to activate or repress the Ultrabithorax promoter, respectively. Studies of deletion mutants of trithorax and Polycomb demonstrated that trithorax-dependent activation requires the central zinc-binding domain, while Polycomb-dependent repression requires the intact chromodomain. In addition, trithorax-dependent activity can be abrogated by increasing the amount of Polycomb, suggesting a competitive interaction between the products of trithorax and Polycomb. Deletion analysis of this fragment demonstrated that a 440-bp fragment contains response elements for both trithorax and Polycomb. Furthermore, we showed that the integrity of the proximal promoter region is essential for trithorax-dependent activation, implicating a long-range interaction for promoter activation.

Animals↗
PubMed1995

Surgical management of third nerve palsy.

AIMS: A surgical technique has been developed in order to obtain ocular alignment in the primary position in patients with third nerve palsy. METHODS: A method for surgically correcting the vertical deviation and the pseudoptosis is described in three patients with longstanding third nerve palsy. By decreasing the ability of the non-involved eye to elevate, a fixation duress was created which eliminated the secondary deviation that characteristically occurs in such patients when the involved eye fixates. As a result of this technique, both eyes in all patients on attempted fixation were under similar duress, therefore requiring equal amounts of stimulation to move into the primary position. When the fixation duress was sufficient, elimination of the hypotropia and ptosis was achieved. Additionally, in order to correct the exotropia, generous recession and resection procedures in the involved eye and recession of the lateral rectus in the noninvolved eye were performed. RESULTS: Between 8 and 10 prism dioptres of esotropia were achieved and maintained in two patients. One patient had 20 prism dioptres of exotropia. Two patients had no residual ptosis and one required an additional anterior levator resection to achieve a satisfactory result. CONCLUSION: Patients with a third nerve palsy and a pseudoptosis may be candidates for this approach.

Adolescent↗
PubMed1995

Effect of insulin-like growth factor I in murine muscular dystrophy.

In muscular dystrophy there is an imbalance between muscle protein synthesis and protein degradation, resulting in net muscle catabolism and progressive muscle weakness and wasting. Both insulin and insulin-like growth factor I (IGF-I) are known to have an anabolic effect on skeletal muscle, which is believed to be enhanced in the presence of elevated concentrations of amino acids. We examined the effects of 4-week administration of recombinant human IGF-I (rhIGF-I), both alone and supplemented with a high protein diet (HPD), on muscle metabolism, morphology, and function in the 129 ReJ dystrophic mouse. rhIGF-I significantly reduced muscle protein degradation (P < 0.001), increased muscle protein content (P < 0.05), decreased fiber area variability (P < 0.01), and increased hind limb utilization (P < 0.01). Supplementation of rhIGF-I therapy with a HPD resulted in a significant increase in muscle protein synthesis (P < 0.05) in addition to a further increase in the above parameters. We conclude that rhIGF-I causes an improvement in muscle metabolism, morphology, and function in dystrophic mice, and this effect is further enhanced by the presence of a HPD.

Animals↗
PubMed1995

A mutation at the universally conserved position 529 in Escherichia coli 16S rRNA creates a functional but highly error prone ribosome.

A base substitution of G to U was constructed at position 529 in Escherichia coli 16S rRNA. The U529 mutant ribosomes were functional and present on polysomes but were highly error prone and caused a progressive loss of cell viability. They displayed elevated levels of readthrough of stop codons and frameshifting, and an increase in thermal sensitivity of beta-galactosidase, suggestive of missense errors. These results demonstrate that the university conserved G529 is involved in tRNA selection at the A site during protein synthesis.

Base Sequence↗
PubMed1994

Biopsy-derived adult human brain tau is phosphorylated at many of the same sites as Alzheimer's disease paired helical filament tau.

Tau from Alzheimer's disease (AD) paired helical filaments (PHF-tau) is phosphorylated at sites not found in autopsy-derived adult tau from normal human brains, and this suggested that PHF-tau is abnormally phosphorylated. To explore this hypothesis, we examined human adult tau from brain biopsies and demonstrated that biopsy-derived tau is phosphorylated at most sites thought to be abnormally phosphorylated in PHF-tau. These sites also were phosphorylated in autopsy-derived human fetal tau and rapidly processed rat tau. The hypophosphorylation of autopsy-derived adult human tau is due to rapid dephosphorylation postmortem, and protein phosphatases 2A (PP2A) and 2B (PP2B) in human brain biopsies dephosphorylate tau in a site-specific manner. The down-regulation of phosphatases (i.e., PP2A and PP2B) in the AD brain could lead to the generation of maximally phosphorylated PHF-tau that does not bind microtubules and aggregates as PHFs in neurofibrillary tangles and dystrophic neurites.

Alzheimer Disease↗
PubMed1994

Measles vaccine: a 27-year follow-up.

In 1964, the Medical Research Council undertook a trial of measles vaccine in over 36,000 United Kingdom children; 9577 of whom received live vaccine, 10,625 received inactivated followed by live vaccines, and 16,328 acted as unvaccinated controls. Participants in this study have been followed to determine the long term protection from measles vaccine and follow-up data were available on 4194, 4638 and 274 respectively. During the 5-year period 1986-90, the protective efficacy of live measles vaccine has remained high at 87%, but the 95% confidence interval was wide (-43 to 99%) due to the small numbers of cases. Between 1976 and 1990, however, the overall efficacy of the live vaccine was 92% (95% confidence interval 86 to 95%) and there was no evidence of a decline in efficacy (P = 0.13) over the 15-year period. This study suggests that the protection from live measles vaccine persists for up to 27 years after vaccination, and that no change in the current United Kingdom measles immunization policy should be made on the grounds of waning immunity.

Child, Preschool↗
PubMed1994

Prevalence of HIV and associated risk behaviour in attendees at a Dublin needle exchange.

The aim of this study was to measure the prevalence of HIV infection and assess the level of equipment-sharing and unsafe sexual activity among attendees at a Dublin needle exchange. Using an anonymous unlinked approach, attendees were asked to complete a brief questionnaire and provide a sample of saliva for HIV testing. Of the 144 attendees eligible for inclusion during the study period, 106 agreed to participate and complete a questionnaire, a response rate of 74%. Of the 81 respondents who submitted a usable saliva sample, 14.8% were HIV positive. Half of the respondents claimed that they had not shared equipment during the preceding 28 days, but a third had shared with multiple partners. Half of the respondents claimed that they had multiple sexual partners during the preceding year, but only a quarter said that they always used condoms. The prevalence of HIV infection is similar to that found in routine linked testing of drug users in Ireland. The high level of unsafe injecting and sexual activity makes clear the need for more effective health promotion among drug users in Dublin.

Acquired Immunodeficiency Syndrome↗
PubMed1994

The Drosophila dorsal morphogen represses the tolloid gene by interacting with a silencer element.

The dorsal protein (DL) regulates the transcriptional activity of several genes that determine cell fate along the dorsoventral axis of the Drosophila melanogaster embryo. DL is present at high levels in ventral nuclei, where it activates some genes (twi and sna) and represses others (zen, dpp, and tld). DL shows homology to the Rel family of proteins and interacts with specific DNA sequences in the regulatory regions of its target genes. The distal portion of the zen gene acts as a silencer that can mediate the repression of a heterologous promoter in ventral regions of the embryo. It contains four DL binding sites which alone are sufficient for activation but not repression. Here we analyze the interaction of DL with another one of its repressed targets, the tolloid (tld) gene. Approximately 800 bp of 5'-flanking sequences upstream of the tld coding region were shown to drive an expression pattern indistinguishable from the wild-type pattern. A 423-bp fragment located within these sequences contains two DL binding sites and was shown to act as a silencer to mediate ventral repression. Point mutations in the sites abolish not only DNA binding but also ventral repression. We discuss a comparison of the DNA sequences from the zen and tld promoters and the possible mechanisms of transcriptional silencing.

Animals↗
PubMed1994

Paraneoplastic temporal lobe epilepsy with testicular neoplasm and atypical amnesia.

We report a patient who, at age 38, presented with temporal lobe seizures and an atypical memory disorder 3 years before the discovery of a testicular tumor. Detailed neuropsychological testing revealed a relatively isolated amnestic syndrome. The amnesia was atypical as the patient could retain information for hour-long periods, only to lose it later. Serologic studies revealed the presence of a circulating autoantibody that demonstrated an unusual affinity for the nucleolus of cerebral cortical neurons. Western blot analysis of cortical neurons revealed that this antibody reacted with proteins different from other previously identified paraneoplastic neurologic antigens (Hu, Yo, Ri). We believe this to be a case of paraneoplastic limbic encephalitis secondary to the testicular tumor. This patient presents unique characteristics with respect to the mode of presentation, features of the amnesia, and the presence of a circulating antibody with an unusual reactivity pattern.

Amnesia↗
PubMed1994

Plasticity in the adult human oligodendrocyte lineage.

Preoligodendrocytes have been described in cultures and tissue prints of adult human white matter (Armstrong et al., 1992). To characterize further these precursors of human oligodendrocytes, we have investigated whether they express genes playing a critical role in oligodendrocyte development. In the intact human brain, platelet-derived growth factor receptor alpha (PDGF alpha R) and myelin transcription factor 1 (MyTI) transcripts are expressed in 1-2% of cells of the oligodendrocyte lineage (OL), and clusters of such cells can be found in the periventricular region. Myelin basic protein transcripts containing exon 2 information (exon 2+ MBP), which are characteristic of the premyelinating stage, are detected in 15-20% of OL cells in vivo. When OL cells are separated from human white matter and allowed to regenerate in vitro, a much larger proportion of these cells express developmentally regulated genes, while exon 2- MBP and proteolipid protein (PLP) transcripts characteristic of mature OL cells appear transiently downregulated. Basic fibroblast growth factor (bFGF), even in the presence of PDGF, does not promote DNA synthesis in these cultured OL cells. Yet bFGF induces human oligodendrocytes to regenerate their processes rapidly in vitro and to express O4 antigens as well as exon 2+ MBP, MyTI, and PLP transcripts. While bFGF accelerates early regenerative processes, it also maintains high expression of exon 2+ MBP transcripts in OL cells for up to 2 weeks in vitro. In contrast, high levels of insulin in the absence of bFGF allow accumulation of exon 2- MBP and PLP transcripts in most OL cells at 2-3 weeks in vitro. We propose that the myelinated human brain harbors a small pool of precursors of oligodendrocytes and that growth factor-regulated phenotypic plasticity rather than mitogenic potential accounts for the regeneration of oligodendrocytes in the initial stages of demyelinating diseases such as multiple sclerosis.

Adolescent↗
PubMed1994

Retinal microvascular changes following bone marrow transplantation: the role of cyclosporine.

Three patients complained of deteriorating vision 16, 20 and 29 weeks following bone marrow transplantation (BMT) while receiving cyclosporine (CsA). Opthalmic examination revealed a marked microvascular retinopathy with multiple cotton-wool spots, macular stars and retinal oedema. These appearances could not be accounted for by the mild to moderate hypertension in two cases, the third patient being normotensive. Two of the patients had received total body irradiation (TBI) and cyclophosphamide (CY) as conditioning therapy for BMT as well as previous cranial irradiation for acute lymphoblastic leukaemia; one case with chronic myeloid leukaemia was conditioned with busulphan and CY. Withdrawal of CsA in two patients and reduction of dose in the third led to complete resolution of retinopathy and restoration of visual function. Previous reports have documented ischaemic fundus lesion in BMT recipients treated with CsA and TBI. Our findings suggest that CsA in association with busulphan can produce a similar retinopathy.

Adolescent↗
PubMed1994

Double-blind comparison of intranasal fluticasone propionate, 200 micrograms, once daily with 200 micrograms twice daily in the treatment of patients with severe seasonal allergic rhinitis to ragweed.

In a single-center, double-blind, crossover study of 90 subjects, fluticasone propionate aqueous nasal spray, 200 micrograms, once daily was compared with 200 micrograms twice daily in severe seasonal allergic rhinitis to ragweed. The mean percentage of days free of nasal itching and eye symptoms was significantly higher with twice daily fluticasone propionate (P = .004, P = .005, respectively). There were no significant differences between the two treatment groups for nasal blockage, rhinorrhea (runny nose), and sneezing. The median symptom scores for nasal itching were lower during twice daily treatment (P = .008) but there was no significant difference for the other symptoms. There were no significant differences between the groups in the use of rescue medication. Adverse events were infrequent, and similar in both groups. Most were considered unrelated to the treatment. Twice daily treatment with fluticasone propionate may be preferable for some patients with severe seasonal allergic rhinitis.

Administration, Intranasal↗