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S O'Shea

Publications and source records attributed to S O'Shea.

At least 19 recordsLinked to original sources
PubMed2006

Characterization of the three Arabidopsis thaliana RAD21 cohesins reveals differential responses to ionizing radiation.

The RAD21/REC8 gene family has been implicated in sister chromatid cohesion and DNA repair in several organisms. Unlike most eukaryotes, Arabidopsis thaliana has three RAD21 gene homologues, and their cloning and characterization are reported here. All three genes, AtRAD21.1, AtRAD21.2, and AtRAD21.3, are expressed in tissues rich in cells undergoing cell division, and AtRAD21.3 shows the highest relative level of expression. An increase in steady-state levels of AtRAD21.1 transcript was also observed, specifically after the induction of DNA damage. Phenotypic analysis of the atrad21.1 and atrad21.3 mutants revealed that neither of the single mutants was lethal, probably due to the redundancy in function of the AtRAD21 genes. However, AtRAD21.1 plays a critical role in recovery from DNA damage during seed imbibition, prior to germination, as atrad21.1 mutant seeds are hypersensitive to radiation damage.

Arabidopsis↗
PubMed2005

Therapeutic, prophylactic, and preresection applications of laparoscopic gastric and biliary bypass for patients with periampullary malignancy.

BACKGROUND: Laparoscopic bypass surgery for the palliation of gastric and biliary obstruction is associated with a rapid recovery. This study aimed to extend its application to other aspects in the management of patients with periampullary cancer. METHODS: Between 2001 and 2004, 21 patients (median age, 68 years) underwent laparoscopic gastric (n = 8), biliary (n = 5), and combined gastric and biliary (n = 8) bypass. In addition to its therapeutic role (n = 12), indications included a concomitant prophylactic gastric (n = 3) and biliary (n = 2) bypass as well as pre- 1 Whipple's relief of deep jaundice at the time of staging laparoscopy (n = 3). Construction of the biliary bypass to the gallbladder (n = 11) or bile duct (n = 2) was based on preoperative imaging. RESULTS: All procedures were completed laparoscopically. The median operating times for gastric, biliary, and combined bypass were 75, 60, and 130 min, respectively. The addition of a prophylactic bypass did not significantly prolong the operating time, as compared with a single therapeutic bypass. One patient died postoperatively of aspiration pneumonia. The postoperative hospital stay (median, 4 days) was not significantly influenced by the type of bypass. No recurrence of or new obstructive symptoms developed during the follow-up period after a therapeutic or prophylactic bypass. CONCLUSIONS: Applications of laparoscopic gastric and biliary bypass can safely be expanded to include a prophylactic role and preresection relief of obstructive jaundice. Prophylactic bypass surgery does not prolong operating time or hospital stay significantly and prevents future onset of obstructive symptoms.

Adult↗
PubMed2005

Genotyping of B and non-B subtypes of human immunodeficiency virus type 1.

Current HIV-1 genotyping assays were developed using subtype B viruses prevalent in Western countries. It is not clear whether these assays are appropriate for use among African patients, who are likely to be infected with non-B subtypes. We evaluated the Bayer TRUGENE HIV-1 genotyping (TG) assay using prospectively collected samples from HIV-1-infected individuals who acquired infection in either sub-Saharan Africa or the West (Europe, North America, and Australia). Plasma samples from 208 individuals with an HIV-1 viral load of >1,000 copies/ml were tested using version 1 primers supplied with the TG assay. If these failed, an alternative primer set version 1.5 was used. Of the 208 individuals, the likely origin of infection was Africa (n = 104), Western (n = 87) and "Others" (i.e., all other geographic locations or origin not certain; n = 17). Among the three groups, the version 1 primers were successful in 85 (82%), 77 (89%), and 13 (76%) individuals, respectively (P = 0.1). Of the remaining 32 samples, 30 were successfully amplified by using the version 1.5 primers. HIV-1 subtypes deduced from the reverse transcriptase sequences correlated with the likely origin of infection: Africa (28A, 3B, 33C, 13D, 6G, 4J, 2K, 5CRF01_AE, and 10CRF02_AG), Western (86B and 1K), and Others (1A and 16B). The success of the version 1 primers correlated with viral load (P < 0.014) and not with HIV-1 subtypes. A protocol based on version 1 primers, followed by 1.5 primers, was successful in sequencing 99% of the samples in this cohort.

Adolescent↗
PubMed2004

Pilot scheme for performance assessment of HIV-1 genotypic resistance testing in the UK.

HIV-1 drug susceptibility testing by genotypic methods is now widespread in the UK and it is thus important to determine the reproducibility of such investigations. A pilot study was carried out to determine the reproducibility between laboratories of genotypic testing by nucleotide sequencing of patient samples, and to compare the interpretations of the results provided to the clinicians. Samples were distributed between the participating laboratories. Eight laboratories, using three different methods, sequenced four samples. Nucleotide sequence and reports were collated and compared by one laboratory. Where sequencing data were obtained > 99% concordance was observed for nucleotide designations. No discordances in nucleotide sequencing were found in positions associated with drug resistance. However, there were considerable differences between the laboratories in the interpretation of some of the mutations with respect to their effect on drug susceptibility. This study emphasises the variability in the available interpretation systems, and the importance of joint laboratory-clinical discussion in making decisions about treatment options.

Data Interpretation, Statistical↗
PubMed2003

Laparoscopic reduction of an ileoileal intussusception and resection of an inverted Meckel's diverticulum in an adult.

Intussusception occurs commonly in children, but rarely is observed in adults. Whereas the hydrostatic pressure of a contrast enema often proves diagnostic as well as therapeutic in infants and children, resection usually is required for an underlying bowel pathology in older children and adults. Conventionally, the resection is accomplished at laparotomy. We report the case of a 20-year-old woman who presented with diarrhea and vomiting of 1 week duration. She was found unexpectedly to have intussusception on abdominal ultrasonography. The intussusception was laparoscopically reduced, and a segment of the middle small bowel that harbored an inverted Meckel's diverticulum was resected laparoscopically, after which an intracorporeal anastomosis was fashioned. The ileus resolved on postoperative day 4, and the patient was discharged from hospital on postoperative day 5. The role of the laparoscopic approach in the management of intussusception is discussed.

Adult↗
PubMed2001

Expression of glycine receptors in rat sensory neurons vs. HEK293 cells yields different functional properties.

Many structure-function studies of the glycine receptor (GlyR), and other ligand-gated ion channels, use somatic cell lines or Xenopus oocytes as expression systems. Using a polyethylenimine-based technique, we transfected GlyR cDNA into primary cultures of rat dorsal root ganglion (DRG) neurons. We then compared the functional properties of wildtype and a mutant GlyR expressed in DRG neurons with HEK 293 cells. The glycine sensitivity of the wildtype GlyR was nearly identical for the two cell types. The mutant GlyR has an arginine for glutamine substitution at position 271 (R271Q), which results in low glycine sensitivity relative to wildtype receptors expressed in HEK cells. This point mutation is associated with startle disease (hyperekplexia) in humans. Mutant GlyR expression in DRG neurons resulted in a significantly lower glycine sensitivity than was seen in HEK cells. This supports the idea that neuron-specific post-translational modifications may be important for determining receptor function.

Animals↗
PubMed2001

Effects of in vivo heregulin beta1 treatment in wild-type and ErbB gene-targeted mice depend on receptor levels and pregnancy.

Mice heterozygous (+/-) for either heregulin (HRG), ErbB2, or ErbB3 were created by gene targeting, resulting in the loss of one functional gene copy and an associated decrease in targeted protein. We examined the in vivo activity of recombinant HRG peptide, rHRG beta1 (amino acids 177 to 241), in the three heterozygous mouse lines and in wild-type (WT) mice, both pregnant and nonpregnant. Nonpregnant WT and HRG(+/-) mice of both sexes were sensitive to rHRG beta1 treatment as evidenced by a high mortality rate associated with abdominal enlargement and parietal cell loss. However, pregnant WT mice and ErbB2 and ErbB3 heterozygous mice treated with rHRG beta1 were less affected, with significantly lower mortality rates and a less severe abdominal phenotype. Histological analysis revealed extensive breast ductal hyperplasia in females of all genotypes after rHRG beta1 treatment. Hyperplasia of other epithelial tissues such as the pancreas and intestine and the growth of cardiac nerve bundles were also observed, independent of sex.

Animals↗
PubMed2001

Guidelines for the management of HIV infection in pregnant women and the prevention of mother-to-child transmission.

AIMS OF THE GUIDELINES: These guidelines, drawn up by a multidisciplinary group of clinicians and lay workers active in the management of pregnant women infected with HIV, aim to give up-to-date information on interventions to reduce the risk of mother to child transmission of the virus. The evidence on the use of interventions to prevent mother to child transmission of HIV has been graded according to the strength of the data as per the definitions of the US Agency for Health Care Policy and Research [1]. Weighted evidence on the use of combination antiretroviral therapy (ART) for the treatment of HIV infection per se is presented in the BHIVA guidelines for adults [2,3]. The highest level evidence (i.e. randomised controlled trials (RCTs) or large, well conducted meta-analyses) is only available for formula feeding, prelabour caesarean section and zidovudine monotherapy. The need to treat mothers for HIV infection has led to the widespread use of ART in pregnancy which in turn results in new questions such as how to deliver when the mother, on therapy, has no detectable plasma viraemia with the most sensitive assays. In addressing many common and/or difficult clinical scenarios in the absence of 'best evidence' the guidelines rely heavily on 'expert opinion'. Recommendations for management are given in the section on clinical scenarios, and summarized in Table 3. An expanded version of these guidelines with an appendix on safety and toxicity data is available on the BHIVA website http://www.bhiva.org. The authors are available to discuss individual cases.

Adult↗
PubMed2001

Antiretroviral therapy for HIV-2 infected patients.

OBJECTIVES: To evaluate clinical and RNA load response to antiretroviral therapy amongst patients infected with HIV-2 and to study the development of drug resistance. METHODS: Seven HIV-2 seropositive patients were monitored with clinical examination, CD4 cell count and HIV-2 viral RNA load. Viruses from four subjects were genotyped and in vitro recovery of virus by co-cultivation with PBMCs and HVS T-cells was attempted. Viruses isolated from two subjects were assayed for phenotypic antiviral resistance. The main outcome measures were the relationship between disease stage, viral load, CD4 cell count, viral subtype and the clinical course of HIV-2 infection and the effect of combination antiretroviral therapy on disease progression, CD4 cell count, HIV-2 RNA viral load and drug resistance. RESULTS: The median time of follow-up was 3 years (range 0-8 years). Three patients had AIDS, and one had symptomatic disease. Of the four patients genotyped, three were infected with HIV-2 subtype B and one with subtype A. Viraemia was detectable only at CD4 counts of less than 300 x 10(6)/ml. Two patients with high viral loads failed to respond to antiretroviral therapy although their treatment may not have been optimal. One developed in vitro phenotypic antiviral resistance. The genotype of this patient's viral reverse transcriptase is being analysed. CONCLUSIONS: In contrast to HIV-1, HIV-2 RNA levels were often undetectable despite advanced disease and low CD4 cell counts. However, HIV-2 was clearly capable of causing CD4 cell depletion resulting in symptomatic disease. The principles of highly active antiretroviral therapy seem to apply to HIV-2 and suboptimal therapy may lead to drug resistance. The timing of therapy initiation, monitoring of response and the measurement of resistance remain unresolved issues and conclusions cannot be extrapolated from HIV-1.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Problems in the interpretation of HIV-1 viral load assays using commercial reagents.

During routine monitoring of human immunodeficiency virus (HIV) viral load, two problems arose. First, a number of patients, the majority being African, were found to have low viral loads by the Chiron branched-chain DNA assay in conjunction with low CD4(+) cell numbers. In order to determine whether this was due to failure of the branched-chain DNA assay to detect non-B subtypes of HIV, selected samples were subtyped and HIV RNA quantified by branched-chain DNA, NASBA, and the Roche Monitor RT-PCR assay. Twenty-eight (97%) of 29 Africans were infected with a non-B subtype of HIV and 15 (93.7%) of 16 non-Africans with subtype B. Twenty-three samples had a low viral load by branched-chain DNA, which was confirmed by the NASBA and RT-PCR assays. All three assays detected B and non-B subtypes with similar efficiency; NASBA failed to detect HIV RNA in a small number of non-B samples. Discrepancies between viral load and CD4(+) cell numbers did not appear therefore to be related to subtype. Second, while quantification of HIV RNA was being conducted using version 2 of the branched-chain DNA assay (lower detection limit 500 HIV RNA copies/ml) the manufacturers had developed a more sensitive assay and a comparative evaluation was therefore conducted. In approximately 30% of samples the viral load was up to 10 times higher with the more sensitive assay. These experiences emphasise the importance of close collaboration between the clinic and the laboratory.

CD4 Lymphocyte Count↗
PubMed2000

Renal medullary carcinoma: sonographic, computed tomography, magnetic resonance and angiographic findings.

Renal medullary carcinoma is a recently described, highly aggressive tumour, occurring predominantly in young patients of African descent with sickle cell trait (SCT). All have been metastatic at surgery. Surgery, radiotherapy and chemotherapy do not appear to alter the course of the disease. The survival time is very short. Presentation is usually with haematuria, abdominal pain and weight loss. Forty-nine patients have been reported from the USA, of these 47 were African/Americans. The reports have mostly appeared in pathology journals. On review of the imaging findings reported in the radiological journals, it becomes apparent that it is possible for a radiologist to suggest a specific diagnosis in the appropriate demographic and clinical setting. Here the first British patient of Afro-Caribbean decent in whom a pre-operative diagnosis was suggested on the imaging findings of a centrally located renal pelvic tumour, encasing the pelvis on a background of SCT in a 28-year-old is described. It is expected that a high index of suspicion in the appropriate clinical setting may lead to earlier diagnosis, treatment and survival of patients. The patient is alive and reasonably well 9 months after surgery. The full range of imaging findings in renal medullary carcinoma are described.

Adult↗
PubMed1999

Bronchial smooth muscle hypoplasia in mouse embryonic lungs exposed to a laminin beta1 chain antisense oligonucleotide.

We used an antisense oligonucleotide (ODN) to inhibit laminin (LM) beta1 chain synthesis in mouse embryonic lung explants and cell cultures. The ODN spanned 17 bases located 13 bases downstream the initiation codon and contained phosphorothioate and C-5 propynyl pyrimidine modifications. Penetration of the ODN into the lung explants was confirmed by fluorescein isothiocyanate (FITC) tagging. 50 microM of antisense ODN decreased LM beta1 chain synthesis by 82+/-6.9% with no significant changes in the synthesis of other LM chains. The same antisense probe but without C-5 propynyl pyrimidine modification, another 17-mer ODN complementary to the LM beta1 initiation codon, and a 17-mer ODN complementary to the LM alpha1 initiation codon had no antisense activity. Lung explants exposed to the active LM beta1 antisense ODN showed decreased LM-1 and collagen type IV deposition at the epithelial-mesenchymal interface and an arrest in bronchial smooth muscle (SM) development. Histological examination and cell motility assays suggested that this arrest was due to impaired spreading and migration of SM cell precursors over the defective basement membrane (BM). Our studies indicate that beta1-chain containing LMs play a role in bronchial myogenesis.

Animals↗
PubMed1999

Human herpesvirus 8: seroepidemiology among women and detection in the genital tract of seropositive women.

An indirect IFA to detect antibodies against latent nuclear antigens of human herpesvirus 8 (HHV-8) was used to determine the prevalence of HHV-8 antibodies in 169 women attending a sexually transmitted diseases clinic and a human immunodeficiency virus (HIV) clinic at a London hospital. Nested polymerase chain reaction was used to detect HHV-8 DNA in 93 blood samples and 89 cervical brush scrapes (CBS). Another 96 CBS from women attending a colposcopy clinic were also analyzed. The overall seroprevalence of HHV-8 was 18.3%. The seroprevalence was higher among women born in Africa (24.7%) than among women born elsewhere (11.5%; P=.06) and was independent of HIV serostatus. HHV-8 DNA was detected in 3 CBS and 6 peripheral blood samples from 11 HHV-8-seropositive women but not in CBS from 78 seronegative women, 96 women from the colposcopy clinic, or in blood samples from 82 seronegative women.

Africa↗