Search PubMed⌕ Search

Biomedical subjects

M Kelly

Publications and source records attributed to M Kelly.

At least 73 records · Page 4Linked to original sources
PubMed2000

High incidence of posttransplant lymphoproliferative disease in pediatric patients with cystic fibrosis.

A major cause of morbidity and mortality following lung transplantation is posttransplant lymphoproliferative disease (PTLD). In a retrospective cohort analysis of pediatric patients, we evaluated the risk factors associated with PTLD in 128 first-time lung transplant recipients from 1990 to 1997. The greatest risk factor for PTLD was a diagnosis of cystic fibrosis (CF). Of the 16 patients in our analysis who had PTLD, 13 had a diagnosis of CF (odds ratio [OR]: 5.8; confidence interval 95% [CI]: 1.6 to 21.4). Because of the high frequency of PTLD in patients with CF (13 of 61; 23%), we performed a retrospective cohort analysis in which patients with CF and PTLD were designated as cases and patients with CF and without PTLD served as controls. In patients with CF, the only risk factor associated with PTLD was two or more episodes of acute rejection within 3 mo after transplantation (OR: 11.0; 95% CI: 2.7 to 55.7). Age, recipient Epstein-Barr virus or cytomegalovirus status, induction with antilymphocyte globulin or antithymocyte globulin (ATG), or use of ATG or OKT3 for acute rejection episodes were not risk factors for PTLD. The high frequency of PTLD in the subgroup of patients with two or more episodes of graft rejection within 2 mo after lung transplantation was unexpected, and warrants further investigation in prospective clinical studies and basic laboratories.

Adolescent↗
PubMed2000

The effects of cocaine on basal and human chorionic gonadotropin-stimulated ovarian steroid hormones in female rhesus monkeys.

Cocaine stimulates gonadotropin (luteinizing hormone) release from the anterior pituitary in humans and in rhesus monkeys, but its acute effects on ovarian steroid hormones are unknown. The acute effects of cocaine and placebo on estradiol and progesterone were studied in 13 drug-naive female rhesus monkeys during the mid-follicular (days 8-10) and the mid-luteal (days 21-23) phases of the menstrual cycle. Each monkey was her own control under cocaine and placebo conditions. Samples for ovarian steroid hormone analysis were collected before and at 15-min intervals for 300 min after cocaine or placebo administration. In follicular phase females, estradiol levels increased significantly within 15 min after cocaine (0.8 mg/kg i.v.) administration (P <.008) but did not change after placebo administration. Estradiol remained significantly above baseline for 45 min (P <.002-0.02). In contrast, in mid-luteal phase females, estradiol did not change after cocaine or placebo administration. Basal progesterone levels did not change after cocaine or placebo administration in either mid-follicular or mid-luteal phase females. After hCG (500 I.U. i.m.) was administered to mid-luteal phase females, cocaine (0.4 and 0.8 mg/kg i.v.) and placebo administration did not increase or decrease estradiol or progesterone. One implication of these findings is that cocaine-induced increases in follicular phase estradiol levels could disrupt folliculogenesis and contribute to the menstrual cycle abnormalities observed during chronic cocaine self-administration.

Animals↗
PubMed1999

Cloning, chromosomal location, and expression analysis of murine Smarce1-related, a new member of the high-mobility 365 group gene family.

Proteins containing high-mobility group (HMG) domains are segregated into two major groups. Members of one group are identified by the presence of more than one HMG domain that binds to DNA without sequence specificity, and they are usually ubiquitously expressed. In contrast, members of the other group possess a single HMG domain with high affinity to specific DNA sequences. Generally, members of the second group resemble classic tissue-specific transcriptional regulators. In contrast, Smarce1/BAF-57 is a ubiquitously expressed, novel protein with a single HMG domain that displays nonspecific DNA-binding characteristics. Additionally, as a core subunit of the mammalian SWI/SNF-like transcriptional activator complex, Smarce1/BAF-57 is also the first member of the HMG protein family that was reported to contain a kinesin-like coiled-coil (KLCC) domain. Here we report the cloning, as well as the chromosomal and phylogenetic analysis, of a novel mammalian protein that is structurally related to Smarce1, termed Smarce1-related (Smarce1r). The unique arrangement of an HMG with a KLCC domain shared with Smarce1/BAF-57 suggests a similar, albeit still unknown, function in chromatin assembly as part of a mammalian SWI/SNF-like complex. The linkage of a single nonspecific DNA-binding HMG domain with a KLCC domain makes both proteins the founding members of a third group of HMG proteins.

Amino Acid Sequence↗
PubMed1999

Molecular cloning and phylogenetic analysis of the small cytoplasmic RNA from Listeria monocytogenes.

A molecular cloning strategy has been designed to isolate the gene that encodes the small cytoplasmic RNA (scRNA) component of bacterial signal recognition particles. Using this strategy a putative Listeria monocytogenes scRNA lambda gt11 recombinant clone was isolated. A previously described complementation assay developed to genetically select functional homologues of 4.5S RNA and scRNA of bacteria confirmed that the lambda gt11 recombinant clone isolated encoded for the scRNA from L. monocytogenes. A secondary structure for this scRNA is proposed and a phylogenetic comparison of the 276 base L. monocytogenes scRNA with previously characterised Gram-positive bacterial scRNAs is also presented.

Base Sequence↗
PubMed1999

Improved bladder function after prophylactic treatment of the high risk neurogenic bladder in newborns with myelomentingocele.

PURPOSE: High pressure dyssynergic voiding may result in irreversible damage to the urinary tract. Prophylactic therapy in the form of clean intermittent catheterization and anticholinergic medication may significantly decrease the incidence of upper urinary tract deterioration. Whether prophylactic therapy in the high risk bladder may also lead to improved long-term bladder dynamics prompted us to study the effect of early versus late treatment of bladder hypertonicity and detrusor-sphincter dyssynergia on the ultimate need for bladder augmentation. MATERIALS AND METHODS: We retrospectively reviewed urological outcomes in patients with myelodysplasia who were at risk for urological deterioration within year 1 of life based on bladder sphincter dyssynergia and/or high filling or voiding pressure. We recorded the dates when high risk voiding dynamics were initially observed, and when intermittent catheterization and anticholinergic therapy were initiated. Patients in whom treatment began at the time a high risk profile was noted (prophylactic group seen between 1985 and 1990) were compared to controls with the same high risk voiding parameters who did not receive early therapy (observation group seen between 1978 and 1984 with therapy instituted 1 year or longer after high risk was noted). The number of augmentations performed in each group was indexed to the total number of years of followup in the 2 populations, respectively. Patients with less than 2 years of followup were excluded from further analysis. RESULTS: Of the 45 patients at risk clean intermittent catheterization and anticholinergic medication were immediately initiated in 18, while 27 were treated expectantly. Patients in the observation group were followed an average of 4.1 years (range 1.1 to 14) before clean intermittent catheterization and anticholinergic medication were started. Of the 27 children treated expectantly 11 (41%) required augmentation, whereas only 3 of the 18 (17%) treated prophylactically required enterocystoplasty. When the number of augmentations was indexed to total years of followup in each of the 2 groups (296 versus 156 years) patients in the expectant group were nearly twice as likely to require augmentation. CONCLUSIONS: Identification and early proactive treatment of the high pressure, dyssynergic lower urinary tract significantly decreases the need for bladder augmentation as children with neurogenic bladder secondary to myelomeningocele mature.

Adolescent↗
PubMed1999

New nitrogenous bisabolene-type sesquiterpenes from a micronesian marine sponge, axinyssa species

Chemical investigation of an Axinyssa species of sponge collected at Yap Island afforded three new nitrogenous sesquiterpenes, 1-3, together with the known compound 3-formamidotheonellin (4). The structures of compounds 1, 3, and 4 were confirmed by spectroscopic methods, and compound 2 was tentatively identified by comparison of its (1)H and (13)C NMR data with those of 1, 3, and 4 and (1)H decoupling experiments.

Journal Article↗
PubMed1999

Do iron and vitamin C co-supplementation influence platelet function or LDL oxidizability in healthy volunteers?

OBJECTIVE: To examine the effect of co-supplementation with iron and vitamin C on antioxidant status, platelet function and low density lipoprotein oxidation in normal healthy volunteers. DESIGN: The study was carried out with two groups of 20 subjects each acting as their own control, comparing presupplemention with postsupplemention. One group was supplemented with iron and the RDA level of vitamin C and the second group with iron and 260 mg/d vitamin C. SETTING: The International Antioxidant Research Centre, The Guy's, King's College and St Thomas's School of Biomedical Science, Guy's Campus, London. SUBJECTS: Forty normal healthy volunteers, recruited from the staff of the Medical School and Hospital in which two volunteers withdrew during the study. INTERVENTIONS: Subjects in both studies were randomly assigned to one of two groups (5 males and 5 females group) and received supplements containing iron (14 mg/d) and either 60 mg/d (Group A) or 260 mg/d (Group B) vitamin C for 12 wk. Blood samples were taken at 6 wk and 12 wk, and prior to supplementation and analysed for iron and antioxidant status (transferrin bound iron, vitamin C and E, and beta-carotene levels) in both studies. Samples from the first study were analysed for the susceptibility of LDL isolated from plasma to Cu2+-induced oxidation and samples from the second for platelet function. RESULTS: Transferrin-bound iron was significantly increased (P < 0.05) at 12 wk, in Group A subjects (from 14.9+/-5.3 micromol/1 to 19.5+/-2.3 micromol/l; mean+/-s.d.; n=19), whereas those in Group B showed a significant increase (P < 0.05) after 6 wk (from 15.8+/-4.5 micromol/l to 20.4+/-6.6 micromol/l; n = 19) which decreased at 12 wk (16.3+/-5.0 micromol/l). Plasma total ascorbate significantly increased from an initial level of 59.3+/-21.3 micromol/l to 87.6+/-29.0 micromol/l after 6 wk and 81.7+/-11.4 micromol/l after 12 wk following the Group B supplementation, but only after 12 wk in Group A (from 64.0+/-24.8 micromol/l to 77.2+/-13.2 micromol/l). Plasma alpha-tocopherol concentrations were significantly increased after 6 wk and 12 wk with both levels of supplementation (from 24.2+/-5.71 micromol/l Group A and 23.4+/-5.3 micromol/l Group B to 26.3+/-5.5 micromol/l and 25.71+/-4.7 micromol/1 respectively at 12wk). The mean lag phase to oxidation of low density lipoprotein (LDL) was significantly increased in subjects in Group B after 12 wk ingestion of iron and 260 mg vitamin C (from 80.0+/-14.8 min to 97.2+/-16.9 min; n = 9). Platelet sensitivity to ADP-induced aggregation was significantly decreased (P < 0.05) by 12 wk in Group A (from EC50 2.3 < or = 1.3 microM to 3.7+/-2.2 microM; n = 10), whereas those receiving higher vitamin C showed a significant decrease (P < 0.05; from EC50 1.9+/-0.6 microM to 3.1+/-1.8 microM) after 6wk which subsequently increased towards presupplemental levels (2.6+/-1.6 microM). Platelets from the latter subjects showed a significant reduction in ADP-induced ATP secretion at both 6wk and 12 wk. CONCLUSION: The results show modest beneficial effects on LDL oxidation and platelet function following supplementation with iron and vitamin C. No evidence for pro-oxidant effects was observed.

Adenosine Diphosphate↗
PubMed1999

Vascular surgical society of great britain and ireland: review of out-of-hours vascular procedures in a tertiary vascular unit

BACKGROUND: The aim of this study was to review out-of-hours vascular procedures in a tertiary vascular unit. METHODS: The vascular emergencies that presented outside normal working hours (17. 00 to 08.00 hours) in a vascular unit between January and June 1998 were reviewed. Only cases considered to be life or limb threatening and requiring urgent surgical or radiological intervention were assessed. RESULTS: The Table shows that a significant number of vascular emergencies was performed out of hours in one unit. This was, in part, due to an increase in the number of tertiary referrals, which represented 57 per cent of all emergency procedures. Reasons for the tertiary referrals were: no consultant vascular surgeon on call (33 per cent), no consultant interventional radiologist on call (26 per cent), lack of intensive care beds (30 per cent) and complex procedure (11 per cent). The overall mortality rate of patients referred in this period was 15 per cent. The unit has three consultant vascular surgeons, two consultant interventional radio- logists and one vascular specialist registrar. CONCLUSION: The significant increase in out-of-hours vascular emergencies, both surgical and radiological, has placed an enormous demand on senior members of the team. In addition, it has had a significant impact on the unit's elective admissions and waiting lists, in particular those for routine general surgery. To support the growth in complex emergency referrals, senior vascular fellows in both vascular surgery and radiology have been appointed and proposals are underway to restructure local vascular services.

Journal Article↗
PubMed1999

NMR studies on the 46-kDa dimeric protein, 3,4-dihydroxy-2-butanone 4-phosphate synthase, using 2H, 13C, and 15N-labelling.

3,4-Dihydroxy-2-butanone 4-phosphate synthase catalyses the release of C-4 from the substrate, ribulose phosphate, via a complex series of rearrangement reactions. The cognate ribB gene of Escherichia coli was hyperexpressed in a recombinant E. coli strain. The protein was shown to be a 46-kDa homodimer by hydrodynamic analysis. A variety of protein samples labelled with different grades of 13C, 15N and 2H, i.e. one with 100% 2H and 15N, one with 75% 2H, 99% 13C, 15N, and one with 100% 2H, 99% 13C,15N were prepared. Despite the large molecular size, 2- and 3-dimensional NMR spectra of reasonable quality were obtained. Attempts at the assignment of individual 13C, 15N and 1H signals show, in principle, the feasibility of structure determination. The number of NMR signals shows unequivocally that the homodimeric protein obeys strict C2 symmetry.

Base Sequence↗
PubMed1999

Normal urodynamics in patients with bladder exstrophy: are they achievable?

PURPOSE: Urodynamic study was performed in patients with exstrophy to determine the effect of bladder neck reconstruction and the ability to achieve normal urodynamics following surgery. MATERIALS AND METHODS: A total of 30 exstrophy cases at different stages of reconstruction were retrospectively reviewed in terms of bladder capacity, compliance, stability and presence of detrusor contractions following urodynamic study. RESULTS: Bladder capacity increased from a third predicted volume for age to half after reconstruction. Approximately 80% of patients had compliant and stable bladders before bladder neck reconstruction. Following bladder neck reconstruction approximately half of the patients maintained normal compliance with a smaller number maintaining normal stability. A quarter of patients maintained normal filling dynamics following bladder neck reconstruction, and 19% maintained normal filling and voiding dynamics after reconstruction. CONCLUSIONS: The majority of closed exstrophy bladders have normal filling dynamics before bladder neck reconstruction. Compliance and stability are impaired following bladder neck reconstruction. Approximately 25% of patients with exstrophy may maintain normal detrusor function following reconstruction. However, less invasive alternatives to the Young-Dees-Leadbetter bladder neck reconstruction should be sought.

Adolescent↗
PubMed1999

Solution structure of the receptor tyrosine kinase EphB2 SAM domain and identification of two distinct homotypic interaction sites.

The sterile alpha motif (SAM) is a protein interaction domain of around 70 amino acids present predominantly in the N- and C-termini of more than 60 diverse proteins that participate in signal transduction and transcriptional repression. SAM domains have been shown to homo- and hetero-oligomerize and to mediate specific protein-protein interactions. A highly conserved subclass of SAM domains is present at the intracellular C-terminus of more than 40 Eph receptor tyrosine kinases that are involved in the control of axonal pathfinding upon ephrin-induced oligomerization and activation in the event of cell-cell contacts. These SAM domains appear to participate in downstream signaling events via interactions with cytosolic proteins. We determined the solution structure of the EphB2 receptor SAM domain and studied its association behavior. The structure consists of five helices forming a compact structure without binding pockets or exposed conserved aromatic residues. Concentration-dependent chemical shift changes of NMR signals reveal two distinct well-separated areas on the domains' surface sensitive to the formation of homotypic oligomers in solution. These findings are supported by analytical ultracentrifugation studies. The conserved Tyr932, which was reported to be essential for the interaction with SH2 domains after phosphorylation, is buried in the hydrophobic core of the structure. The weak capability of the isolated EphB2 receptor SAM domain to form oligomers is supposed to be relevant in vivo when the driving force of ligand binding induces receptor oligomerization. A formation of SAM tetramers is thought to provide an appropriate contact area for the binding of a low-molecular-weight phosphotyrosine phosphatase and to initiate further downstream responses.

Amino Acid Motifs↗
PubMed1999

Deep brain stimulation of the ventral intermediate nucleus of the thalamus for control of tremors in Parkinson's disease and essential tremor.

The beneficial effects of ventral intermediate nucleus (VIM) stimulation were evaluated in 20 patients with tremor refractory to medical therapy. Thalamic stimulation is a non-ablative procedure which has the advantage of a reversible, non-destructive lesion. Eleven patients [7 with Parkinson's disease (PD) and 4 with essential tremor (ET)] received unilateral VIM implantation, while 9 patients had staged bilateral VIM implantation (4 with PD, 5 with ET). PD patients showed a significant improvement in contralateral arm and leg rest tremor and ipsilateral leg rest tremor (p < 0.02) at a mean follow-up period of 16.2 +/- 7.0 months. Patients with PD did not demonstrate any significant decrease in medication use at follow-up. ET patients demonstrated significant improvement in postural and action tremor in the contralateral arm (p < 0.001), but no significant improvement in the contralateral leg tremor at follow-up. Significant improvements were also seen in ET patients in the Clinical Rating Scale for Tremor (p < 0.001) with respect to several activities of daily living at a mean follow-up of 14.9 +/- 8. 1 months. Deep brain stimulation is a safe and effective treatment for severe tremor refractory to medications. It is a highly effective, reversible, adaptable, and predictable procedure which avoids the complication of cognitive deficit seen in patients with bilateral thalamotomies.

Aged↗