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Biomedical subjects

M Kelly

Publications and source records attributed to M Kelly.

At least 19 recordsLinked to original sources
PubMed2000

Mutational analysis of basic residues in the rat vesicular acetylcholine transporter. Identification of a transmembrane ion pair and evidence that histidine is not involved in proton translocation.

The function of positively charged residues and the interaction of positively and negatively charged residues of the rat vesicular acetylcholine transporter (rVAChT) were studied. Changing Lys-131 in transmembrane domain helix 2 (TM2) to Ala or Leu eliminated transport activity, with no effect on vesamicol binding. However, replacement by His or Arg retained transport activity, suggesting a positive charge in this position is critical. Mutation of His-444 in TM12 or His-413 in the cytoplasmic loop between TM10 and TM11 was without effect on ACh transport, but vesamicol binding was reduced with His-413 mutants. Changing His-338 in TM8 to Ala or Lys did not effect ACh transport, however replacement with Cys or Arg abolished activity. Mutation of both of the transmembrane histidines or all three of the luminal loop histidines showed no change in acetylcholine transport. The mutant H338A/D398N between oppositely charged residues in transmembrane domains showed no vesamicol binding, however the charge reversal mutant H338D/D398H restored binding. This suggests that His-338 forms an ion pair with Asp-398. The charge neutralizing mutant K131A/D425N or the charge exchanged mutant K131D/D425K did not restore ACh transport. Taken together these results provide new insights into the tertiary structure in VAChT.

Acetylcholine↗
PubMed2000

An evaluation of mattresses and mats in two dairy units.

In order to investigate the relative merits of mats and mattresses in terms of cow comfort, production and performance, 29 cows were housed on ethylethene vinyl acetate (EVA) mats and 29 on mattresses of loose rubber crumb with a polypropylene cover, at each of two similar dairy units (SAC Auchincruive and Myerscough). Both mats and mattresses were newly installed at the start of the trial. The cows were housed in the autumn after calving. Milk yield was recorded daily. Cows were weighed and scored for body condition, locomotion, dirtiness and hock and knee injury at fortnightly intervals. Feed offered was recorded daily and refusals were weighed weekly. Monthly milk records of milk yield, milk composition and somatic cell count data were available for both herds. In addition, 24 h behavioural observations of 15 core cows in each group were made at weeks 0, 2, 4, 6, 8, 16, and 32 post-housing. There was no difference between cows on mats and mattresses in milk yield, composition or quality; in feed intake; in weight loss or body condition score; in severe hock or knee injury, or in the incidence of lameness. Cows on mattresses tended to have slightly higher total dirtiness scores than those on mats (7.06 vs. 6.95, P=0.074) and had dirtier udders (mattress, 7.50 vs. mat, 6.52, P<0.05). However, over the whole housing period, cows on mattresses spent longer feeding, ruminating and lying and a greater proportion of their lying time was spent ruminating. They spent less time standing doing nothing (idling) than cows on mats and less time idling in cubicles. Cows on mattresses appeared to adapt to housing more quickly than those on mats. Overall, neither mat nor mattress gave advantages in terms of production or performance, cows were slightly cleaner on mats but behavioural indices suggest that cow comfort was greater on mattresses.

Journal Article↗
PubMed2000

Acute effects of nalmefene on LH, prolactin, and testosterone in male rhesus monkeys.

The effects of the long-acting opioid antagonist, nalmefene [17-N-cyclopropylmethyl-3,14-beta-dihydroxy-4, 5-alpha-epoxy-6-methylene morphinan hydrochloride] on LH, T, and prolactin release in rhesus monkeys are unknown. The acute effects of nalmefene (0.01 and 0.10 mg/kg, IV) or placebo on LH, PRL, and T were studied, and samples were collected at 10-min intervals for 360 min to permit cluster analysis of pulsatile release patterns. LH increased significantly within 30 min after nalmefene, and remained significantly above baseline levels for 50 to 60 min (p < 0.05). Testosterone increased significantly within 70 to 80 min after nalmefene, and remained significantly above baseline for 60 min (p < 0.05). Although nalmefene antagonizes opioid agonists for 6-8 h, inhibitory feedback by testosterone appeared to limit the duration of its antagonism of endogenous opioid inhibition of LHRH and stimulation of LH. Nalmefene did not change LH or PRL pulse frequency or amplitude significantly in comparison to placebo administration.

Animals↗
PubMed2000

Extrafamilial sexual abuse: treatment for child victims and their families.

OBJECTIVES: To decrease the emotional distress of child victims of extrafamilial sexual abuse (ESA) and their families. To provide crisis intervention, individual and group treatment in response to an expressed need in the community. To pilot the use of group treatment for child victims of ESA under age 10. METHOD: This discussion describes intervention with a sample of 246 child victims, ages 2-14 years, and 323 parents who participated in the program from 1984 to 1991. This pilot project operated at a university medical facility and was located off campus in an outpatient child abuse center. Priority was given to child victims under age 7. Child victims and their families were evaluated after investigative interviews by law enforcement agencies were completed. A treatment plan was developed based on clinical assessment. Families participated in crisis counseling, individual treatment for the child victim and/or parent, Children's Treatment Groups, Parent Support Groups, or were referred to other resources. Clinical assessment of treatment progress included weekly case review by child and parent therapists, video analysis and observation of Children's Treatment Group sessions, consultation with parents and collateral contacts. RESULTS: A family approach and services for parents in addition to intervention for child victims were determined to be key components in facilitating recovery. Clinical observations and client feedback showed positive outcomes for child victims and parents with crisis counseling, Children's Treatment groups, and Parent Support Groups. The extent of intervention ranged from one session to 24 months with an average participation of 6-9 months. Follow up surveys were returned by parents for 48 child victims and results are reported. Themes, parallels in responses, and recovery factors for child victims and parents are discussed. CONCLUSIONS: The need for intervention and a community-based program was demonstrated by (1) the significant disruption in functioning that occurred for child victims of ESA and their families, (2) the risk for long term sequelae, (3) the high incidence of extrafamilial sexual abuse, and 4) the consistent, large number of requests for services. Family-centered crisis services, Children's Treatment Groups, and Parent Support Groups can be effectively based at child advocacy centers, out patient care clinics, or other community agencies. The results of formal outcome measures and longitudinal studies is needed to determine how child victims and parents benefit from specific treatment modalities and to better guide the use of limited resources.

Adolescent↗
PubMed2000

Design of copper-based anti-inflammatory drugs.

It has been shown that the inflammation associated with rheumatoid arthritis can be reduced using copper complexes. In order to improve the bioavailability of copper and hence efficacy of these complexes we have synthesized three different series of ligands, each having different characteristics. Thermodynamic results for copper(II) complexes for these polyamino, diaminodiamido and triaminodiamido ligands are presented. The polyamino ligands form the most stable complexes in vivo but tissue distribution studies in mice show that [Cu(3,6,9,12-tetraazatetradecanedioate)] is excreted rapidly, unchanged in the urine. The diamino ligand complexes are much less stable than their polyamino analogues and animal studies using [Cu(N,N'-bis[2-(dimethylamino)ethyl]-ethanediamide)H2] indicate that the complex dissociates in vivo and is excreted slowly via the liver. The triaminodiamido copper(II) complexes are approximately 2 log units more stable than their diamino analogues. Computer simulation calculations indicate that these complexes are also likely to dissociate in plasma. Measured partition coefficients, however, suggest the possibility of dermal absorption.

Amides↗
PubMed2000

Measurement of brake response time after right anterior cruciate ligament reconstruction.

Recommendations on safe driving after anterior cruciate ligament (ACL) reconstruction have been largely intuitive. This study evaluated 12 male patients who underwent ACL reconstruction with subsequent outpatient rehabilitation and compared them with 10 subjects who had no knee dysfunction. The following clinical measures were assessed every 2 weeks for 10 weeks: brake response time (BRT), 6-meter walk time (6MWT), knee range of motion (ROM), pain (visual analog scale), and joint effusion. Statistical testing was completed using analysis of covariance with repeated measures. The results from treatment group were compared with norms from the AAA Traffic Safety and Engineering Department. BRT showed significant differences over 10 weeks (P =.043) in the study group. There were no significant differences between the study and control group based on condition (ACL reconstruction v control) (P =.586). Pain and effusion were found to have no significant interaction effect on BRT. The treatment group's BRT increased from the 25th percentile (AAA normals) to the 87th percentile after 10 weeks of rehabilitation. Although treatment group BRT was equal to AAA normal population BRT at week 4, the large improvement from week 2 to week 4 meant that learning effects could not be ruled out until week 6. Significant differences were found for 6MWT between week 2 and all other weeks (P <.0001). The results suggest brake reaction time matches control times at 4 to 6 weeks. Thus, BRT might be used to establish return to driving criteria (in part) after ACL reconstruction if other driving impediments do not exist.

Adult↗
PubMed2000

Scattering of sonic booms by anisotropic turbulence in the atmosphere

An earlier paper [J. Acoust. Soc. Am. 98, 3412-3417 (1995)] reported on the comparison of rise times and overpressures of sonic booms calculated with a scattering center model of turbulence to measurements of sonic boom propagation through a well-characterized turbulent layer under moderately turbulent conditions. This detailed simulation used spherically symmetric scatterers to calculate the percentage of occurrence histograms of received overpressures and rise times. In this paper the calculation is extended to include distorted ellipsoidal turbules as scatterers and more accurately incorporates the meteorological data into a determination of the number of scatterers per unit volume. The scattering center calculation overpredicts the shifts in rise times for weak turbulence, and still underpredicts the shift under more turbulent conditions. This indicates that a single-scatter center-based model cannot completely describe sonic boom propagation through atmospheric turbulence.

Journal Article↗
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↗
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↗