Biomedical subjects
Publications and source records attributed to M Kelly.
'Upenamide (1) represents a new class of macrocyclic marine alkaloid possessing both spirooxaquinolizidinone and hemiaminal ring systems. It was isolated from the Indonesian sponge Echinochalina sp. The gross structure of 1 was elucidated by spectroscopic methods and accurate mass measurements. A suggestion is made as to its biogenetic origin.
From the dichloromethane/2-propanol (1:1) extract of the Indonesian marine sponge Strepsichordaia aliena, twelve new 20, 24-bishomoscalarane sesterterpenes, honulactones A-L (1-12) were isolated. Molecular structures were secured by spectroscopic methods, accurate mass measurements, and X-ray analysis. Honulactones A (1), B (2), C (3), and D (4) exhibit cytotoxycity against P-388, A-549, HT-29, and MEL-28 (IC(50) 1 microg/mL).
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.
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.
The major limitations of Moloney murine leukemia virus (MoMLV)-based vectors for human stem cell applications, particularly those requiring bone marrow (BM) stem cells, include their requirement for mitosis and retroviral receptor expression. New vectors based upon lentiviruses such as HIV-1 exhibit properties that may circumvent these problems. We report that novel third-generation, self-inactivating lentiviral vectors, expressing enhanced green fluorescent protein (EGFP) and pseudotyped with vesicular stomatitis virus G glycoprotein (VSV-G), can efficiently transduce primitive human repopulating cells derived from human BM and cord blood (CB) tested by the SCID-repopulating cell (SRC) assay. Highly purified CD34+ CD38- CB or BM cells were efficiently transduced (4-69%) and stably expressed in EGFP for 40 days in culture following infection for only 24 h without fibronectin, polybrene, or cytokines. Nonobese diabetic/severe combined immune-deficient (NOD/SCID) mice transplanted with transduced cells from either CB or BM donors were well engrafted, demonstrating maintenance of SRC during the infection procedure. Serially obtained femoral BM samples indicated that the proportion of EGFP+ cells within both myeloid and lymphoid lineages was maintained or even increased over time, averaging 42.3 +/- 6.6% for BM donors and 23.3 +/- 7.2% for CB at 12 weeks. Thus, the third-generation lentivectors readily transduce human CB and BM stem cells, under minimal conditions of ex vivo culture, where MoMLV-based vectors are ineffective. Since CB is inappropriate for most therapeutic applications, the efficient maintenance and transduction of BM-derived SRC during the short infection procedure are notable advantages of lentivectors.
BACKGROUND: Pituitary adenomas are considered benign tumors and metastases are seen when the tumor shows malignant transformation. CASE DESCRIPTION: We present a case of a benign pituitary adenoma with multiple dural metastasis without malignant transformation throughout its course. At all times, the pituitary adenoma remained benign as seen by a lack of nuclear pleomorphism, nuclear atypia, vascular invasion, and absence of immunohistochemical staining for p53 protein. CONCLUSION: This is a rare example of dural metastasis from a benign pituitary adenoma. The authors believe this is the fourth reported case of this type in the literature.
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.
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.
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.
We present the cases of two women with chronic ectopic pregnancies who presented with acute tubal rupture and hemoperitoneum despite negative beta-human chorionic gonadotropin (beta hCG) pregnancy tests. The appropriate screening use of beta hCG assays to ascertain pregnancy status, the mechanisms by which ectopic pregnancy may be seen with negative beta hCG tests, and the limitations of various assays are discussed. One patient, not initially believed to be pregnant, underwent computed tomography (CT) scan. Experience with use of CT scan in ectopic pregnancy diagnosis is limited; our case illustrates some of the possible CT scan findings. These cases illustrate the potential for ectopic pregnancy to rupture with low, if not undetectable beta hCG hormone levels, and consequently why it is not recommended to rely on quantitative beta hCG levels to guide the decision to proceed with ultrasound imaging.
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.
From the methanolic extract of the Red Sea sponge Callyspongia sp. six new polyacetylenic compounds, aikupikanynes A-F, together with octahydrosiphonochalyne, were isolated and identified. Their structures, which comprise four hydrocarbons, two alcohols, and one unprecedented alpha-hydroxy carboxylic acid, were determined by extensive 1D and 2D NMR studies and mass spectral determinations.
Investigation of the lipophilic extract of the sponge Strepsichordaia aliena revealed six new 20,24-bishomoscalarane sesterterpenes, honu'enone (1), phyllofolactones H-K (3-6), and phyllofenone C (7). Structure elucidation of these compounds was secured by spectroscopic methods, 1D and 2D NMR, and accurate mass measurements.
Two new sesquiterpenes, pelorol (1) and 5-epi-smenospongine (2), and seven known ones (3-9) were isolated from the sponge Petrosaspongia metachromia, collected from Yap, Federated States of Micronesia. Their structures were determined from spectral data. Pelorol (1) possesses a new carbon skeleton.
This study considers the interrelationships among coping, conflictual social interactions, and social support, as well as their combined associations with positive and negative mood. Research has shown that each of these variables affects adjustment to stressful circumstances. Few studies, however, examine this full set of variables simultaneously. One hundred forty HIV-infected persons completed a questionnaire containing measures of coping, social support, conflictual social interactions, and positive and negative mood. Factor analyses showed that perceived social support and conflictual social interactions formed separate factors and were not strongly related. Compared to perceived social support, social conflict was more strongly related to coping behaviors, especially to social isolation, anger, and wishful thinking. Conflictual social interactions were more strongly related to negative mood than was perceived social support. Coping by withdrawing socially was significantly related to less positive and greater negative mood. The findings point to the importance of simultaneously considering coping, supportive relationships, and conflictual relationships in studies of adjustment to chronic illness. In particular, a dynamic may occur in which conflictual social interactions and social isolation aggravate each other and result in escalating psychological distress.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
BACKGROUND: Health care organizations face pressures from patients to improve the quality of care and clinical outcomes, as well as pressures from managed care to do so more efficiently. Coordination, the management of task interdependencies, is one way that health care organizations have attempted to meet these conflicting demands. OBJECTIVES: The objectives of this study were to introduce the concept of relational coordination and to determine its impact on the quality of care, postoperative pain and functioning, and the length of stay for patients undergoing an elective surgical procedure. Relational coordination comprises frequent, timely, accurate communication, as well as problem-solving, shared goals, shared knowledge, and mutual respect among health care providers. RESEARCH DESIGN: Relational coordination was measured by a cross-sectional questionnaire of health care providers. Quality of care was measured by a cross-sectional postoperative questionnaire of total hip and knee arthroplasty patients. On the same questionnaire, postoperative pain and functioning were measured by the WOMAC osteoarthritis instrument. Length of stay was measured from individual patient hospital records. SUBJECTS: The subjects for this study were 338 care providers and 878 patients who completed questionnaires from 9 hospitals in Boston, MA, New York, NY, and Dallas, TX, between July and December 1997. MEASURES: Quality of care, postoperative pain and functioning, and length of acute hospital stay. RESULTS: Relational coordination varied significantly between sites, ranging from 3.86 to 4.22 (P <0.001). Quality of care was significantly improved by relational coordination (P <0.001) and each of its dimensions. Postoperative pain was significantly reduced by relational coordination (P = 0.041), whereas postoperative functioning was significantly improved by several dimensions of relational coordination, including the frequency of communication (P = 0.044), the strength of shared goals (P = 0.035), and the degree of mutual respect (P = 0.030) among care providers. Length of stay was significantly shortened (53.77%, P <0.001) by relational coordination and each of its dimensions. CONCLUSIONS: Relational coordination across health care providers is associated with improved quality of care, reduced postoperative pain, and decreased lengths of hospital stay for patients undergoing total joint arthroplasty. These findings support the design of formal practices to strengthen communication and relationships among key caregivers on surgical units.