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Biomedical subjects

M Sullivan

Publications and source records attributed to M Sullivan.

At least 19 recordsLinked to original sources
PubMed1992

Thoracic spinal calcinosis circumscripta causing cord compression in two German shepherd dog littermates.

Two young German shepherd dog littermates had progressive, painless, hindlimb ataxia. In both dogs plain radiography of the vertebral column revealed a solitary mineralised lesion on the dorsal laminae between the dorsal spines of the second and third thoracic vertebrae, and myelography with iopamidol demonstrated cord compression at the level of the lesions. The first dog died 18 hours after the myelography. A dorsal laminectomy performed in the second dog resulted in neurological improvement. A histopathological examination confirmed that both lesions were calcinosis circumscripta. The cause of the death of the first dog was meningitis.

Animals↗
PubMed1992

Adipogenesis in a myeloid supporting bone marrow stromal cell line.

The bone marrow stroma contains pre-adipocyte cells which are part of the hemopoietic microenvironment. Cloned stromal cell lines differ both in their ability to support myeloid and lymphoid development and in their ability to undergo adipocyte differentiation in vitro. These processes have been examined in the +/+2.4 murine stromal cell line and compared to other stromal and pre-adipocyte cell lines. In long-term cultures, the +/+2.4 stromal cells support myeloid cell growth, consistent with their expression of macrophage-colony stimulating factor mRNA. However, despite the presence of mRNA for the lymphoid supportive cytokines interleukins 6 and 7, +/+2.4 cells failed to support stromal cell dependent B lineage lymphoid cells in vitro, suggesting that these stromal cells exhibit only a myelopoietic support function. The +/+2.4 cells differentiate into adipocytes spontaneously when cultured in 10% fetal bovine serum. The process of adipogenesis can be accelerated by a number of agonists based on morphologic and gene marker criteria. Following induction with hydrocortisone, methylisobutylxanthine, indomethacin, and insulin in combination, a time dependent increase in the steady state mRNA and enzyme activity levels of the following adipocyte specific genes was observed: adipocyte P2, adipsin, CAAT/enhancer binding protein, and lipoprotein lipase. In contrast, adipogenesis was accompanied by a slight decrease in the signal intensity of the macrophage-colony stimulating factor mRNA level, similar to that which has been reported in other bone marrow stromal cell lines. These data demonstrate that although the lympho-hematopoietic support function of pre-adipocyte bone marrow stromal cell lines is heterogeneous, they share a common mechanism of adipogenesis.

Adipose Tissue↗
PubMed1992

Intracellular modifications induced by poliovirus reduce the requirement for structural motifs in the 5' noncoding region of the genome involved in internal initiation of protein synthesis.

A series of genetic deletions based partly on two RNA secondary structure models (M. A. Skinner, V. R. Racaniello, G. Dunn, J. Cooper, P. D. Minor, and J. W. Almond, J. Mol. Biol. 207:379-392, 1989; E. V. Pilipenko, V. M. Blinov, L. I. Romanova, A. N. Sinyakov, S. V. Maslova, and V. I. Agol, Virology 168:201-209, 1989) was made in the cDNA encoding the 5' noncoding region (5' NCR) of the poliovirus genome in order to study the sequences that direct the internal entry of ribosomes. The modified cDNAs were placed between two open reading frames in a single transcriptional unit and used to transfect cells in culture. Internal entry of ribosomes was detected by measuring translation from the second open reading frame in the bicistronic mRNA. When assayed alone, a large proportion of the poliovirus 5' NCR superstructure including several well-defined stem-loops was required for ribosome entry and efficient translation. However, in cells cotransfected with a complete infectious poliovirus cDNA, the requirement for the stem-loops in this large superstructure was reduced. The results suggest that virus infection modifies the cellular translational machinery, so that shortened forms of the 5' NCR are sufficient for cap-independent translation, and that the internal entry of ribosomes occurs by two distinct modes during the virus replication cycle.

DNA Mutational Analysis↗
PubMed1992

A poliovirus replicon containing the chloramphenicol acetyltransferase gene can be used to study the replication and encapsidation of poliovirus RNA.

A poliovirus replicon, FLC/REP, which incorporates the reporter gene chloramphenicol acetyltransferase (CAT) in place of the region encoding the capsid proteins VP4, VP2, and part of VP3 in the genome of poliovirus type 3, has been constructed. Transfection of cells indicates that the FLC/REP replicon replicates efficiently and that active CAT enzyme is produced as a CAT-VP3 fusion protein. The level of CAT activity in transfected cells broadly reflects the level of FLC/REP RNA. A series of mutations in the 5' noncoding region of poliovirus type 3 were introduced into FLC/REP, and their effects were monitored by a simple CAT assay. These experiments helped to define further the stem-loop structures in the 5' noncoding region which are essential for RNA replication. The CAT-containing poliovirus replicon could also be packaged into poliovirus capsids provided by helper virus and was stable as a subpopulation of virus particles over at least four passages. The location of the CAT gene in FLC/REP excluded the presence of an encapsidation signal in the region of the poliovirus genome comprising nucleotides 756 to 1805.

Amino Acid Sequence↗
PubMed1992

Inadequate adrenergic response to disopyramide-induced hypoglycemia.

OBJECTIVE: To report a case of disopyramide-induced hypoglycemia and to discuss the observed inadequate adrenergic response in this patient. Risk factors, possible etiologies, and preventive measures are also discussed. DATA SOURCES: References from case reports and review articles as identified by MEDLINE. DATA SYNTHESIS: A wide variety of drugs has been implicated as causing hypoglycemia. The mechanism for drug-induced hypoglycemia is known for the majority of these agents. Case reports of disopyramide-induced hypoglycemia have been reported in the literature, but the mechanism of action is unclear. We report a case of disopyramide-induced hypoglycemia in which counter-regulatory hormones, serum insulin, and C-peptide concentrations were obtained. From these data, it appears that disopyramide-induced hypoglycemia results from endogenous insulin secretion, with concomitant inadequate counterregulatory response. CONCLUSIONS: Although a rare occurrence, disopyramide-induced hypoglycemia is potentially life-threatening. Patients at risk for this reaction need to be identified prior to the institution of disopyramide therapy. Patients at risk for hypoglycemia should be monitored while on disopyramide and disopyramide blood concentrations should be maintained at the lower end of the therapeutic range, or alternative agents should be considered.

Aged↗
PubMed1992

Cardiac isoenzymes following heart transplantation.

Creatine phosphokinase (CPK) isoenzymes are commonly obtained after heart transplantation (HT) to assess myocardial injury of the donor heart. This investigation retrospectively evaluated the utility of this practice. Fifty-six recipients of orthotopic heart transplants had at least two daily CPK-MB studies following HT. All patients were followed up for at least one year (or until death). Nineteen patients had entirely negative CPK-MB determinations (NEG). Eighteen patients had a single positive CPK-MB determination, and were considered to be equivocal (EQUIV). Nineteen patients had more than one daily positive CPK-MB determination (POS). To evaluate the influence of positive CPK-MB determinations on the outcome of HT, we compared the results in the NEG and POS groups. There was no difference in the donor organ ischemic times between the two groups. The duration of follow-up for the two groups was also similar (1,192 days vs 1,020 days). The NEG and POS groups had no significant difference in: 1 year survival (84 percent vs 74 percent); freedom from treated rejection episodes in 3 months (39 percent vs 42 percent); and freedom from coronary artery disease (CAD) at 3 years (83 percent vs 86 percent). Additionally, the ejection fractions of the donor hearts were similar at 1 year post-transplant for the 2 groups (64 percent vs 59 percent). We conclude that myocardial injury, as reflected by post-transplant CPK-MB levels, does not predict one-year mortality, predisposition to rejection, predisposition to coronary artery disease, or ultimate graft dysfunction. In an effort to perform HT more economically, we no longer obtain CPK-MB levels following HT.

Clinical Enzyme Tests↗
PubMed1992

Quality of life during chemotherapy for small cell lung cancer. II. A longitudinal study of the EORTC Core Quality of Life Questionnaire and comparison with the Sickness Impact Profile.

Sixty-two patients with small cell lung cancer, 36-80 years of age, who were receiving chemotherapy during a maximum of one year, were consecutively included in a study of quality of life during treatment. An interim version (C-36) of the EORTC Core Quality of Life Questionnaire (QLQ) was applied for quality of life assessment prior to treatment and every third month during the treatment period. The assessments were related to clinical variables (performance status and tumour response), and compared with results from assessment with the Sickness Impact Profile (SIP). The QLQ was sensitive to differences in clinical status and responded to clinical change over time. In general, the pattern of correlations with SIP lends support to the construct validity of the QLQ. However, some questions arose from the comparison with SIP: QLQ emotional functioning did not change in concordance with SIP, and assessment of social functioning was not optimal prior to treatment. The questionnaire was well accepted by the patients. The EORTC QLQ C-36 constitutes a promising step in the development of a feasible standard instrument for quality of life assessment in cancer clinical trials.

Aged↗
PubMed1991

Transforming growth factor-beta modulates eicosanoid metabolism in osteogenic osteosarcoma cells.

The metabolites of cycloxyegenase and lipoxygenase pathways are known to play an important role in the bone metabolism involving osteoclast and osteoblast interaction, bone resorption and morphogenesis. The recently discovered growth factor TGF-beta is abundant in bone and some of its intracellular and extracellular effects depend on de novo synthesis of eicosanoids. However, the effect of TGF-beta on the synthesis and the release of eicosanoid by bone cells is essentially unknown. In the present study we have identified the main eicosanoid metabolites produced by osteogenic osteosarcoma cell-line SAOS1 and investigated how production and release of these is affected by TGF-beta. We found that the leukotriene C4 is the main metabolite produced by these cells and that TGF-beta induces concentration-dependent, quantitative and qualitative alterations in eicosanoid production and release by human osteogenic osteosarcoma cells SAOS1.

Arachidonic Acid↗
PubMed1991

Effects of detomidine on equine oesophageal function as studied by contrast radiography.

The effects of sedation with detomidine on oesophageal function were assessed by contrast radiography in 10 healthy adult thoroughbred horses. Barium swallows were monitored by means of image intensification, first without sedation and then after the intravenous administration of detomidine at doses of 10 and 20 micrograms/kg bodyweight. The transit time of contrast agent to the oesophageal hiatus was recorded and each swallow was scored for markers of oesophageal dysfunction. Analysis of the data indicated that there were highly significant dose dependent increases in the transit time, the retention of barium within the longitudinal mucosal folds, and retrograde peristalsis and pooling of contrast agent within the oesophagus at both the thoracic inlet and caudal to the base of the heart. The degree of gastrooesophageal reflux was not affected at either dosage. These changes in oesophageal function were similar to those recorded from cases of grass sickness and indicate that care should be taken in the interpretation of studies of swallowing in animals that have been given detomidine before a radiographic examination.

Animals↗
PubMed1991

Finding meaning after the fall: injury narratives from elderly hip fracture patients.

Hip fractures occur frequently among the elderly, often with severe medical, psychological and social repercussions. This research takes a new look at hip fracture rehabilitation, focusing on meanings and post-fracture prognostic indicators. An innovative methodological approach to narrative analysis is employed which combines ethnographic and epidemiologic techniques. Analyses of injury narratives from 80 elderly subjects interviewed soon after initial hospitalization are presented, focusing on three categories of meaning: explanatory models, sense of disability, and futurity. Insights from these narratives, as well as from questionnaires and observations, shed light on the experience of hip fracture for the elderly. In addition, aspects of the initial narratives are considered in relation to ambulation outcomes at 3 and 6 months. Those individuals who perceive their problem in a more external or mechanical fashion (caused by the environment) show greater improvement in ambulation at 3 and 6 months relative to those who show no evidence of this thinking or who perceive it as an internal or organic problem (in terms of disease or illness). Greater improvement in ambulation at 3 and 6 months is also noted for subjects whose perception of disability was consistent with more autonomy, independence, and a sense of connection with the world around them. The present study demonstrates the potential utility of narrative analysis as a data reduction approach. It also suggests the possibility of new psychosocial prognostic factors for hip fracture rehabilitation.

Accidental Falls↗
PubMed1991

Cardiac transplantation in patients with preexisting malignancies.

A history of preexisting malignancy has been considered a contraindication to cardiac transplantation. The reasons for this prejudice include concerns about potentially deficient intrinsic immunomodulation and fear of cancer recurrence (or development of second cancers) because of therapeutic immunosuppression. In the past four years at the Northern Indiana Heart Institute seven patients with preexisting malignancies underwent cardiac transplantation. Their two-year survival rate was 100%, which is comparable to a rate of 81% in non-malignancy patients. After an average 31 months of follow-up (range = 6-56 months), only one patient has had a recurrent tumor (basal cell carcinoma). Statistical comparison of immunosuppression dosages, incidences of rejection, and incidences of infections between patients with preexisting malignancy and those without preexisting malignancy was performed. We found that the only significant difference was an increased number of infections in preexisting malignancy patients. Additionally, we found no difference in the incidence of posttransplant coronary artery disease in the preexisting malignancy group when compared with those patients without preexisting malignancies. This study demonstrates that patients who have been successfully treated for malignancies have no greater incidence of rejection than those patients without preexisting malignancy. Furthermore, preexisting malignancy patients require no significant modulation of immunosuppression. Although preexisting malignancy patients have a higher incidence of infections than patients without preexisting malignancy, their two-year survival is not worse than the patients without preexisting malignancy.

Adult↗
PubMed1991

D1 dopamine receptors can interact with both stimulatory and inhibitory guanine nucleotide binding proteins.

Pretreatment of striatal membranes with N-ethylmaleimide in the presence of a D1-specific agonist inactivated endogenous guanine nucleotide binding proteins (G proteins), but not D1 dopamine receptors, resulting in a loss of high-affinity agonist binding sites. Such D1 receptors were solubilized, mixed with exogenous G proteins from cells not containing D1 receptors, and reconstituted into phospholipid vesicles. These reconstituted receptors were able to couple to the exogenous G proteins, and the proportion of agonist high-affinity sites of the receptor (40-57%) was similar to levels obtained with naive receptors coupling to endogenous G proteins (40%) upon solubilization and reconstitution. These hybrid high-affinity sites were fully modulated by guanine nucleotides. Pretreatment of cells with pertussis toxin prior to extraction of G proteins resulted in a 50% decrease in the proportion of high-affinity sites; these sites remained sensitive to guanine nucleotides. When D1 receptors were reconstituted with extracts of cyc- cells, which lack stimulatory G proteins, the proportion of high-affinity sites was reduced to 31% of the total. Pertussis toxin treatment of the cyc- cells completely abolished the formation of high-affinity sites. These results demonstrate that D1-dopaminergic receptors are able to couple to not only stimulatory G proteins (Gs), but also to inhibitory G proteins (Gi).

Animals↗
PubMed1991

Polyomavirus large T mutants affected in retinoblastoma protein binding are defective in immortalization.

To clarify the relationship between the various activities of the polyomavirus large T antigen and the contribution of this oncogene to neoplastic transformation, we constructed a series of mutants with small deletions or single-amino-acid substitutions in two separate regions of the protein. These sequences were targeted because they showed considerable similarity to conserved regions 1 and 2 of adenovirus E1A which are thought to be binding sites for the retinoblastoma gene product (pRB). The pRB-binding properties of the large T mutants were assessed with an in vitro coimmunoprecipitation assay. pRB binding was readily detected with wild-type large T, but coprecipitation was completely abolished by as little as a single amino acid substitution (Asp-141----Glu or Glu-146----Asp) in region 2 of the polyomavirus large T antigen. Mutants defective in pRB binding were unable to immortalize primary rat embryo fibroblasts, suggesting that association with pRB is an important component of immortalization mediated by polyomavirus large T. The mutations in region 1 affected pRB binding only marginally, yet some of them severely impaired immortalization, indicating that pRB binding may be essential but not sufficient for immortalization.

Amino Acid Sequence↗
PubMed1991

Investigating the proxy effect and the saliency principle in household based postal questionnaires.

STUDY OBJECTIVE: The aim was to investigate two possible sources of bias inherent in using a household based postal questionnaire, the "proxy effect", inaccurate reporting about characteristics of others, and the "saliency principle", reporting of only the most salient features. This is of importance in surveys concerned with screening the population to identify individuals with certain characteristics, and so possibly relying on one member of the household to reply on behalf of all others. DESIGN AND SETTING: A two stage survey of disablement in the population was undertaken. A first phase postal questionnaire was sent to 25,168 households in Calderdale, West Yorkshire, England, to ascertain the prevalence of physical disability and of troubles with the joints. The second phase comprised in depth interviews with a sample of individuals identified in the first phase as being disabled. RESPONDENTS: A total of 21,889 postal questionnaires were returned (87%) representing households containing 42,826 people aged 16 years and over. A disproportionately stratified random sample of 950 respondents reporting disability was taken in the second phase. Of these 891 were still available, and 838 (94%) were interviewed. MEASUREMENTS AND MAIN RESULTS: The postal questionnaire found that almost 29% of those who lived "alone" (without another adult) reported some level of disability, compared to only 10% of those who lived with others. The difference remained significant after standardisation. This apparent underreporting or "proxy effect" was present for reporting about disability overall, but not for severe disability (dependence on help of others), which suggests the operation of the "saliency principle". Reporting on joint troubles appeared to be affected by the proxy effect both for any joint problems, and when more than five joints were affected. Analysis of a small set of postal questionnaires from respondents who reported joint problems only at interview and where we could identify who had completed the postal questionnaire supports the hypothesis of a proxy effect; two thirds of the original postal questionnaires had been completed by a proxy. The results were further complicated by an interaction between reporting of disability and joint troubles: the greater the level of disability, the less likely the reporting of joint troubles. CONCLUSIONS: The findings have general implications for studies involving postal household screening questionnaires, and raises additional concerns about those that are multitopic in content. In surveys of symptoms and minor disability, a proxy effect is likely to be operative. This effect is not apparent for obvious and long standing problems such as dependence on others for help. However the interaction between the reporting of disability and joint symptoms carries important implications for the development of multitopic postal screening questionnaires.

Adolescent↗