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Biomedical subjects

K Ryan

Publications and source records attributed to K Ryan.

At least 37 records · Page 2Linked to original sources
PubMed1996

A randomized, double-blind comparison of single-dose and divided multiple-dose dolasetron for cisplatin-induced emesis.

PURPOSE: Intravenous dolasetron has been shown to be an effective antiemetic agent in patients receiving high-dose cisplatin-containing chemotherapy. Previous studies have suggested that 1.8 mg/kg is an optimal dose for achieving control of emesis and nausea. The objective of this study was to compare the efficacy and safety of a single intravenous (IV) dose of dolasetron with an equal divided multiple dose. METHODS: In this randomized, double-blind, parallel-group, multicenter study, the efficacy and safety of a single 1.8-mg/kg dose of dolasetron given 30 min prior to high-dose cisplatin ( > or = 80 mg/m2) chemotherapy was compared with the same total amount of dolasetron administered in three separate doses (0.6 mg/kg each) over a 12-h interval commencing 30 min prior to beginning chemotherapy and ending 11.5 h later. Antiemetic efficacy, safety, and tolerability were compared in 55 patients with various malignancies during the 24 h following the initiation of chemotherapy. The number of emetic episodes was the primary efficacy parameter. RESULTS: A single IV dose of dolasetron was generally more effective than a multiple-dose regimen in all measures of efficacy. There was a larger proportion of complete responders in the single-dose group compared with the multiple-dose group (48% vs 23%), although this difference did not reach statistical significance. Compared with the multiple-dose group, patients who received a single dose of dolasetron had a significantly (P = 0.034) longer median time to the first emetic episode (10.1 h vs > 24 h, respectively). Overall, 53% of patients had either a complete response or a major response to dolasetron, and only 40% of the total patient population received escape antiemetic medication in the 24 h after cisplatin administration. Except for headache, adverse events were similar with both regimens and were generally of mild or moderate intensity; no serious adverse events occurred. Neither dolasetron treatment regimen was associated with any clinically important events, trends in laboratory variables, or differences in safety profile. CONCLUSIONS: single-dose dolasetron was well tolerated and effectively controlled emesis and nausea in patients who received highly emetogenic, high-dose cisplatin chemotherapy. The greater antiemetic efficacy of a single prophylactic dose of dolasetron offers both convenience and potential cost savings, compared with a multiple-dose schedule of administration.

Aged↗
PubMed1996

An indelible lineage marker for Xenopus using a mutated green fluorescent protein.

We describe the use of a DNA construct (named GFP.RN3) encoding green fluorescent protein as a lineage marker for Xenopus embryos. This offers the following advantages over other lineage markers so far used in Xenopus. When injected as synthetic mRNA, its protein emits intense fluorescence in living embryos. It is non-toxic, and the fluorescence does not bleach when viewed under 480 nm light. It is surprisingly stable, being strongly visible up to the feeding tadpole stage (5 days), and in some tissues for several weeks after mRNA injection. We also describe a construct that encodes a blue fluorescent protein. We exemplify the use of this GFP.RN3 construct for marking the lineage of individual blastomeres at the 32- to 64-cell stage, and as a marker for single transplanted blastula cells. Both procedures have revealed that the descendants of one embryonic cell can contribute single muscle cells to nearly all segmental myotomes rather than predominantly to any one myotome. An independent aim of our work has been to follow the fate of cells in which an early regulatory gene has been temporarily overexpressed. For this purpose, we co-injected GFP.RN3 mRNA and mRNA for the early Xenopus gene Eomes, and found that a high concentration of Eomes results in ectopic muscle gene activation in only the injected cells. This marker may therefore be of general value in providing long term identification of those cells in which an early gene with ephemeral expression has been overexpressed.

Animals↗
PubMed1996

Mitigating engulfment: recovering from a first episode of psychosis.

1. Schizophrenia, and the challenge of coping with the ongoing stigma of mental illness, profoundly affects an individual's self-concept. 2. Individuals in the early phases of schizophrenia are at risk of becoming engulfed by their illness, such that all aspects of self become defined by the illness. 3. A group intervention enabled individuals to construct a positive self-concept through interacting with others, exploring the meaning of illness, developing an acceptable understanding of the illness, and developing diverse coping strategies.

Adaptation, Psychological↗
PubMed1995

Enhanced expression of an insulin growth factor-like binding protein (mac25) in senescent human mammary epithelial cells and induced expression with retinoic acid.

mac25, the subject of this report, was selected by the differential display of mRNA method in a search for genes overexpressed in senescent human mammary epithelial cells. mac25 had previously been cloned as a discrete gene, preferentially expressed in normal, leptomeningial cells compared with meningioma tumors. mac25 is another member of the insulin growth factor-binding protein (IGFBP) family. Insulin-like growth factors are potent mitogens for mammary epithelial cells, and the IGFBPs have been shown to modulate this mitogenic activity. We report here that mac25, unlike most IGFBPs, is down-regulated at the transcription level in mammary carcinoma cell lines, suggesting a tumor-suppressor role. The gene was mapped to chromosome 4q12. We found that mac25 accumulates in senescent cells and is up-regulated in normal, growing mammary epithelial cells by all-trans-retinoic acid or the synthetic retinoid fenretinide. These findings suggest that mac25 may be a downstream effector of retinoid chemoprevention in breast epithelial cells and that its tumor-suppressive role may involve a senescence pathway.

Amino Acid Sequence↗
PubMed1995

Predicting diabetic control from competence, adherence, adjustment, and psychopathology.

OBJECTIVE: To determine what psychological and behavioral factors were most predictive of diabetic control. METHOD: Seventy-nine youths with diabetes were assessed cross-sectionally, using youths' reports of self-esteem, anxiety, and attitudes about diabetes, and parents' reports of competence and psychopathology (from the Child Behavior Checklist) and diabetic adherence as independent variables. Glycosylated hemoglobin A1c was the dependent variable, reflecting diabetic control. After the effects of several background variables were partialed out, a principal-components analysis grouped the substantive variables into three larger components. RESULTS: Among the background variables, duration of illness and family size significantly predicted diabetic control. Among substantive components, Competence/Adherence (including Total Competence, dietary compliance, and frequency of blood glucose checks) was highly predictive of diabetic control, primarily due to the effect of Total Competence. Adjustment (including self-esteem, anxiety levels, and attitudes about diabetes) and Psychopathology were less predictive. A model was constructed showing the relationships between these predictive components and diabetic control. CONCLUSIONS: In this generally well-adjusted sample, that Total Competence, more than other measures, predicted diabetic control suggests it could be used by clinicians to anticipate diabetic youths at risk.

Adolescent↗
PubMed1995

Victims of violence in Fiji.

OBJECTIVE: The aim of the paper is to examine the statistics for violence performed by self or others in Fiji during the period 1969-1989 in the following sub-classifications: (1) fatal vs non-fatal; (2) Fijian vs Indian; and (3) male vs female. METHOD: Crude rates per 100,000 were determined and the data sets were statistically examined. RESULTS: (1) Violence by self, which includes suicide and non-fatal injury by self, has significantly increased; (2) Indian violence by self has increased in both males and females; (3) suicide is 4 times more common than homicide, whereas non-fatal injury by others is 4 times more common than non-fatal injury by self; (4) non-fatal injury by self is 8 times more common than suicide, whereas non-fatal injury by others is over 100 times more common than homicide; (5) Indian violence by self is 6 times more common than Fijian violence by self, whereas Fijians experience violence by others 2.5 times more commonly than Indians; (6) female violence by self is 1.5 times more common than male violence by self, whereas male violence by others is 3 times more common than female violence by others; (7) the rates of suicide and homicide are low by international standards; and (8) Fijian violence by self is particularly low, but consistent with the low suicide rate of the indigenous populations in surrounding geographical regions. CONCLUSION: Our findings suggest that racial differences in violence are likely to be due to cultural factors.

Cause of Death↗
PubMed1994

Factor C*, the specific initiation component of the mouse RNA polymerase I holoenzyme, is inactivated early in the transcription process.

Factor C* is the component of the RNA polymerase I holoenzyme (factor C) that allows specific transcriptional initiation on a factor D (SL1)- and UBF-activated rRNA gene promoter. The in vitro transcriptional capacity of a preincubated rDNA promoter complex becomes exhausted very rapidly upon initiation of transcription. This is due to the rapid depletion of C* activity. In contrast, C* activity is not unstable in the absence of transcription, even in the presence of nucleoside triphosphates (NTPs). By using 3'dNTPs to specifically halt elongation, C* is seen to remain active through transcription complex assembly, initiation, and the first approximately 37 nucleotides of elongation, but it is inactivated before synthesis proceeds beyond approximately 40 nucleotides. When elongation is halted before this critical distance, the C* remains active and on that template complex, greatly extending the kinetics of transcription and generating manyfold more transcripts than would have been synthesized if elongation had proceeded past the critical distance where C* is inactivated. In complementary in vivo analysis under conditions where C* activity is not replenished, C* activity becomes depleted from cells, but this also occurs only when there is ongoing rDNA transcription. Thus, both in vitro and in vivo, the specific initiation-conferring component of the RNA polymerase I holoenzyme is used stoichiometrically in the transcription process.

Animals↗
PubMed1994

Isolation of virulence genes directing GPI synthesis by functional complementation of Leishmania.

Recent advances in molecular genetics of Leishmania parasites prompted us to develop methods of functional genetic complementation in Leishmania and apply them to the isolation of genes involved in the biosynthesis of the virulence determinant LPG, an abundant GPI-anchored polysaccharide. LPG1, the gene product identified by complementation of our R2D2 LPG- mutant, may be a glycosyltransferase responsible for the addition of galactofuranose to the nascent chain. As galactofuranose is not found in mammalian cells, inhibition of the addition of this sugar could be exploited for chemotherapy. Overall, the success of the functional complementation approach opens the way to the identification of a variety of genes involved in pathogenesis and parasitism.

Animals↗
PubMed1994

Down-regulation of retinoic acid receptor beta in mammary carcinoma cell lines and its up-regulation in senescing normal mammary epithelial cells.

Retinoids are important cellular, dietary factors that regulate differentiation and cellular growth. They serve as ligands for specific nuclear receptors, the retinoic acid receptors (RARs). Ligand-activated receptors regulate gene transcription through target retinoic acid-responsive elements (RAREs) found in promoter regions. We have investigated the expression of retinoic acid receptor genes (alpha, beta, gamma) and retinoid X receptor beta in normal, senescing, and tumorigenic human mammary epithelial cells. We find that most tumor cells show a loss of RAR-beta expression, but that RAR-alpha and -gamma as well as retinoid X receptor beta are variably expressed in both normal and tumor cells. RAR-beta gene expression is induced both by retinoic acid and by fenretinide in normal cells, but tumor cells fail to respond to either. In contrast, RAR-beta expression increases with serial passage in senescing cells. Paradoxically, both normal and tumor cells can trans-activate an exogenous beta-RARE, as demonstrated by reporter gene assays. Oligonucleotide mobility shift assays with the beta-RARE show a single discrete complex in normal cells, whereas tumor cells exhibit a heterogeneous set of larger complexes, which indicates that tumor cells utilize a different array of factors within the beta-RARE. Reporter gene assays with extended promoter regions indicate the presence of negative regulatory elements and/or factor binding sites that reside between -1500 and the RARE located at -59, and that the promoter is down-regulated in MCF-7 tumor cells. Our findings reveal a dichotomy: RAR-beta transcription is down-regulated in tumor cells compared with normal human mammary epithelial cells, and up-regulated in senescence.

Base Sequence↗
PubMed1993

Arg15-Lys17-Arg18 turkey ovomucoid third domain inhibits human furin.

Turkey ovomucoid third domain with Leu18 in its reactive site is a potent inhibitor of many serine proteinases: subtilisins, chymotrypsins, and elastases. Previous studies showed that an L18K mutation made it a moderately strong inhibitor of trypsin, while an L18E mutation made it a strong inhibitor of Glu-specific Streptomyces griseus proteinase (GluSGP). For human furin substrates the consensus optimal sequence is RXKR decreases. Therefore the A15R, T17K, and L18R mutations were made in turkey ovomucoid third domain. The mutant inhibits human furin with a Ka of 1.1 x 10(7) M-1. As human furin catalyzes an obligatory step in human immunodeficiency virus proliferation, this inhibitor, along with the others already available, deserves further study.

Amino Acid Sequence↗
PubMed1993

Cardiopulmonary resuscitation skills in non consultant hospital doctors--the Irish experience.

We assessed the Cardiopulmonary Resuscitation (CPR) skills in 30 Non Consultant Hospital Doctors (N.C.H.D.'s) chosen randomly from a total of 110 on the staff of a university associated teaching hospital. The candidates filled out a questionnaire and were asked to perform initial assessment and CPR on a mannikin for two minutes. None of the candidates followed the recognised airway, breathing and circulation ABC sequence and only one provided effective CPR. We suggest there is a need for encouragement for doctors to undergo CPR training with subsequent certification and ongoing refresher courses during their career.

Attitude of Health Personnel↗