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Biomedical subjects

K Kelly

Publications and source records attributed to K Kelly.

At least 199 records · Page 11Linked to original sources
PubMed1990

Tumour cell activity markers in epithelial ovarian cancer: are biochemical and cytometric indices complementary?

Flow cytometry has enabled the objective assessment of cellular morphology and activity, which can also be biochemically evaluated by measuring products of cellular metabolism, such as cyclic 3'5' guanosine monophosphate (cGMP). Using paraffin-embedded formalin-fixed material obtained from the primary operation, an analysis of the correlation between nuclear ploidy and the proliferative index (PI) as quantified by flow cytometry with pre-treatment urinary cGMP was performed in 40 epithelial ovarian cancer (EOC) patients. The majority of the study group had advanced disease (28 FIGO III/IV) and residual disease (31). All but three (stage I) patients received single agent high dose cisplatinum as first-line therapy (100 mg m-2 x 5); in patients with evaluable disease there was a response rate of 64%. Thirty-one patients have died; the median survival of the study population being 27 months. There was a significant association between cGMP and PI. Significantly more aneuploid tumours had elevated PI values (P = 0.02). No variable predicted response. An initial univariate log rank analysis identified stage, the amount of residual disease, cGMP and PI as prognostic factors. Because of the interrelation between these and other factors and because PI did not conform to the proportional hazards model, a multivariate stepwise discriminant analysis was performed using survival at 36 months (the minimum follow-up for surviving patients) as the end-point. On the basis of this analysis, stage and residual disease were the most important prognostic factors, but cyclic GMP continued to have prognostic value even when these other factors were entered into the predictive model. However, the additional information gained has little clinical relevance.

Biomarkers, Tumor↗
PubMed1990

Effects of monocular occlusion on neural and motor response times for two-dimensional stimuli.

Previous studies have shown that there are advantages associated with the simultaneous use of both eyes to view two-dimensional stimuli. To investigate further this binocular advantage, three experiments were conducted using male and female names presented on a video display as stimuli. In the first experiment, simple reaction times (RT's) were found to increase by about 6% as a result of monocular occlusion. In the second experiment, visual evoked response (VER) and P300 implicit times were also found to increase as a result of occlusion. The third experiment confirmed these results and investigated the sensitivity of evoked potential techniques to changes in stimulus complexity. The three experiments demonstrate that monocular occlusion does have a significant effect on processing speed for two-dimensional visual stimuli. The major portion of this effect (62%) is manifest at the level of the visual cortex, and is not perceived by subjects as significantly increasing the mental workload associated with generating responses to these stimuli.

Adult↗
PubMed1990

Adjunct executive appointment for faculty. An innovation in nursing collaboration.

The need for collaboration has never been greater. The healthcare delivery system faces unprecedented challenges arising from prospective payment, competition in the marketplace, higher patient acuity levels, and a shortage of professional nursing staff. The authors discuss a service-education collaboration model based on adjunct executive appointments of faculty members to healthcare organizations. The authors describe the model, a conceptual framework to guide its development, case studies of its implementation, and a summary of the benefits and risks associated with the initial implementation of the model.

Hospitals, Community↗
PubMed1990

Cerebral calcification and learning disabilities following cranial irradiation for medulloblastoma.

Six children who received craniospinal irradiation for medulloblastoma when they were under 10 years of age developed learning disabilities. Four exhibited associated temporal lobe calcification on computerized tomography of the brain. The pathogenetic mechanisms of postirradiation cerebral calcification and learning disabilities in these children are discussed. We present the hypothesis that irradiation-induced vasculopathy results in hypoxia, most pronounced in the hippocampus. Hippocampal damage can manifest radiologically as calcifications and clinically as memory and learning disabilities.

Brain Diseases↗
PubMed1990

Perfluorochemical perfusion during coronary angioplasty in unstable and high-risk patients.

Perfluorochemical perfusion during coronary angioplasty was performed in 38 patients with unstable ischemic syndromes or with high-risk lesions in a single-blind crossover study. Patients received alternate 90-second balloon inflations with and without distal perfusion of oxygenated perfluorochemical (Fluosol, Alpha Therapeutic Corp., Los Angeles, California) at 60 ml/min. Efficacy was assessed by anginal intensity, hemodynamic and electrocardiographic parameters, and left ventricular function determined by two-dimensional echocardiography during balloon inflations. There was a trend toward lower anginal intensity with Fluosol perfusion at 30, 60, and 90 seconds of occlusion. Pulmonary wedge pressure increased significantly with and without Fluosol perfusion, and the magnitude of change was not different. Cardiac output decreased significantly less with Fluosol perfusion than with routine inflation for the total group (-0.8 vs. -1.2 l/min, p less than 0.01) and in the subgroup with left anterior descending coronary artery (LAD) angioplasty (-0.7 vs. -1.5 l/min, p less than 0.001). Left ventricular ejection fraction (EF) by echocardiography declined significantly less with Fluosol perfusion (-4.0 vs. -7.9 EF units, p less than 0.004) than with routine inflation for the total population and declined significantly less with Fluosol in the subgroup with LAD angioplasty (-5.5 vs. -9.7 EF units, p less than 0.008). Regional wall-motion abnormality score increased significantly with routine inflation (from 0.7 +/- 1.4 to 3.5 +/- 3.2, p less than 0.001) and did not change with Fluosol perfusion (from 0.8 +/- 1.3 to 1.3 +/- 1.1, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Cyclosporin A-mediated inhibition of mitogen-induced gene transcription is specific for the mitogenic stimulus and cell type.

We have examined the effect of cyclosporin A (CSA) on the mitogen-induced expression of 11 genes previously cloned from mitogen-activated T lymphocytes. Levels of induced gene expression in the human T cell line Jurkat were determined by mRNA blotting and nuclear run-on assay, after stimulation with one or combinations of the mitogens PMA, PHA, and the ionophore A23187. In the presence of CSA, gene expression induced with PMA alone was not inhibited, whereas PHA-induced increases in gene expression were inhibited by CSA. For one group of genes, including IL-2 and two novel genes with sequences suggestive of lymphokines, A23187 plus PMA-induced gene expression was inhibited by CSA. In contrast, another group of induced genes was unaffected by CSA after A23187 and PMA induction. This finding implies that A23187 and PMA stimulate gene induction by more than one mechanism, and that not all activation signals mediated through calcium fluxes are sensitive to CSA. In addition, 8 of the 11 genes were expressed in the fibroblast cell line Mrc 5 after stimulation with PMA, A23187, or serum; CSA had no effect on genes induced with these agents in Mrc 5 cells in both mRNA blotting and run-on experiments, although 5 of these genes were markedly inhibited by CSA in Jurkat after PMA/PHA induction. These data indicate that separate pathways for induction of identical genes exist, and that the inciting stimulus and cell type are determining factors in the ability of CSA to inhibit gene expression.

Calcimycin↗
PubMed1989

Mitogenic activation of human T cells induces two closely related genes which share structural similarities with a new family of secreted factors.

Previously we have isolated about 60 novel cDNA clones whose corresponding mRNAs are induced by mitogenic activation in human peripheral blood T cells. Here we describe the primary structure and regulation of two such cloned genes, pAT 464 and pAT 744, which may encode new lymphokines/cytokines. Similar to IL-2, both genes require the synergy of agents such as PHA and PMA for optimal expression, and, in addition, the induction of both is sensitive to the immunosuppressive drug cyclosporin A. The two genes can be expressed in T cells, B cells, and the promyelocytic cell line HL60, but they are not expressed in human fibroblasts, suggesting that their expression is restricted to hematopoietic lineages. The predicted peptides encoded by these two clones feature hydrophobic N-terminal leaders characteristic of secreted proteins. The predicted size of both proteins is about 8 kDa upon cleavage of the putative leader peptide. pAT 464 and pAT 744 are very similar to each other and also share some critical amino acid similarity with a newly emerging family of secreted factors including connective tissue activating factor III, platelet factor 4, an IFN-gamma-induced factor, macrophage inflammatory protein, and a factor chemotactic to neutrophils (3-10C, monocyte-derived neutrophil chemotactic factor, neutrophil-activating factor). Some of these factors have been shown to display functions associated with an inflammatory response and/or have mitogenic activities. Collectively, the data presented here suggest that pAT 464 and pAT 744 encode novel lymphokines/cytokines which may play roles during an immune response similar to those enacted by these structurally related factors.

Amino Acid Sequence↗
PubMed1989

Unusual characteristics of Codium fragile chloroplast DNA revealed by physical and gene mapping.

A complete physical map of the Codium fragile chloroplast genome was constructed and the locations of a number of chloroplast genes were determined. Several features of this circular genome are unusual. At 89 kb in size, it is the smallest chloroplast genome known. Unlike most chloroplast genomes it lacks any large repeat elements. The 8 kb spacer region between the 16S and 23S rRNA genes is the largest such spacer characterized to date in chloroplast DNA. This spacer region is also unusual in that it contains the rps12 gene or at least a portion thereof. Three regions polymorphic for size are present in the Codium chloroplast genome. The psbA and psbC genes map closely to one of these regions, another region is in the spacer between the 16S and 23S rRNA genes and the third is very close to or possibly within the 16S rRNA gene. The gene order in the Codium genome bears no marked resemblance to either the "consensus" vascular plant order or to that of any green algal or bryophyte genome.

Chloroplasts↗
PubMed1989

Response of patients in phase II studies of chemotherapy in ovarian cancer: implications for patient treatment and the design of phase II trials.

Results using the same drug in phase II studies of treatment in ovarian cancer vary widely. An analysis of five phase II studies with a total of 93 patients was carried out to determine whether factors other than the efficacy of the drug affect response. The drugs for the phase II studies were chosen on the basis of in vitro activity or previous activity in humans. Univariate analysis showed that several factors were of significance in predicting response. The most significant was interval from the end of previous treatment to entry into a phase II study. Others were the original presenting stage of the patient, the second line treatment given and the best previous response to therapy. In multivariate analysis, however, only two factors were shown to be of importance which were interval and the FIGO stage of the patient. Using these two variables the discriminant analysis predicted 89% of those who did not respond and 75% of those who did, with an overall correct prediction of 85%. The importance of interval is emphasised by the observation that the response rate for those patients who progressed on treatment or who relapsed within 3-6 months of primary therapy had a response rate of less than 10%. Future phase II studies should probably exclude patients in this category, since the chance of their responding is very low.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

The role of metoclopramide in acute and delayed chemotherapy induced emesis: a randomised double blind trial.

High dose metoclopramide is an effective anti-emetic for use with cisplatin containing chemotherapy regimens but can cause extrapyramidal reactions. Lorazepam and dexamethasone are increasingly being used to alleviate chemotherapy induced emesis. This trial has assessed the contribution of high dose metoclopramide to anti-emetic control when given with dexamethasone and lorazepam. Eight-one patients receiving chemotherapy, mainly for gynaecological malignancy, entered a randomised double blind cross-over trial comparing dexamethasone and lorazepam with or without a 24 h metoclopramide infusion. This was followed by oral dexamethasone with or without oral metoclopramide for three further days depending on the initial randomisation. Sixty-one patients were fully evaluable. Fifty-five received cisplatin containing regimens and six non-cisplatin regimens. There was a significant reduction in the number of episodes of vomiting during the first 24 h in patients receiving the metoclopramide combination (P = 0.0001). On first exposure to chemotherapy 45% of patients receiving dexamethasone, lorazepam and high dose metoclopramide had no vomiting while 67% had two episodes or less ('major control'). This compared to 11% total control and 25% major control in those receiving dexamethasone, lorazepam and placebo. The control of nausea in the first 24 h was also improved (P = 0.0001). There was no difference in the degree of nausea or vomiting during the following three weeks between those receiving oral dexamethasone alone and those receiving dexamethasone and metoclopramide. Both groups showed a significant increase in nausea in the three weeks following the second course of treatment when compared to the first (P = 0.0007). Extrapyramidal reactions were recorded in 11.5% of patients receiving metoclopramide. More patients stated a preference for the metoclopramide combination although this was not statistically significant (chi 2(1) = 0.29, P = 0.59). In conclusion the combination of dexamethasone and lorazepam can give major control of emesis in 25% of patients receiving very emetogenic chemotherapy. The addition of metoclopramide increases this to 67% on first exposure to chemotherapy, but at the expense of extrapyramidal reactions in 11.5%.

Adult↗
PubMed1989

Ethylene-associated phase change from juvenile to mature phenotype of daylily (Hemerocallis) in vitro.

Hemerocallis plantlets maintained in vitro for extended periods of time in tightly closed culture vessels frequently show a phenotype, albeit on a miniaturized scale, typical of more mature, field-grown plants. The positive relationship of elevated ethylene in the headspace of such vessels to the phase shift from juvenile to mature form is established. Rigorous restriction in air exchange with the external environment by means of silicone grease seals hastens the phase change and improves uniformity of response. Although some plantlets may take longer to accumulate enough ethylene in sealed jars to undergo change, added ethylene and ethylene-releasing agents promote it. Ethylene adsorbants (e.g. mercuric perchlorate) block the shift of juvenile to mature form. Critical ambient ethylene level for the shift is ca 1 microliter l-1. Levels up to 1000 microliters l-1 do not hasten the response but are not toxic. The phase change is fully reversible when air exchange permits ethylene to drop below 1 microliter l-1. At least 1 microliter l-1 ethylene is required to sustain the mature phenotype. The ethylene synthesis inhibitor aminoethoxyvinylglycine (AVG) prevents the phase change, while the ethylene biosynthesis intermediate 1-aminocyclopropanecarboxylic acid (ACC) improves it. KOH, as a CO2 absorbent, does not prevent the phase change. Histology sections demonstrate subtle changes in the form of shoot tips of plantlets undergoing phase change.

Abscisic Acid↗
PubMed1989

Binding of anti-EMA, AGF 4:48 and the lectin UEA-1 to human ovarian carcinomas: histological and clinical correlations.

The staining reactions of the monoclonal antibodies anti-EMA, AGF 4:48 and the lectin UEA-1 from Ulex europaeus were investigated in formalin-fixed, paraffin-embedded sections of 36 primary ovarian carcinomas. The staining patterns were graded and related to tumour type, differentiation, FIGO stage and patient survival. Both antibodies and UEA-1 showed variations in their staining between and within tumours. The staining of mucinous tumours using anti-EMA was significantly less than in non-mucinous tumours. No other significant associations were found between staining grade and the different variables under study. The variations in staining were not demonstrated to have any prognostic significance.

Adenocarcinoma, Mucinous↗
PubMed1989

Mitogen-induced genes are subject to multiple pathways of regulation in the initial stages of T-cell activation.

The delivery of a mitogenic signal to T cells via any one of several cell surface molecules elicits a variety of intracellular responses, some or all of which regulate subsequent gene expression events. The expression of nine novel mitogen-induced genes in response to various T-cell-activating agents was examined to evaluate the diversity of pathways which regulate such genes. The relative contribution of distinct secondary signals, individually or together, to mitogen-stimulated gene induction and the capability of individual genes to respond to the sometimes divergent signals generated from different cell surface structures is addressed. The activation of T cells with mitogenic monoclonal antibodies directed against the CD2 or CD3 cell surface molecules, or with phytohemagglutinin, induced all nine genes. Thus, stimulation by fully mitogenic agents regardless of cell surface-binding specificity correlated with the expression of all of the genes studied. However, heterogeneous patterns of gene expression, encompassing five regulatory classes, were revealed by the use of phorbol 12-myristate 13-acetate, calcium ionophore, and anti-CD28 monoclonal antibody, agents which mediated only a subset of intracellular events and thus an incomplete mitogenic signal. Interleukin-2 and two novel lymphokines represented one regulatory class that appeared to require unique transcriptional activation signals relative to the other mitogen-induced genes. As demonstrated in the accompanying paper (P. F. Zipfel, S. G. Irving, K. Kelly, and U. Siebenlist, Mol. Cell. Biol. 9:1041-1048, 1989), the immediate transcriptional response of T cells to mitogenic stimulation is quite complex, involving numerous genes beyond those which have been previously described. Furthermore, the discrimination of several regulatory phenotypes among these nine genes suggests that a multiplicity of signaling pathways extends from the cell surface to the level of transcription.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Complexity of the primary genetic response to mitogenic activation of human T cells.

We describe the isolation and characterization of more than 60 novel cDNA clones that constitute part of the immediate genetic response to resting human peripheral blood T cells after mitogen activation. This primary response was highly complex, both in the absolute number of inducible genes and in the diversity of regulation. Although most of the genes expressed in activated T cells were shared with the activation response of normal human fibroblasts, a significant number were more restricted in tissue specificity and thus likely encode or effect the differentiated functions of activated T cells. The activatable genes could be further differentiated on the basis of kinetics of induction, response to cycloheximide, and sensitivity to the immunosuppressive drug cyclosporin A. It is of note that cyclosporin A inhibited the expression of more than 10 inducible genes, which suggests that this drug has a broad genetic mechanism of action.

Cyclosporins↗
PubMed1989

Residual breast carcinoma after biopsy: role of mammography in evaluation.

The records of 21 consecutive patients referred for breast-conservation treatment of early-stage mammary carcinoma contained insufficient histopathologic documentation of adequate resection margins after tumor excision at other hospitals. All patients underwent postbiopsy mammography before reexcision of the tumor bed. In 12 of the 21 cases, there was pathologic evidence of macroscopic or microscopic residual tumor. In seven of the 12 cases, there was no clinical or mammographic evidence to suggest residual carcinoma. The findings indicate that mammography is insufficient to evaluate the completeness of tumor excision in the absence of histopathologic documentation.

Biopsy↗
PubMed1989

Fluoxetine added to non-MAOI antidepressants converts nonresponders to responders: a preliminary report.

Thirty depressed outpatients poorly responsive to various non-MAOI antidepressants had fluoxetine added to their regimens. Retrospective analysis revealed that 26 (86.7%) of the patients improved. Non-MAOI antidepressant treatment was withdrawn for 12 of the 26 responders; of these, 8 relapsed on fluoxetine treatment alone but recovered when treatment with the discontinued non-MAOI agent was restarted.

Adult↗