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K Kelly

Publications and source records attributed to K Kelly.

At least 217 records · Page 12Linked to original sources
PubMed1989

A comparison between the findings of a routine school dental inspection and epidemiological data from the same five year old children.

This study examines the need for standardised examiners to collect data on 5-year-old children. Data collected at routine school inspections by non-standardised dental officers are compared with data collected by a standardised epidemiologist using the criteria recommended by the British Association for the Study of Community Dentistry. Both sets of data were gathered from one sample of 638 children. Comparisons between results are made for the total sample, for the three health districts concerned and at individual school level. For the total sample there was a mean difference of 0.05 dmft between the dental officers' data and the epidemiologist's data but in one district identical results were achieved. Comparisons between districts showed that both data sets identified the same statistically significant differences; for example, both showed one district to have significantly higher levels of caries than the other two. At individual school level regression analysis gave a very high level of agreement (r = +0.94) between the two data sets. If mean values of dmft continue to be reported as indicators of child dental health, data collected at routine dental inspections on large samples may be adequate for this age group.

Child, Preschool↗
PubMed1988

Interaction of thrombin-stimulated platelets with vitronectin (S-protein of complement) substrate: inhibition by a monoclonal antibody to glycoprotein IIb-IIIa complex.

Platelets adhere to vitronectin substrate following activation with physiological concentrations of thrombin. Adhesion of activated platelets to vitronectin substrate is dependent upon the presence of divalent cations, the amount of vitronectin, and the duration of adhesion assay. The adhesion of platelets is inhibited by synthetic peptides containing the sequence of Arg-Gly-Asp. In addition, monoclonal antibodies to glycoprotein IIb-IIIa complex inhibit the adhesion of activated platelets to vitronectin substrate in a dose-dependent manner. These studies suggest that the glycoprotein IIb-IIIa complex on activated platelets may interact with vitronectin substrate through the Arg-Gly-Asp mechanism. Since vitronectin is present in the subendothelial matrix, it might be involved in platelet-vessel wall interactions.

Antibodies, Monoclonal↗
PubMed1988

Failure of second-look laparotomy to influence survival in epithelial ovarian cancer.

The survival benefit of second-look laparotomy after completion of primary chemotherapy in patients with epithelial ovarian cancer has been assessed in a prospective randomised trial of 166 patients. Patients were randomised into three groups. All were initially treated with cisplatin (100 mg/m2 x 5) after primary laparotomy. Group A (n = 53) was scheduled to have a second-look laparotomy, followed by cyclical oral chlorambucil. Group B (n = 56) was scheduled to have a second-look laparotomy, followed by total abdominal and pelvic irradiation, and group C (n = 57) received oral chlorambucil as for group A but had no second-look operation. With a median follow up of 46 months (range 21-64), no differences in survival were noted between the three groups. The median survival for group A was 21 months (95% CI 11-31 months), for group B 15 months (11-19), and for group C 17 months (8-26). Thus second-look laparotomy after completion of first-line single-agent cisplatin chemotherapy did not confer any survival benefit on patients with epithelial ovarian cancer.

Actuarial Analysis↗
PubMed1988

Mitogenic activation of normal T cells leads to increased initiation of transcription in the c-myc locus.

Early following mitogenic activation, normal human T cells express elevated levels of steady-state mRNAs encoding the nuclear-localized protooncogenes, c-fos, c-myc, and c-myb. Although the mechanisms responsible for increases in these specific mRNAs are not known, recent evidence suggests that up-regulation of c-myc could result from the release of a nascent chain elongation block. Run-on transcription analyses of c-myc show here that increased initiation and not modulation of elongation efficiency is largely responsible for elevated c-myc mRNA levels in activated T cells. Transcriptional stimulation of c-myc commences from a chromatin state that appears poised for activation. As determined by DNase I hypersensitive site analyses, the chromatin structure of c-myc in resting T cells resembles that of other cell types expressing high levels of c-myc, and furthermore, no changes in hypersensitive sites can be correlated with mitogenic stimulation of c-myc transcription. Because mitogen-induced up-regulation and terminal differentiation-associated down-regulation of c-myc are mechanistically different, it appears that c-myc is subject to a variety of distinct transcriptional controls. In addition to c-myc, c-fos and c-myb are shown to be induced via a transcriptional mechanism in T cells.

Cells, Cultured↗
PubMed1988

Evidence that the catalytic differences of two structurally homologous forms of cytochrome P-450 relate to their heme environment.

Cytochromes P-450 PB3a and PB3b, which appear to be equivalent to forms b and e described by Ryan et al. [Ryan, D.E., Thomas, P.E., & Levin, W. (1982) Arch. Biochem. Biophys. 216, 272-288], have been shown to share 97% sequence homology [Suwa, Y., Mizukami, Y., Sogawa, K., & Fujii-Kuriyama, Y. (1985) J. Biol. Chem. 260, 7980-7984] yet exhibit an intriguing difference in enzymatic activity. Studies to establish the basis for this difference, including a development of the technique of surface-enhanced resonance Raman spectroscopy (SERRS), are reported. Studies on substrate binding, metabolism, and redox properties, as well as SERRS, indicate a significant difference in the heme environment of these two proteins. No significant difference in the interaction of the two proteins with P-450 reductase could be established. However, this interaction appeared sensitive to changes in ionic strength, suggesting ionic interactions are important in the functional coupling of these electron-transport components. A marked variation in the ratio of PB3a to PB3b activity in the metabolism of different substrates, which included a series of structurally similar resorufin analogues, provided further evidence that reductase coupling was not a critical factor. Therefore, the few amino acid differences observed between these proteins indicate sites that may be important in influencing the heme environment of these cytochrome P-450's.

Animals↗
PubMed1988

Complex partial seizures. Correlation of clinical and metabolic features.

We compared metabolic patterns on 18F-2-deoxyglucose positron emission tomography (PET) with closed circuit television and simultaneous electroencephalographic ictal recordings of complex partial seizures in 48 patients. Closed circuit television and electroencephalographic data and PET scans were scored by "blinded" raters. Of the 48 patients, 26 had unilateral temporal; three, frontal; ten, ipsilateral frontotemporal; one, frontoparietal; and five, temporoparietal hypometabolism; and three had widespread hypometabolism affecting frontal, temporal, and parietal lobes. patients with frontal hypometabolism alone had shorter ictal and postictal durations, but involvement of multiple regions was associated with prolonged seizures. Auras were more likely to be present in patients with temporal hypometabolism alone, but an initial motionless stare did not distinguish this group. However, other metabolic patterns did not predict specific ictal clinical features. Vocalizations (formed or unformed) were not more closely associated with frontal involvement. When hypometabolism is multilobar, it may be difficult to use PET to distinguish between complex partial seizures of frontal and temporal origin.

Brain↗
PubMed1988

CD4+ CD8+ cells are rare among in vitro activated mouse or human T lymphocytes.

The predominant cell type in the thymus expresses both of the function-associated T cell surface markers, CD4 and CD8, but CD4+ CD8+ cells are rare or absent outside the thymus. Double expression has therefore been assumed to be an indication of immaturity. However, recent reports have suggested that CD4+ CD8+ cells can appear in cultures of activated mature cells. We have therefore activated human peripheral blood lymphocytes and mouse spleen cells, lymph node cells, and cortisone-resistant thymocytes using a number of different stimulation regimes, and we have analyzed them at various times for CD4 and CD8 expression. In all cases, upon analysis of cultured cells by flow cytometry, CD4+ CD8+ cells were rare. A combination of microscopic analysis, cell sorting followed by microscopic analysis, and careful staining controls demonstrated that even when flow cytometry showed some CD4+ CD8+ cells, most of these were artifacts in the form of doublets or clumps of single positive cells or dead cells. Taking this into account, CD4+ CD8+ cells made up less than 1% in the mouse and less than 3% in the human T cell cultures at any time periods. We therefore found no evidence for the generation of large numbers of CD4+ CD8+ cells in cultures of mouse or human T cells.

Adult↗
PubMed1988

Drug response patterns as a basis of nosology for the mood-incongruent psychoses (the schizophrenias).

Interaction of therapeutic drugs with a series of different biopathological substrates of psychosis might be expected to generate a series of different response patterns. Herein the authors suggest that multi-modal response patterns following lithium and neuroleptic treatment of psychotic patients may aid in resolving the heterogeneity of psychotic disorders and lead to a new nosology of the psychoses.

Haloperidol↗
PubMed1988

A genetic linkage study of a family with Norrie's disease.

A family having one member with Norrie's disease, X-linked retinal dysplasia associated with hearing loss and mental retardation, was studied using DNA markers. The DNA markers were used to try and confirm the diagnosis of Norrie's disease by detecting a deletion of the X chromosome. Linkage analysis using the polymorphic DNA markers was performed and this allowed more accurate determination of the carrier status of two sisters of the affected boy than by empiric risk calculation. The advantage of multiple polymorphic DNA markers for linkage analysis is illustrated.

Chromosome Mapping↗
PubMed1988

The surface phenotype of activated T lymphocytes.

The surface phenotype of T cells reflects both their relative maturity and their activation state. To determine the pattern of surface markers characteristic of activated T cells, purified mature T cells were stimulated in vitro for periods of 0.5-5 days with Concanavalin-A (Con-A) or phorbol myristic acetate (PMA) and ionomycin, fluorescein-labelled with monoclonal antibodies, then analysed by flow cytometry. The level of expression of the function-associated antigens CD4 (L3T4) and CD8 (Ly-2) decreased transiently early after activation with PMA/ionomycin, but not after stimulation with Con-A. Both stimuli caused a small drop in the level of CD3 and the T cell antigen receptor (TCR). At no time was CD3, CD4 or CD8 completely lost from the surface. Following activation Pgp-1, the interleukin-2 (IL-2) receptor (as detected by the monoclonal antibody 7D4) and the peanut agglutinin (PNA) receptor were gained by a proportion of cells, MEL-14 was lost by a proportion of cells, and no change was observed in the expression of heat stable antigen. Thy-1 or Ly-1. From the present data no evidence has been found for the generation of the 'immature', CD4- CD8- phenotype found in the thymus by activation of mature T cells. During T cell development, however, changes in expression of Pgp-1, MEL-14, the IL-2 receptor and the PNA receptor may be associated with activation, rather than differentiation per se.

Animals↗
PubMed1988

Interim report of a randomized trial comparing Zoladex 3.6 mg depot with diethylstilbestrol 3 mg/day in advanced prostate cancer. The West Midlands Urology Research Group.

A study comparing Zoladex 3.6 mg depot with diethylstilbestrol (DES) 3 mg/day was initiated in August 1985. One hundred ninety-three patients with histologically confirmed prostate cancer T3/4 or M1 have been randomized up to 31 March 1987: 95 to Zoladex, 98 to DES. No patient had received prior systemic therapy. There is no bias in the treatment groups in terms of baseline characteristics. Median follow-up is 11 months, and the response rate at 12 months from randomization (CR + PR) for Zoladex is 70 +/- 9.4% and 50 +/- 10.1% for DES. Median time to best response is 6 months for Zoladex and 12 months for DES (using the Kaplan-Meier life table method). Subjective responses are 56 +/- 10.2% for Zoladex and 44 +/- 10% for DES. Five increases in bone pain were found after the first Zoladex treatment, as well as one increased ureteric obstruction. None required treatment withdrawal. Seventeen patients on DES were withdrawn due to adverse reaction (chi 2 = 4.33, 1df, p less than 0.05). Overall survival at 31 March 1987 is 84% for the Zoladex group and 78% for the DES group. This study has shown that Zoladex is superior to DES in achieving early tumor response in advanced prostate cancer, without causing serious complications warranting withdrawal of treatment.

Buserelin↗
PubMed1988

Developmental status and reconstitution potential of subpopulations of murine thymocytes.

In this chapter we have summarized our view of the subsets of murine CD4- CD8- thymocytes which can be identified with a range of monoclonal antibodies. We have shown the division rate and turnover time of the main subsets and have listed what we know of the TcR gene rearrangement, and expression at the RNA and protein levels. We have been unable to completely segregate gamma delta-TcR-expressing cells from alpha beta-TcR-expressing cells by any of the markers we have used, although the proportions of the two receptor forms vary widely in the different subsets. Experiments involving intrathymic transfer of the CD4- CD8- subsets are described, which indicate that all the TcR- subsets of the CD4- CD8- thymocytes display some precursor activity and which suggest a progression of at least five stages through the TcR- subpopulations of CD4- CD8- cells. The earliest precursor is a Thy 1 low, HSA low, Pgp-1 high cell which has unrearranged C beta and is non-dividing and which closely resembles the bone marrow prothymocyte. The later precursors are Thy 1 high, HSA high, Pgp-1 low, have rearranged C beta and are rapidly dividing. We tentatively conclude that none of the TcR+ CD4- CD8- cells are precursors of the major thymocyte subsets or of typical peripheral T cells, and we have found no evidence so far of separate precursors for the different mature subsets of thymocytes or peripheral T cells.

Animals↗
PubMed1988

Two distinct mechanisms of transcriptional control operate on c-myc during differentiation of HL60 cells.

We examined the mechanisms that control the downregulation of the c-myc mRNA during differentiation of HL60 cells. On treatment with dimethyl sulfoxide, HL60 cells downmodulated their steady-state c-myc message levels, ceased to proliferate, and underwent terminal differentiation. In nuclear run-on assays in which distinct segments of the c-myc gene were used as probes, an increased blocking to elongation of nascent c-myc transcripts was shown during the early phase of differentiation. During a later phase, however, a loss of transcriptional initiation was observed. This loss of promoter activity correlated well with dramatic changes in the chromatin structure of the c-myc gene, as determined by DNase I-hypersensitive site analysis. In particular, two hypersensitive sites near the two major c-myc promoters disappeared at the time that promotion abated. The newly described, later-acting negative transcriptional control of c-myc also correlated temporally with the inability to reverse the downregulation of the c-myc message quickly on withdrawal of the differentiating agent. Therefore, a terminal step during differentiation may be linked to the later-acting mode of transcriptional regulation of c-myc. The evidence presented in this report has implications for tumorigenesis in Burkitt lymphomas, in which the germ line, nontranslocated c-myc allele is transcriptionally silent.

Cell Differentiation↗
PubMed1987

Surface enhanced resonance Raman scattering as a probe of the spin state of structurally related cytochromes P-450 from rat liver.

Surface enhanced resonance Raman scattering (SERRS) was observed from structurally related drug-induced rat liver cytochromes P-450 adsorbed on a silver colloid. Careful control of pH and the sequence of addition of components to the so1 is required to prevent protein denaturation at the surface due to conversion to P-450's biologically inactive form P-420 or haem loss. A low-spin P-450 (PB3a), a mixed low- and high-spin P-450 (PB3b) and a predominantly high-spin P-450 (MC1a) were investigated. Spectra recorded in the 1300-1700 cm-1 frequency region, containing the oxidation state marker v4 at 1375 cm-1 (Fe3+) and spin state markers v10 (1625 cm-1, high-spin; 1633 cm-1, low-spin) and v19 (1575 cm-1, high-spin; 1585 cm-1, low-spin) were used to differentiate between the spin states of the various forms of cytochrome P-450. As well as the established spin state marker bands, the intensity of a band at 1400 cm-1 appeared to depend on the high-spin content. Thus, with this method SERRS from silver colloids can be used to determine spin states of related cytochromes P-450 in dilute solution (10(-8)M) and may be of value in studies of protein-substrate interactions.

Animals↗
PubMed1987

AIDS and ethics. An overview.

AIDS has generated a host of ethical questions that are urgent, poignant, and sometimes unprecedented. These questions fall into several familiar categories of ethical problems, including civil liberties vs. public health, distribution of scarce resources, "truth telling," confidentiality, and discrimination, among others. Established ethical principles apply in each of these areas, but certain features of this epidemic require new considerations. Factors such as our current uncertainty about the natural history of infection with HIV, the lack of evidence for transmission through casual contact, the social status of the groups at high risk, the unavailability of any definitive treatment, the tendency of AIDS to affect the central nervous system, and the availability of psychiatric evidence about the effects of hearing the diagnosis should affect the calculation of competing values. In general, there is little ethical justification at this time except in specific and limited situations for infringing on individual civil rights, for permitting discrimination against AIDS patients or those at risk, or for violating confidentiality.

Acquired Immunodeficiency Syndrome↗