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S Chandler

Publications and source records attributed to S Chandler.

At least 37 records · Page 2Linked to original sources
PubMed1992

Coupled down-regulation of the RB retinoblastoma and c-myc genes antecedes cell differentiation: possible role of RB as a "status quo" gene.

The ability of the well known morphogen, retinoic acid (RA), as well as 1,25-dihydroxy-vitamin D3 (VD), whose receptor complex binds a DNA consensus sequence related to that of the retinoic acid receptor, to regulate expression of the retinoblastoma (RB) tumor suppressor gene in a context of induced cell differentiation was characterized. HL-60 human promyelocytic leukemia cells were induced to undergo myeloid or monocytic terminal cell differentiation by these agents. To investigate the potential coupling between down-regulation of RB and c-myc oncogene expression with cell differentiation, dose response relationships for the induced down-regulation of RB and c-myc expression were compared with each other and with induced cell differentiation. The total amount of RB protein per cell increased as cells advanced through the cell cycle, but the amount of RB protein relative to the total cell mass remained approximately constant. Treated with RA or VD, an early progressive decrease in cellular content of the RB protein occurred in all cell cycle phases well before any cell cycle modulation or phenotypic differentiation. For a differentiation-defective variant HL-60 cell line, failure to differentiate was preceded by a failure to down-regulate cellular levels of the RB protein. In dose response experiments, progressively increasing RA or VD concentrations caused progressively greater reductions in RB as well as c-myc expression with an increasing fraction of cells terminally differentiating. For both RA and VD, the dose response relationships for reductions in RB and c-myc expression were similar suggesting that their down-regulation may be coupled. These observations are consistent with a model whereby RB expression acts as a cellular brake to sustain a developmentally ordained state of differentiation (i.e., preserve the "status quo"); and the down-regulation of heterogeneously distributed RB protein per cell below a threshold is part of the metabolic cascade culminating in terminal cell differentiation. Thus, RB may have a role in this developmental context.

Calcitriol↗
PubMed1991

Cytomegalovirus testing: antibody determinations and virus cultures with recommendations for use.

Human cytomegalovirus is a ubiquitous virus with the property of becoming latent in the immunocompetent host. It can also cause devastating infections in the immunocompromised patient. Several different assays are available to detect either cytomegalovirus antibodies or cytomegalovirus itself, five of which are used at the University of Wisconsin Hospitals and Clinics and the Wisconsin State Laboratory of Hygiene. The latex agglutination (LA) test is used to detect antibody positivity in transplant donors, transplant recipients, and others. The complement fixation (CF) test is used to detect seroconversion or reactivation of infection in the CMV positive host. The immunofluorescent antibody-IgM (IFA-IgM) test is used to diagnose infection in congenitally or neonatally infected infants. The "routine" CMV culture is the "gold standard" for the detection of the cytomegalovirus in patient secretions. The shell vial assay, a rapid method of detecting virus, is most useful when contemplating therapy for active CMV infection. The advantages and limitations, as well as the timing and appropriateness of each test, are reviewed.

Antibodies, Viral↗
PubMed1991

Regulated expression of the RB "tumor suppressor gene" in normal lymphocyte mitogenesis: elevated expression in transformed leukocytes and role as a "status quo" gene.

Expression of the RB retinoblastoma tumor suppressor gene product is regulated early during the stimulation of normal human peripheral blood lymphocytes, suggesting a regulatory role for the amount of this protein in mitogenesis of normal cells. When normal human peripheral blood lymphocytes were mitogenically stimulated with pokeweed mitogen, bivariate flow cytometric measurements of cellular DNA and RB protein content showed an early decrease in the amount of RB protein per cell, anteceding onset of S phase. A subsequent increase in the amount of RB protein per cell occurred with cell proliferation. Thus the amount of RB protein relative to the total cell mass underwent a biphasic response with mitogenesis. The resulting proliferating cells had a slightly elevated level of RB protein per cell compared to the unstimulated cells. Comparison of other proliferating leukocytes to normal lymphocytes showed that both EBV virally transformed lymphocytes and human promyelocytic leukemia cells (HL-60) had elevated levels of RB protein per cell compared to normal peripheral blood lymphocytes. Mitogenic stimulation or transformation by other means thus is associated with regulation of the amount of RB protein per cell, suggesting a regulatory role for the RB protein in normal cell growth control.

B-Lymphocytes↗
PubMed1991

Bone marrow hypervascularity in patients with myelofibrosis identified by infra-red thermography.

Infra-red thermography was used to assess bone marrow vascularity in six patients with myelofibrosis secondary to myeloproliferative disorders (four primary myelofibrosis and two primary proliferative polycythaemia). The technique was evaluated with conventional static and dynamic radio-isotopic imaging and with immunohistochemical staining of bone marrow biopsies. Infra-red thermography identified increased bone marrow blood flow in patients with established myelofibrosis and correlated with dynamic radio-isotopic studies of blood flow and hypervascularity identified by immunohistochemistry. Increased bone marrow blood flow and vascular proliferation was not confined to the central bone marrow but also extended into the peripheral marrow of the long bones. Endothelial cell proliferation may be an initiating event in the pathogenesis of myelofibrosis but evaluation of bone marrow vascularity and blood flow has hitherto relied on invasive and complicated techniques. This study has identified bone marrow hypervascularity in patients with myelofibrosis and shown infra-red thermography to be a simple non-invasive method of assessing vascularity. This non-invasive technique may be used to study disease progression and response to therapeutic regimens in patients with myelofibrosis and to study bone marrow blood flow in other bone marrow disorders.

Biopsy↗
PubMed1989

Cell cycle-dependent regulation of phosphorylation of the human retinoblastoma gene product.

The human retinoblastoma gene (RB1) encodes a protein (Rb) of 105 kilodaltons that can be phosphorylated. Analysis of Rb metabolism has shown that the protein has a half-life of more than 10 hours and is synthesized at all phases of the cell cycle. Newly synthesized Rb is not extensively phosphorylated (it is "underphosphorylated") in cells in the G0 and G1 phases but is phosphorylated at multiple sites at the G1/S boundary and in S phase. HL-60 cells that were induced to terminally differentiate by various chemicals lost their ability to phosphorylate newly synthesized Rb at multiple sites when cell growth was arrested. These findings suggest that underphosphorylated Rb may restrict cell proliferation.

Cell Cycle↗
PubMed1989

Percutaneous transluminal coronary angioplasty in patients with reduced left ventricular ejection fraction: effects on myocardial perfusion and left ventricular response to exercise.

Many patients with coronary artery disease treated by percutaneous transluminal coronary angioplasty (PTCA) have a history of previous myocardial injury resulting in a reduced left ventricular ejection fraction (EF). The effects of successful PTCA on myocardial perfusion and left ventricular function in these patients were compared to treatment in patients with normal left ventricular EF. There were 21 patients with a normal EF (mean EF 59 +/- 2%) (Group I) and 15 patients with reduced EF (mean EF 43 +/- 1%) (Group II). Before PTCA a similar degree of reversible myocardial ischemia was present on thallium scintigraphy. At peak exercise left ventricular EF in the Group I patients decreased by 4 +/- 1% compared to 8 +/- 1% in Group II. At one month following successful PTCA there was resolution of reversible myocardial ischemia in both groups. No changes in EF at rest were observed. At the same level of exercise as before PTCA the mean EF was 5 +/- 1% higher than the pretreatment value in Group I and 10 +/- 1% higher in Group II. Thus in this study reversible myocardial ischemia was associated with severe compromise in the left ventricular response to exercise which was substantially improved by PTCA.

Angioplasty, Balloon↗
PubMed1987

Myocardial salvage following elective angioplasty for total coronary occlusion.

A 65-year-old man with unstable angina had a critical left anterior descending coronary artery stenosis which progressed to total occlusion, without evidence of acute myocardial infarction. Thallium imaging revealed defects in the distribution of the left anterior descending coronary artery on exercise and redistribution, 4 h later. 99mTc radionuclide angiography showed a fall in left ventricular ejection fraction on exercise, and contrast cineangiography showed an extensive area of akinesia. Percutaneous transluminal coronary angioplasty was successful without any complications. Repeat radionuclide studies demonstrated improvement of both myocardial perfusion and function. Angiography at 1 year showed normal left ventricular contraction and no evidence of recurrent stenosis. The patient is free of angina, on no medication 2 years after angioplasty. This case illustrates the feasibility of myocardial salvage by elective coronary angioplasty in patients with unstable angina total coronary occlusion.

Aged↗
PubMed1986

Iodinated cholylglycyltyrosine: a new agent for hepatobiliary imaging.

The characteristics of radiolabelled cholylglycyltyrosine (CGT), a recently synthesised bile acid, were studied. 125I-CGT-Na was found to have a short plasma half-life of 1.6 +/- 0.4 min in rats and 3.1 +/- 0.7 min in dogs. Biliary clearance studies showed the cumulative biliary output of the tracer over 20 min in rats to be 95.7% of the total dose administered, with a mean biliary transit time (50% retention time) of 4.0 +/- 0.1 min, i.e. similar to the biliary kinetics of taurocholate. 131I-CGT-Na proved to be satisfactory for hepatobiliary imaging in rats and dogs at doses of 35 microCi (1.3 MBq) in rats and 90 microCi (3.3 MBq) in dogs. Satisfactory hepatic images were also obtained in rats that had high bilirubin levels produced by obstruction or the recycling of bile. These results show that CGT has better pharmacokinetics than currently used hepatobiliary imaging agents, and that this new compound may be useful in scintigraphy even in the presence of jaundice.

Animals↗
PubMed1985

Size of spleen rather than amount of platelet sequestration may determine long term responses to splenectomy in adult idiopathic thrombocytopenic purpura.

Fourteen adults with idiopathic thrombocytopenic purpura suffered a relapse after treatment with steroids, vinca alkaloids, or intravenous gammaglobulin. Splenic sequestration of platelets labelled with 111In-oxine was assessed, and the patients then underwent splenectomy. During follow up of four to 47 months (mean 20.7) none of the patients required further treatment, including three of 14 who showed partial relapses. Splenic sequestration patterns did not predict relapses, but an unexpected finding was that patients who relapsed had significantly smaller spleens. It is concluded that splenectomy is beneficial in most adult patients with idiopathic thrombocytopenic purpura and that radiological techniques to measure the size of the spleen may be useful in predicting which patients may relapse.

Adolescent↗
PubMed1983

Improved tumour localisation using indium-111 labelled antibodies.

Immunoglobulin G (IgG) antibodies to carcinoembryonic antigen (CEA) were labelled with radioactive indium (111In) or iodine (131I) and a comparison made of their value in locating CEA producing tumours. Eleven patients given 111In-anti-CEA had 31 tumours as judged by a combination of all techniques. Of these, 28 were detected by 111In-anti-CEA and 26 by conventional clinical techniques. Five of the patients also received 131I-anti-CEA. These patients had 15 tumour areas. Thirteen were detected by 111In and eight by 131I. 111In also produced a better signal to noise ratio in the scans and thereby showed lesions with greater certainty. In addition, the 111In isotope continued to accumulate in the tumour areas for considerably longer than 131I. Absorbed doses (whole body) were similar for both isotopes. The results show that antibody scanning is greatly improved by using 111In as the radiolabel in place of 131I and should allow the detection of smaller or deeper lesions.

Carcinoembryonic Antigen↗
PubMed1983

Detection of thyroid tumours using radio-labelled anti-thyroglobulin.

IgG antibody to human thyroglobulin was labelled with 131Iodine (131I) and used to locate deposits of thyroid follicular and papillary tumours with a gamma camera. Of twelve patients studied a total of 40 tumour 'areas' were detected by a variety of clinical and radiological techniques. Sixteen of these were detected using conventional 131I uptake scans whereas 34 were positive on the antibody scans. The difficulty of assessing diffuse pulmonary lesions (3 areas) and the possibility that free 131I from labelled antibody may have contributed to the antibody scan results in six areas left 31 definite areas for scan comparison. Twenty seven (87%) areas were positive on the antibody scan, nine (29%) were positive on conventional 131I scans whilst 24 (77%) areas were detected by a combination of clinical and other radiological criteria. Five areas were positive on the antibody scan alone but there was evidence, albeit indefinite, that these areas contained tumour. Four of the 31 areas were not detected by the antibody scans. The results indicate that anti-thyroglobulin scanning is more sensitive than conventional 131I-iodide scans and may contribute to the staging and management of thyroid cancer.

Adult↗