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Biomedical subjects

E Henderson

Publications and source records attributed to E Henderson.

At least 19 recordsLinked to original sources
PubMed1992

Hodgkin disease survivors at increased risk for problems in psychosocial adaptation. The Cancer and Leukemia Group B.

BACKGROUND: The long-term psychosocial adaptations of 273 survivors of advanced Hodgkin disease were assessed to determine the nature and extent of problems experienced and to identify those at high risk for maladaptation. METHODS: Hodgkin disease survivors were identified who initially had been treated in clinical trials within the Cancer and Leukemia Group B from 1966 to 1986, were currently disease free, and had completed treatment for a minimum of 1 year. All survivors had advanced Hodgkin disease (with disease diagnosed at a mean age of 28 years). Survivors were at a mean age of 37 years at the time of interview (6.3 years after treatment completion), and 60% were male. Survivors were interviewed over the telephone 7-10 days after questionnaires were mailed to them concerning their psychological, social, vocational, and sexual functioning. RESULTS: Psychological distress was found to be elevated by one standard deviation (SD) above that of healthy subjects on the Brief Symptom Inventory, and 22% met the criterion suggested for a psychiatric diagnosis. In addition, the following problems were reported by survivors to be a consequence of having had Hodgkin disease: denial of life (31%) and health (22%) insurance, sexual problems (37%), conditioned nausea in response to reminders of chemotherapy (39%), and a negative socioeconomic effect (36%). Survivors found to be at high risk for maladaptation were: men earning less than $15,000 per year or who were currently unemployed; unmarried individuals; those with serious illnesses since treatment completion; and those who were less educated. CONCLUSIONS: These findings suggest that including a routine assessment of these factors would help to target survivors in need of additional evaluation and treatment.

Adaptation, Psychological↗
PubMed1992

Actin filament dynamics in living glial cells imaged by atomic force microscopy.

Observation of filamentous actin (F-actin) in living cells is currently limited to the resolution of the light microscope. Higher resolution procedures require sample fixation and preclude dynamic studies. The atomic force microscope (AFM) can image and manipulate samples at very high, sometimes atomic resolution by scanning a fine tip over the surface of interest and detecting physical interactions between the tip and sample. This study demonstrates that F-actin can be readily resolved in living cells with the AFM and that the dynamic properties of F-actin are easily observed.

Actin Cytoskeleton↗
PubMed1992

Pregnancy outcome in survivors of advanced Hodgkin disease.

BACKGROUND: Pregnancy outcome was reported by 139 survivors of advanced Hodgkin disease treated on nine protocols of Cancer and Leukemia Group B from 1966 to 1986. METHODS: These patients provided data on 302 singleton pregnancies of a duration of at least 20 weeks that occurred before, during, or after treatment for Hodgkin disease (252, 26, and 24 pregnancies, respectively). RESULTS: There were 4 perinatal deaths, as compared with 5.7 expected. Cancer subsequently developed in 2 offspring (expected, 1.2). However, 22 newborn infants had low a birth weight, exceeding the expected number of 13.7 (relative risk 1.6; 95% confidence interval, 1.0-2.4). The excess number of low weight births occurred primarily during the period of Hodgkin disease diagnosis and treatment but is based on small numbers. CONCLUSION: No increase in adverse outcome occurred in pregnancies that antedated the development of Hodgkin disease.

Adult↗
PubMed1992

Imaging and nanodissection of individual supercoiled plasmids by atomic force microscopy.

The atomic force microscope (AFM) was used to image supercoiled plasmid DNA deposited on a mica surface in either a hydrated or desiccated state. Hydrated plasmid was precisely cut by the scanning tip at a location determined by the instrument operator. Small pieces of DNA (100-150 nm in length) were excised and deposited adjacent to the dissected plasmid, demonstrating that it is possible to remove and manipulate genomic DNA fragments, unresolvable by light microscopy, from defined chromosomal locations by AFM.

DNA, Superhelical↗
PubMed1992

Formation of novel hairpin structures by telomeric C-strand oligonucleotides.

Telomeres are specialized structures at the ends of chromosomes that are required for long term chromosome stability and replication of the chromosomal terminus. Telomeric DNA consists of simple repetitive sequences with one strand G-rich relative to the other, C-rich, strand. Evolutionary conservation of this feature of telomeric repeat sequences suggests that they have specific structural characteristics involved in telomere function. Absorbance thermal denaturation, chemical modification and non-denaturing gel electrophoretic analyses showed that telomeric C-strand oligonucleotides form stable non-Watson-Crick hairpin structures containing C.C+ base pairs. Formation of such hairpins may facilitate previously reported G-strand exclusive interactions.

Animals↗
PubMed1992

Dehydroepiandrosterone (DHEA) and synthetic DHEA analogs are modest inhibitors of HIV-1 IIIB replication.

Down-regulation of Epstein-Barr virus (EBV) induced transformation of human lymphocytes in vitro by dehydroepiandrosterone (DHEA), a naturally occurring human steroid secreted by the adrenal gland has been demonstrated. This article reports on the effects of DHEA and its novel synthetic analogs 16 alpha-fluoro-5-androsten-17-one (8354) and 3 beta-hydroxy-16 alpha-fluoro-5 alpha-androstan-17-one (OH8356) on human immunodeficiency virus (HIV-1) replication. Treatment with DHEA, 8354, or OH8356 resulted in a modest down-regulation of HIV-1 replication in phytohemagglutinin-stimulated peripheral blood lymphocytes as measured by syncytia formation, release of p24 antigen, and accumulation of reverse transcriptase activity. DHEA and 8354 also reduced syncytia formation in HIV-1-infected SupT1 lymphoblasts. DHEA and synthetic analogs of DHEA, which have been shown previously to have antiproliferative effects, now are shown to reduce HIV-1 replication. DHEA or synthetic analogs of DHEA could provide an alternative and/or adjuvant for HIV-1 infection.

Androstenes↗
PubMed1992

The use of an exponential protocol for bicycle and treadmill exercise testing in patients with chronic cardiac failure.

We have studied a standardized exercise protocol suitable for use with a treadmill or bicycle (STEEP protocol) and compared it with a modified Bruce treadmill protocol in a group of patients with chronic cardiac failure. The STEEP protocol has been previously validated in normal subjects. Exercise time (6.79 +/- 2.42 vs 5.34 +/- 1.95 min, P < 0.05) and peak VO2 (16.66 +/- 4.09 vs 15.01 +/- 3.72 ml.min-1.kg-1, P < 0.05) were greater with the STEEP treadmill compared with the bicycle protocol, but VO2 was very similar at equal exercise stages in both modalities. Heart rate and respiratory exchange ratio tended to be greater during bicycle exercise at equal stages. Exercise time was greater with the modified Bruce protocol (9.00 +/- 3.02 min, P < 0.05) than with either STEEP protocol, but peak VO2 (17.13 +/- 4.52 ml.min-1.kg-1) was similar to that obtained with the STEEP treadmill test. We conclude that the STEEP protocol may be used to test patients with chronic cardiac failure, and that exercise times relate well in both treadmill and bicycle. The protocol should prove useful in studies involving a wide range of exercise capacities or both bicycle and treadmill exercise.

Aged↗
PubMed1992

Urinary collagen crosslinks reflect the radiographic severity of knee osteoarthritis.

The collagen crosslinks deoxypyridinoline and pyridinoline are indices of mature collagen breakdown and reflect increased bone turnover. Urinary levels were found to be significantly raised in a group of 59 women with knee OA compared to 110 female controls from the general population. Levels of the crosslinks correlated significantly with X-ray grade of all subjects including women from the general population with mild, often asymptomatic, disease. These correlations were not diminished after adjustment for age and weight.

Aged↗
PubMed1992

T lymphocyte adhesion to fibronectin (FN): a possible mechanism for T cell accumulation in the rheumatoid joint.

The accumulation of T cells within the joint is responsible for the perpetuation of synovitis. This process is partly regulated by selective binding to endothelium. However, adhesion to extra-cellular matrix proteins, like FN, may also be important. FN binding is mediated by certain members of the VLA (beta 1 integrin) family of proteins. To investigate the role of Tc-FN interactions in synovitis the binding of synovial fluid (SF) and peripheral blood (PB) T cells to FN-coated wells, and the expression of cell surface VLA molecules on these cells by double label immunofluorescence, were studied. SF T cells bound better to FN than PB T cells. VLA alpha 4 and VLA beta 1 but not VLA alpha 5 were up-regulated on SF compared with PB T cells. Anti-VLA alpha 4, VLA beta 1 and VLA alpha 5 MoAbs inhibited the binding of SF T cells to FN. The increased binding of SF T cells to FN could have been related to activation and/or to their predominantly memory phenotype. Purified resting memory or naive T cells bound poorly to FN. In contrast, compared with SF T cells, concanavalin A-activated T cells showed a very similar level of binding to FN, comparable expression of VLA molecules and the same pattern of inhibition of binding to FN by MoAbs. Thus, VLA molecules may play an important role in the retention of T cells in the joint and since T cells can be activated via VLA-FN interactions, this mechanism may perpetuate chronic inflammation.

Arthritis, Rheumatoid↗
PubMed1992

Atomic force microscopy of conventional and unconventional nucleic acid structures.

Images of conventional (Watson-Crick base paired) and unconventional (G4 RNA) nucleic acid structures have been obtained by atomic force microscopy. The images are reproducibly generated from samples deposited on freshly cleaved mica. Periodic substructural features are evident in fibres observed in both cases. In the case of G4 RNA, tip-induced formation of large fibres is observed.

DNA↗
PubMed1992

Increased circulating atrial natriuretic factor concentrations in patients with chronic heart failure after inhibition of neutral endopeptidase: effects on diastolic function.

OBJECTIVE: +/- Candoxatrilat was used to raise atrial natriuretic factor (ANF) concentrations in patients with heart failure, and the effects on left ventricular systolic and diastolic function were studied to determine the contribution of peripheral and central mechanisms to the haemodynamic effects. DESIGN: This was a single blind, randomised comparison of +/- candoxatrilat and placebo in patients with mild heart failure. All patients received two intravenous doses of +/- candoxatrilat and two placebo doses on four consecutive days. SETTING: A teaching hospital department of cardiology. PATIENTS: Six men (mean age 52 years) with mild heart failure (New York Heart Association class II) due to ischaemic heart disease (four patients) or dilated cardiomyopathy (two patients) were included. Mean ejection fraction was 37.5% and mean peak oxygen consumption was 20.4 ml/min/kg. MAIN OUTCOME MEASURES: Plasma ANF concentrations, haemodynamic indices and left ventricular diastolic function measured by early to atrial filling rate (E:A ratio) with Doppler echocardiography were determined before and after +/- candoxatrilat and placebo. RESULTS: +/- Candoxatrilat caused a threefold rise of plasma ANF compared with placebo (p < 0.005), but there was no significant change in heart rate, blood pressure, or cardiac output. Mean right atrial pressure fell from 6.7 to 4.7 mmHg (NS) and pulmonary artery wedge pressure fell from 9.2 to 6.7 mmHg (p < 0.05). Doppler echocardiographic measurements of transmitral blood flow showed a significant fall in peak early left ventricular filling velocity from 39.5 to 34.2 cm/s (p < 0.05), along with a non-significant rise in peak atrial filling velocity from 39.7-41.6 cm/s after +/- candoxatrilat. The E:A ratio, a Doppler index of left ventricular diastolic function, fell from a mean of 1.04 to 0.87 (p < 0.05). CONCLUSIONS: +/- Candoxatrilat increased plasma ANF concentrations and reduced right atrial and pulmonary artery wedge pressures. No evidence of an improvement in left ventricular systolic or diastolic function was found, so the fall in preload was due to peripheral effects, either an increase in venous capacitance or a fall in circulating blood volume.

Atrial Natriuretic Factor↗
PubMed1991

Monovalent cation induced structural transitions in telomeric DNAs: G-DNA folding intermediates.

Telomeric DNA consists of G- and C-rich strands that are always polarized such that the G-rich strand extends past the 3' end of the duplex to form a 12-16-base overhang. These overhanging strands can self-associate in vitro to form intramolecular structures that have several unusual physical properties and at least one common feature, the presence of non-Watson-Crick G.G base pairs. The term "G-DNA" was coined for this class of structures (Cech, 1988). On the basis of gel electrophoresis, imino proton NMR, and circular dichroism (CD) results, we find that changing the counterions from sodium to potassium (in 20 mM phosphate buffers) specifically induces conformational transitions in the G-rich telomeric DNA from Tetrahymena, d(T2G4)4 (TET4), which results in a change from the intramolecular species to an apparent multistranded structure, accompanied by an increase in the melting temperature of the base pairs of greater than 25 degrees, as monitored by loss of the imino proton NMR signals. NMR semiselective spin-lattice relaxation rate measurements and HPLC size-exclusion chromatography studies show that in 20 mM potassium phosphate (pH 7) buffer (KP) TET4 is approximately twice the length of the form obtained in 20 mM sodium phosphate (pH 7) buffer (NaP) and that mixtures of Na+ and K+ produce mixtures of the two forms whose populations depend on the ratio of the cations. Since K+ and NH4+ are known to stabilize a parallel-stranded quadruplex structure of poly[r(I)4], we infer that the multistranded structure is a quadruplex. Our results indicate that specific differences in ionic interactions can result in a switch in telomeric DNAs between intramolecular hairpin-like or quadruplex-containing species and intermolecular quadruplex structures, all of which involve G.G base pairing interactions. We propose a model in which duplex or hairpin forms of G-DNA are folding intermediates in the formation of either 1-, 2-, or 4-stranded quadruplex structures. In this model monovalent cations stabilize the duplex and quadruplex forms via two distinct mechanisms, counterion condensation and octahedral coordination to the carbonyl groups in stacked planar guanine "quartet" base assemblies. Substituting one of the guanosine residues in each of the repeats of the Tetrahymena sequence to give the human telomeric DNA, d(T2AG3)4, results in less effective K(+)-dependent stabilization. Thus, the ion-dependent stabilization is attenuated by altering the sequence. Upon addition of the Watson-Crick (WC) complementary strand, only the Na(+)-stabilized structure dissociates quickly to form a WC double helix.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Effect of captopril, an angiotensin-converting enzyme inhibitor, in patients with angina pectoris and heart failure.

The effects of captopril and placebo were compared in 18 patients with chronic heart failure and angina pectoris with use of a double-blind crossover trial design. Symptoms were assessed by patient treatment preference, visual analogue scores and nitroglycerin consumption. Exercise performance was assessed using two different treadmill protocols of different work intensity with simultaneous measurement of oxygen consumption and by supine bicycle exercise and simultaneous radionuclide ventriculography. Arrhythmias were assessed by 48 h ambulatory electrocardiographic monitoring. Patients generally preferred placebo to captopril, and this appeared to be due to an increase in symptoms of angina with captopril. Treadmill exercise time on a high intensity protocol was shorter with captopril than with placebo; on a low intensity protocol, angina became a more frequent limiting symptom even though overall exercise performance was not changed. The heart rate-blood pressure product was reduced, but largely because of a reduction in blood pressure rather than in heart rate. During supine bicycle exercise, no differences in symptoms, exercise performance, ejection fraction or changes in blood pressure were noted and ventricular arrhythmias were reduced. Captopril does not appear to be clinically useful in alleviating angina pectoris in patients with heart failure, and this effect may be related to a decrease in coronary perfusion pressure. Nonetheless, desirable metabolic effects, a reduction in arrhythmias and potential effects on survival require further study of captopril in patients with both angina and heart failure.

Aged↗
PubMed1991

Submaximal, but not maximal, exercise testing detects differences in the effects of beta-blockers during treadmill exercise: a study of celiprolol and atenolol. II.

Celiprolol is a new-generation beta-blocker with ancillary properties that include partial beta 2-agonism and direct vasodilating activity. The effects of atenolol and celiprolol on maximal exercise capacity and on both respiratory variables and subjective indices of breathlessness and fatigue during submaximal exercise were compared in a placebo-controlled crossover study of 12 trained volunteers. Both atenolol and celiprolol equally and significantly reduced exercise capacity and maximal oxygen consumption. During constant submaximal exercise at 70% maximal oxygen uptake, however, differences emerged between the two beta-blockers. Atenolol was associated with a significantly higher minute ventilation than placebo. In contrast, values for minute ventilation and respiratory exchange ratio with celiprolol were similar to values with placebo. During the early stages of exercise, treatment with atenolol was also associated with higher scores for the subjective indices of breathlessness and fatigue. Thus submaximal exercise, which may be physiologically more relevant to the everyday activities of patients, may demonstrate potentially useful differences between drugs that are not seen during maximal exercise testing.

Adrenergic beta-Antagonists↗
PubMed1991

Pancreatic beta-cell-type-specific transcription of the insulin gene is mediated by basic helix-loop-helix DNA-binding proteins.

The pancreatic beta-cell-specific expression of the insulin gene is mediated, at least in part, by the interaction of unique trans-acting beta-cell factors with a cis-acting DNA element found within the insulin enhancer (5'-GC CATCTG-3'; referred to as the insulin control element [ICE]) present in the rat insulin II gene between positions -100 and -91. This sequence element contains the consensus binding site for a group of DNA-binding transcription factors called basic helix-loop-helix proteins (B-HLH). As a consequence of the similarity of the ICE with the DNA sequence motif associated with the cis-acting elements of the B-HLH class of binding proteins (CANNTG), the ability of this class of proteins to regulate cell-type-specific expression of the insulin gene was addressed. Cotransfection experiments indicated that overexpression of Id, a negative regulator of B-HLH protein function, inhibits ICE-mediated activity. Antibody to the E12/E47 B-HLH proteins attenuated the formation, in vitro, of a previously described (J. Whelan, S. R. Cordle, E. Henderson, P. A. Weil, and R. Stein, Mol. Cell. Biol. 10:1564-1572, 1990) beta-cell-specific activator factor(s)-ICE DNA complex. Both of these B-HLH proteins (E12 and E47) bound efficiently and specifically to the ICE sequences. The role of B-HLH proteins in mediating pancreatic beta-cell-specific transcription of the insulin gene is discussed.

Animals↗
PubMed1991

Insulin gene expression in nonexpressing cells appears to be regulated by multiple distinct negative-acting control elements.

Selective transcription of the insulin gene in pancreatic beta cells is regulated by its enhancer, located between nucleotides -340 and -91 relative to the transcription start site. Transcription from the enhancer is controlled by both positive- and negative-acting cellular factors. Cell-type-specific expression is mediated principally by a single cis-acting enhancer element located between -100 and -91 in the rat insulin II gene (referred to as the insulin control element [ICE]), which is acted upon by both of these cellular activities. Analysis of the effect of 5' deletions within the insulin enhancer has identified a region between nucleotides -217 and -197 that is also a site of negative control. Deletion of these sequences from the 5' end of the enhancer leads to transcription of the enhancer in non-insulin-producing cells, even though the ICE is intact. Derepression of this ICE-mediated effect was shown to be due to the binding of a ubiquitously distributed cellular factor to a sequence element which resides just upstream of the ICE (i.e., between nucleotides -110 and -100). We discuss the possible relationship of these results to cell-type-specific regulation of the insulin gene.

Animals↗