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Biomedical subjects

C J Jones

Publications and source records attributed to C J Jones.

At least 91 records · Page 5Linked to original sources
PubMed1997

Clinical features of photodamaged human skin are associated with a reduction in collagen VII.

Chronically sun-exposed or photodamaged human skin is characterized by a number of clinical features, including wrinkles. However, little is known about the molecular mechanisms that underlie these features. We investigated the hypothesis that the mechanism of wrinkle formation may involve loss of anchoring fibrils, composed mainly of collagen VII, which are important in maintaining dermal-epidermal junction integrity. Ten volunteers with moderate to severe photodamage of dorsal forearm skin were recruited to the study. Using immunohistochemistry, transmission electron microscopy and in situ hybridization, we compared collagen VII protein and mRNA content of photodamaged forearm skin with that of sun-protected hip and upper inner arm skin from the same subjects. Numbers of anchoring fibrils per linear microns of basement membrane (mean +/- SEM) were significantly lower in photodamaged skin (1.79 +/- 0.10) as compared with sun-protected hip (2.28 +/- 0.11) and upper inner arm skin (2.21 +/- 0.10) (P < 0.01), and similarly keratinocyte expression of collagen VII mRNA, quantitated as number of positively stained keratinocytes per high power field, was significantly reduced in photodamaged skin (6.3 +/- 2.5) as compared with sun-protected hip (20.0 +/- 5.6) and upper inner arm skin (17.7 +/- 4.9) (P < 0.001). Semiquantitative assessment of immunohistochemical staining for collagen VII showed a non-significant reduction in photodamaged skin as compared with sun-protected skin. We propose that reduced content of collagen VII in photodamaged skin contributes to wrinkle formation by weakening the bond between the dermis and epidermis.

Aged↗
PubMed1997

The Q-switched neodymium:YAG laser and tattoos: a microscopic analysis of laser-tattoo interactions.

The Nd:YAG laser effectively removes or lightens amateur and professional tattoos. The biomechanics of the removal of tattoo particles at the cellular level are incompletely understood. We examined biopsies obtained from 35 amateur and professional tattoos (including coloured tattoos), treated on three or more occasions with the Nd:YAG laser. Biopsies taken immediately after laser treatment showed vacuolation with complete clearance of tattoo particles in the most superficial layers of the dermis, as assessed by light and electron microscopy. We propose that the 'disappearance' of the tattoo particle arises from the formation of atomic species and gaseous products, which are rapidly dissolved in the extracellular fluid. Residual fragmented particles that are commonly found in the mid- and lower dermis are rephagocytosed. The interaction between the Nd:YAG laser and black tattoo particles at 1064 nm, and red tattoo particles at 532 nm, appears to be specific, as there was little evidence of thermal damage to adjacent cells or stromal collagen.

Humans↗
PubMed1996

Activity and expression of Na(+)-K(+)-ATPase in human placental cytotrophoblast cells in culture.

1. To determine whether there is a change during differentiation, the activity and expression of Na(+)-K(+)-ATPase were studied in mononucleate cytotrophoblast cells (18 h culture) and syncytiotrophoblast-like cells (66 h culture). A choriocarcinoma-derived cell line (JAr) which, unlike the cytotrophoblast cells, divides in culture, was also studied for comparison. 2. Na(+)-K(+)-ATPase activity was assessed by measurement of ouabain-sensitive 86Rb+ uptake. Na(+)-K(+)-ATPase expression was determined by (i) measurement of [3H]ouabain binding and (ii) Northern hybridization to measure expression of alpha-1 and beta 1-subunit mRNA. 3. There was no significant difference in either activity or expression of Na(+)-K(+)-ATPase during differentiation of cytotrophoblast cells. However, expression of alpha 1- and beta 1-subunit mRNA was significantly lower in 66 vs. 18 h cultured cytotrophoblast cells. 4. Both Na(+)-K(+)-ATPase activity and [3H]ouabain binding was significantly greater in JAr cells than either cytotrophoblast cell groups, although expression of alpha 1- and beta 1-subunit mRNA was the same as cytotrophoblast cells cultured for 18 h. 5. It is concluded that N(+)-K(+)-ATPase activity and protein expression does not change during differentiation of cytotrophoblast cells but that there are changes in expression at the transcriptional or post-transcriptional level.

Blotting, Northern↗
PubMed1996

S phase cell-cycle arrest following DNA damage is independent of the p53/p21(WAF1) signalling pathway.

It is now likely that the cyclin-kinase inhibitor, p21(WAF1/SD11), is a key effector of p53-mediated cell-cycle arrest at the G(1)/S checkpoint following DNA damage. More recently, however, in vitro data has suggested that this pathway may also mediate the acute inhibition of DNA synthesis seen in cells already in S phase. Here we address this question in an intact cell system using normal human diploid fibroblasts in which p53 function is manipulated by expression of a dominant-negative mutant (ala(143)) introduced by a retroviral vector. Induction of DNA strand breaks in normal control fibroblasts by exposure to bleomycin led as expected to G(1)/S cell cycle arrest, induction of p2l(WAF1) and a rapid reduction in the rate of DNA synthesis in cells already in S phase. Stable expression of mutant p53 abrogated the G(1)/S (but not the G(2)/M) cell cycle checkpoint and abolished the induction of p21(WAF1), but had no significant effect on the inhibition of DNA replication in S phase nuclei. We conclude that, despite the in vitro evidence for inhibitory activity on PCNA/polymerase delta, p21(WAF1) induction does not appear to be essential for the acute inhibition of DNA synthesis in the intact cell following strand-break damage in S phase.

Antibiotics, Antineoplastic↗
PubMed1996

High frequency deletion of the tumour suppressor gene P16INK4a (MTS1) in human thyroid cancer cell lines.

p16INK4a (MTS1) is an important negative regulator of mammalian cell proliferation, acting via inhibition of CDK4/cyclin D-dependent phosphorylation of pRb to prevent progression through the G1 phase of the cell cycle. Loss of p16 activity by either gene deletion, mutation or transcriptional inactivation has now been found in a wide range of human cancers of both epithelial and mesenchymal origin, at a frequency rivalling that of p53 mutation. As a first step towards investigating its possible role as a tumour suppressor gene in thyroid tumorigenesis, we have carried out a Southern blot analysis of the p16 gene locus in a series of cell lines derived from differentiated human thyroid cancers. Homozygous deletion of the entire p16 coding sequence was observed in two of three follicular and two of four papillary cancer cell lines, but not in normal tissue or normal cells immortalised by SV40 T antigen. Given the co-existence of p16 abnormalities in primary tumours and cell lines observed in other tumour types, this high frequency of deletion suggests that p16 is a key tumour suppressor gene in the genesis of differentiated thyroid cancer.

Adenocarcinoma, Follicular↗
PubMed1996

Patterns of personality change across the life span.

Six aspects of personality were examined for a sample of 211 individuals across either a 30- or 40-year time span. Latent curve analyses found an underlying pattern of lifetime change for self-confidence, cognitive commitment, outgoingness, and dependability. An underlying pattern of lifetime stability was found for assertiveness. No shared systematic underlying pattern could be fit to individuals' lifetime trajectories for warmth. Although individuals shared a single underlying pattern of change or stability for 5 of the 6 dimensions of personality considered here, they also showed differences in the degree and direction of personality change.

Adolescent↗
PubMed1996

Altered release of endothelin-1,2 and thromboxane B2 from trophoblastic cells in pre-eclampsia.

The aim of the study was to investigate whether pre-eclampsia is associated with an altered release of vasoactive substances from trophoblastic cells in vitro. Trophoblastic cells from 15 uncomplicated control pregnancies and 18 pre-eclamptic pregnancies at preterm (weeks 31-36; n = 12) and term (weeks 37-40; n = 21) were cultured for 5 days. The concentrations of angiotensin II (AII), endothelin-1,2 (ET-1,2), thromboxane B2 (TXB2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and leukotriene B4 (LTB4) were measured daily in culture media for 5 days by radioimmunoassay. In pre-eclampsia, concentrations of ET-1,2 were decreased (P < 0.01) at both preterm and term, TXB2 concentrations were increased (P < 0.05) only at preterm and the TXB2-6-keto-PGF1 alpha ratio was increased at both preterm and term (P < 0.01) as compared with the controls. Concentrations of AII, 6-keto-PGF1 alpha and LTB4 were similar to the controls. The data suggest that pre-eclampsia is associated with a decreased release of ET-1 and an increased release of TXB2 from trophoblastic cells in vitro.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

In vivo and in vitro vasoactive reactions of coronary arteriolar microvessels to nitroglycerin.

The actions of nitroglycerin on the coronary microcirculation are controversial, with some laboratories reporting that coronary arterioles dilate to the drug and others reporting that they do not. Our goal was to reconcile these disparate observations. Specifically, we hypothesized that dilation of coronary arterioles by nitroglycerin is overwhelmed by intrinsic autoregulatory escape mechanisms. Accordingly, we projected that coronary arterioles would show transient, but not sustained, dilation to nitroglycerin in vivo. Furthermore, we hypothesized that isolated coronary arterioles would show sustained dilation to the drug, because intrinsic escape mechanisms would be absent under these conditions. To test these hypotheses, we measured diameter changes of canine coronary microvessels in vivo during continuous nitroglycerin administration (intracoronary infusion or epicardial suffusion) using intravital fluorescent microscopy (n = 17 dogs) at two time points: early (1-3 min), when coronary artery blood flow velocity was increased, and late (15-20 min), after blood flow velocity returned to control. Tb study responses of coronary arterioles in the absence of autoregulatory influences, we measured the diameter of isolated canine coronary arterioles to varying doses of nitroglycerin (n = 8 vessels, maximal diameter 81 +/- 4 microns). During the early phase of nitroglycerin infusion (1,3, and 10 micrograms.kg-1.min-1), coronary arterioles dilated by 4 +/- 1, 7 +/- 2, and 13 +/- 2% (all P < 0.05), whereas small arteries dilated by 1 +/- 2, 3 +/- 1, and 4 +/- 1%, respectively (P < 0.05 for the higher doses). Coronary artery blood velocity measured increased by 45 +/- 15% (3 micrograms.kg-1.min-1, P < 0.05). Suffusion of nitroglycerin (10(-5) M) dilated coronary arterioles, but not small arteries, by 17 +/- 5% (P < 0.05) between 1 and 3 min. After 15-20 min of nitroglycerin (3 micrograms.kg-1.min-1 by intracoronary infusion), diameters of coronary arterioles and coronary artery blood velocity returned to control, whereas dilation of small arteries remained significant at 4 +/- 1%. Coronary arteriolar dilation by epicardial suffusion of nitroglycerin also waned to control values by 15-20 min, whereas dilation of small arteries was observed: 5 +/- 2% (P < 0.05). In vitro, nitroglycerin caused dose-dependent dilation of coronary arterioles to their maximal diameter, which was sustained for 20 min. Thus nitroglycerin dilates coronary arterioles and small arteries. The dilation in vivo is transient for arterioles but sustained for arteries. In vitro, the dilation is sustained. Because microvessels in vitro are capable of sustaining dilation for 20 min, we conclude that the waning of arteriolar dilation in vivo is related to autoregulatory escape from dilation by nitroglycerin.

Animals↗
PubMed1996

Blood velocity profiles in the human renal artery by Doppler ultrasound and their relationship to atherosclerosis.

Blood velocity profiles were measured in the renal branch (diameter 5.9 +/- 1.3 mm) of the aortorenal bifurcation using a 20-MHz 80-channel pulsed Doppler velocimeter during retroperitoneal surgery in 10 patients. The peak Reynolds number was 1145 +/- 140 and the frequency parameter (Wormersley parameter) was 3.0 +/- 0.8. Immediately distal to the ostium of the renal artery, reverse flow, indicating flow separation, was observed near the cranial wall mainly during the first part of the cardiac cycle. There were flows from the cranial to the caudal side of the artery at this location, indicating the presence of strong secondary flows. Two diameters downstream of the ostium, the velocity profiles were skewed to the caudal side in all patients. Four diameters downstream, the flow profile was symmetrical (3 patients) or only slightly skewed (7 patients) and virtually parabolic throughout the cardiac cycle. These observations mean that the flow on the cranial side of the renal branch of the human aortorenal bifurcation is characterized by (1) a bidirectional oscillation of the flow, (2) separation of the flow during systole, and (3) low time-averaged shear rate. These blood velocity patterns may be related to the localization and development of atheromatous plaque that occurs preferentially in this region of the renal artery. Conversely, the unidirectional, axisymmetrical flow found in more distal parts of the renal artery are associated with a very low incidence of lesions.

Adult↗
PubMed1996

Decidual sialylation shows species-specific differences in the pregnant mouse and rat.

Biotinylated lectins from Sambucus nigra (SNA) and Maackia amurensis (MAA), which bind to alpha 2,6-linked and alpha 2,3-linked sialyl residues, respectively, were used as probes to study glycan terminal modifications associated with decidualization in the uterine stroma of pregnant rats and mice. Binding of lectins from Erythrina cristagalli (ECA), Phaseolus vulgaris (leukoagglutinin, L-PHA), Triticum vulgaris (WGA) and Bandeiraea simplicifolia (BSA-1B4) was also examined. Tissues from rats between day 5 and day 8 of gestation and mice between day 5 and day 7 of gestation were fixed in Bouin's solution and embedded in wax prior to lectin histochemistry. On day 7 in rats and day 6 in mice, there was a marked reduction in the binding of SNA in the subluminal decidua surrounding the implantation site. In rats, MAA binding to enlarged decidual cells around the implantation chamber was increased markedly, but there was no change in mice. In both species there was de novo binding of ECA in the SNA-negative area, suggesting that the loss of alpha 2,6-linked sialyl residues unmasks terminal N-acetyl lactosamine. These findings are consistent with previous evidence of a close structural and functional similarity between the artificially induced deciduoma and true decidua of rats and show identical changes to the glycosylation patterns previously found in differentiating rat deciduoma. In both species, therefore, decidua exhibits regionally specific terminal glycosylation. However, the species-specific expression of alpha 2,3-linked sialyl residues suggests distinct patterns of steroidally modulated sialyl transferase expression.

Animals↗
PubMed1995

Endothelial control of arterial distensibility is impaired in chronic heart failure.

BACKGROUND: Vascular tone is a determinant of conduit artery distensibility. The aim of this study was to establish whether endothelium-derived relaxing factor (EDRF) influences the distensibility of conduit arteries and whether endothelium-mediated increases in distensibility are impaired in chronic heart failure (CHF). METHODS AND RESULTS: Conduit artery distensibility was measured by two methods in healthy subjects and in nine patients with CHF caused by dilated cardiomyopathy. In the first method, pulse-wave velocity (PWV) was measured in the right common iliac artery at rest and during local infusions of acetylcholine (10(-7) to 10(-5) mol/L) or adenosine (2 x 10(-7) to 2 x 10(-5) mol/L), with correction for systemic effects. Acetylcholine induced concentration-dependent local reductions of PWV in healthy subjects (-5%, -15%, and -26%) but not in CHF patients (3%, 1%, -4%, P < .01), whereas adenosine induced similar reductions of PWV in healthy subjects and CHF patients. In the second method, brachial artery diameter, blood flow, and blood pressure were measured noninvasively by high-resolution ultrasound, continuous-wave Doppler, and photoplethysmography during reactive hyperemia in the hand and after sublingual glyceryl trinitrate (GTN, 400 micrograms). Hyperemic flow, similar in healthy subjects and CHF patients, was associated with increases in diameter and distensibility in healthy subjects (8.8% and 18.4%, respectively) but not in CHF patients (0.3% and -4.5%), whereas GTN induced similar effects in healthy subjects and CHF patients. CONCLUSIONS: These data indicate that conduit artery distensibility is increased by acetylcholine and increased blood flow in healthy subjects but not in CHF patients, whereas the effects of adenosine and GTN on distensibility are preserved in CHF patients. This implies that EDRF-mediated increases in distensibility are impaired in CHF patients, thus adding to cardiac work.

Acetylcholine↗
PubMed1995

Anti-(human immunodeficiency virus) activity of polyoxotungstates and their inhibition of human immunodeficiency virus reverse transcriptase.

Heteropolyoxotungstates of the Keggin class containing different heteroatoms were tested for inhibition of two strains of human immunodeficiency virus 1 (HIV-1); they exhibited varying antiviral activity. Compounds containing boron were inactive, only one of those containing phosphorus showed selective anti-viral activity, whereas all silicon-containing compounds exhibited significant anti-viral activity in C8166 cells infected with the IIIB strain. Their effectiveness was some 10-fold higher in JM cells with selectivity indices of about 2000. The silicotungstates were effective inhibitors of HIV reverse transcriptase, showing greater inhibition with RNA/DNA template primers than with DNA/DNA template.primer. Kinetic analysis demonstrated that they inhibit the enzyme by different mechanisms, as, of the four compounds examined, two competed with template.primer and two competed with deoxynucleoside triphosphate. Inhibition of DNA polymerase activity by these compounds was compared using polymerases from different sources, including human; although not necessarily most specific for HIV-1 reverse transcriptase, they did not inhibit all DNA polymerases to a similar degree.

Antiviral Agents↗
PubMed1995

Role of nitric oxide in the coronary microvascular responses to adenosine and increased metabolic demand.

BACKGROUND: The purpose of this study was to test the hypothesis that endothelium-derived nitric oxide (NO) participates in coronary microvascular responses to adenosine and pacing-induced increases in metabolic demand by maintaining an optimal distribution of coronary resistance. METHODS AND RESULTS: Coronary microvascular diameters were measured by stroboscopic epi-illumination and intravital microscopy in open-chest dogs (n = 20). Epicardial coronary blood velocity (CBV) was measured by Doppler flowmetry. Responses to adenosine (1 and 10 micrograms.kg-1.min-1 IC) and left atrial pacing (180 beats per minute) were recorded before and after inhibition of NO synthesis by NG-nitro-L-arginine methyl ester (L-NAME, 30 micrograms.kg-1.min-1 IC). At baseline, adenosine dilated arterioles (< 100 microns) (11 +/- 4% and 25 +/- 3% diameter changes, P < .05) more than small arteries (> 100 microns) (-4 +/- 6% and 7 +/- 3%, P < .05 for the higher dose) and increased CBV (43 +/- 31% and 118 +/- 25%, P < .05). Left atrial pacing dilated arterioles (12 +/- 2%, P < .05) and small arteries (8 +/- 3%, P < .05) and also increased CBV (68 +/- 9%, P < .05). L-NAME abolished CBV increases caused by acetylcholine (10 and 100 ng.kg-1.min-1 IC; 53 +/- 33% and 168 +/- 82% versus -12 +/- 15% and -1 +/- 14%, P < .05) but not papaverine. Small arteries were constricted by L-NAME (-8 +/- 2%, P < .05), arterioles were dilated (10 +/- 4%, P < .05), and CBV was unchanged. After L-NAME, adenosine failed to dilate arterioles further (3 +/- 3% and 2 +/- 2%; P < .05 versus prior responses), and CBV changes were attenuated (14 +/- 16% and 8 +/- 13%; P < .05 versus prior responses). Pacing also failed to dilate arterioles (-4 +/- 2%, P < .05 versus prior response), resulting in an attenuated CBV change (34 +/- 13%, P < .05 versus prior response). The possibility that adenosine stimulates NO release in canine coronary arterioles was investigated in isolated arterioles (diameters, 81 +/- 4 microns; n = 8). Adenosine caused dose-dependent dilation to maximal diameter, which was unaffected by inhibition of NO synthesis by L-NAME. CONCLUSIONS: Inhibition of NO synthesis attenuates coronary dilation during adenosine infusions and during pacing-induced increases in metabolic demand. Inhibition of NO synthesis may shift the major site of coronary resistance into small arteries through autoregulatory adjustments in arterioles. These data therefore suggest that NO, by dilating predominantly small coronary arteries, promotes metabolic coronary dilation by preserving the tone and vasodilator reserve of arterioles.

Adenosine↗