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Biomedical subjects

G J Jones

Publications and source records attributed to G J Jones.

At least 37 records · Page 2Linked to original sources
PubMed1993

Amplification and expression of the TGF-alpha, EGF receptor and c-myc genes in four human oesophageal squamous cell carcinoma lines.

We have previously shown that four human oesophageal squamous cell carcinoma (SCC) cell lines secrete significant quantities of transforming growth factor alpha (TGF-alpha) in vitro. Three of these lines are known to produce supernumerary low-affinity epidermal growth factor receptors (EGF-Rs). Using an 125I-EGF competitive binding assay and Scatchard analysis, we show that the fourth also overproduces low-affinity receptors. According to slot blot DNA analyses, the secretion of high levels of TGF-alpha is not associated with amplification of the TGF-alpha gene, and hyperproduction of the EGF-R is correlated with receptor gene amplification. Western blot analyses show that the c-Myc protein is overexpressed in two of the cell lines; and Southern and Northern blot analyses indicate that this overexpression occurs independently of c-myc gene amplification. Our results are consistent with an autocrine role for TGF-alpha and EGF-R in oesophageal carcinogenesis and support the possibility that c-myc overexpression may be required for the in vivo tumourigenicity of cells that produce high levels of TGF-alpha and the EGF-R.

Adenocarcinoma↗
PubMed1993

Visual pigment bleaching in isolated salamander retinal cones. Microspectrophotometry and light adaptation.

Visual pigment bleaching desensitizes rod photoreceptors greatly in excess of that due to loss of quantum catch. Whether this phenomenon also occurs in cone photoreceptors was investigated for isolated salamander red-sensitive cones. In parallel experiments, (a) visual pigment depletion by steps of bleaching light was measured by microspectrophotometry, and (b) flash sensitivity was measured by recording light-sensitive membrane current. In isolated cones, visual pigment bleaching permanently reduced flash sensitivity significantly below that due to the reduction in quantum catch, and there was little spontaneous recovery of visual pigment. The "extra" desensitization due to bleaching was most prominent up to bleaches of approximately 80% visual pigment and reached a level approximately 1 log unit beyond that due to loss of quantum catch. At higher bleaches, the effect of loss of quantum catch became more important. Bleaching did not greatly reduce the maximum light-suppressible membrane current. A 99% reduction of the visual pigment permanently reduced the circulating current by only 30%. Visual pigment bleaching speeded up the kinetics of dim flash responses. All electrical effects of bleaching were reversed on exposure to 11-cis retinal, which probably caused visual pigment regeneration. Light adaptation in photopic vision is known to involve significant visual pigment depletion. The present results indicate that cones operate with a maintained circulating current even after a large pigment depletion. It is shown how Weber/Fechner behavior may still be observed in photopic vision when the contributions of bleaching to adaptation are included.

Absorptiometry, Photon↗
PubMed1992

The acute effects of low-intensity exercise on plasma lipids in endurance-trained and untrained young adults.

The acute effects of low-intensity exercise on plasma lipids were assessed in 22 healthy, normolipidaemic volunteers [mean age (SEM) 21.1 (0.2) years] of whom 11 were untrained and 11 endurance trained. Each subject walked for 2 h on a treadmill at a speed selected to elicit 30% [29.8 (3.9)%] of his or her maximal oxygen uptake. All subjects consumed a similar diet, i.e. 48% of energy from carbohydrate, for 2 days prior to the test. Pre-exercise, high-density lipoprotein (HDL) cholesterol concentration was higher in the trained group than in the untrained group [0.88 (0.06) mmol.l-1 vs 0.73 (0.09) mmol.l-1, P less than 0.05]. The walk elicited an increase in blood lactate concentration (P less than 0.01) but glucose homeostasis was well maintained by both groups. After 2 h of walking total cholesterol had increased by 13 (0.6)% (P less than 0.05). HDL cholesterol concentration increased by 17 (1.6)%, so that the ratio of total to HDL cholesterol was lower after the walk than pre-exercise (P less than 0.05). In the endurance-trained group HDL cholesterol concentration increased progressively, being 7.9 (2.4)% higher after 1 h and 19.7 (1.6)% higher after 2 h. A different response was evident in the untrained group where a rise after the 1st h [25.1 (2.3)%] was followed by a decrease towards pre-exercise values. These results show that one prolonged bout of low-intensity exercise modifies lipoprotein metabolism and hold out the interesting possibility that this response may differ in trained and untrained individuals.

Adolescent↗
PubMed1992

In vitro secretion of transforming growth factor alpha (TGF-alpha): a comparison of the A431 cell line with three human oesophageal squamous cell carcinoma lines.

Transforming growth factor alpha (TGF-alpha) is a single chain polypeptide which exists in a variety of forms differing in molecular weight. These forms are variously present in normal and neoplastic cells. Of particular interest are TGF-alpha's well-known mitogenic properties. The transition from a normal to a neoplastic cellular state results from signalling defects that may depend upon, inter alia, abnormal levels of expression and secretion of TGF-alpha. It is known that the secretion of TGF-alpha may be enhanced appreciably by agents such as phorbol 12-myristate 13-acetate (PMA), serum factors and epidermal growth factor (EGF). Here, we compare the efficacy of these three agents in the elevation of TGF-alpha secretion in the well studied A431 cell line with their previously undocumented efficacy in certain interesting, but little known, human oesophageal squamous cell carcinoma (SCC) lines.

Carcinoma, Squamous Cell↗
PubMed1992

Light-dependent delay in the falling phase of the retinal rod photoresponse.

Using suction electrodes, photocurrent responses to 100-ms saturating flashes were recorded from isolated retinal rods of the larval-stage tiger salamander (Ambystoma tigrinum). The delay period (Tc) that preceded recovery of the dark current by a criterion amount (3 pA) was analyzed in relation to the flash intensity (If), and to the corresponding fractional bleach (R*0/Rtot) of the visual pigment; R*0/Rtot was compared with R*s/Rtot, the fractional bleach at which the peak level of activated transducin approaches saturation. Over an approximately 8 ln unit range of I(f) that included the predicted value of R*s/Rtot, Tc increased linearly with ln I(f). Within the linear range, the slope of the function yielded an apparent exponential time constant (tau c) of 1.7 +/- 0.2 s (mean +/- S.D.). Background light reduced the value of Tc measured at a given flash intensity but preserved a range over which Tc increased linearly with ln I(f); the linear-range slope was similar to that measured in the absence of background light. The intensity dependence of Tc resembles that of a delay (Td) seen in light-scattering experiments on bovine retinas, which describes the period of essentially complete activation of transducin following a bright flash; the slope of the function relating Td and ln flash intensity is thought to reflect the lifetime of photoactivated visual pigment (R*) (Pepperberg et al., 1988; Kahlert et al., 1990). The present data suggest that the electrophysiological delay has a similar basis in the deactivation kinetics of R*, and that tau c represents TR*, the lifetime of R* in the phototransduction process. The results furthermore suggest a preservation of the "dark-adapted" value of TR* within the investigated range of background intensity.

Ambystoma↗
PubMed1991

Interactions between rat prolactin gene promoter and enhancer regions in mammosomatotrope and lactotrope cell lines.

Although both promoter and enhancer sequences of the PRL gene 5'-flanking DNA are required for cell-specific, high level expression in transgenic animals, reports of the relative contributions of these elements determined in transient transfection experiments have varied. In this study we examined the transcriptional activities of proximal promoter (-422/+33) and distal enhancer (-1956/-1530) sequences of the rat (r) PRL gene by transient transfection of hybrid genes containing these sequences into two rat pituitary cell lines, GC and 235-1. These cell lines exhibit characteristics either of mammosomatotropes, which express both PRL and the evolutionarily related GH gene (GC), or lactotropes, which express only PRL (235-1). As lactotropes are thought to differentiate from a mammosomatotrope precursor cell, comparisons between these cell lines provide the opportunity to examine the mechanisms that activate PRL and GH genes during development. We show that the relative contributions of promoter and enhancer elements differ between GC and 235-1 cells. Although maximal enhancer-driven activity was similar between these cell lines, promoter sequences were more active in GC (5-10% maximal) than 235-1 cells (1-2% maximal). However, no apparent differences in factor binding to the rPRL promoter region could be correlated with differences in activity, suggesting that differential factor modification, rather than different factors, is involved. As the rGH promoter exhibited a similar pattern of activity in these cell lines, these observations suggest that promoter as well as enhancer elements contribute to the cell specificity of PRL and GH gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Retinoid requirements for recovery of sensitivity after visual-pigment bleaching in isolated photoreceptors.

After visual-pigment bleaching, single isolated rod photoreceptors of Ambystoma tigrinum recover their sensitivity to light when supplied with 11-cis-retinal from liposomes or with 11-cis-retinal bound to interphotoreceptor retinoid-binding protein. Bleached rods do not recover sensitivity, or do so only very slowly, after exposure to 11-cis-retinol. The latter retinoid is "toxic" in that rods actually lose sensitivity in its presence. In contrast, bleached isolated cone cells recover sensitivity when either retinoid is supplied. It is suggested that the major pathway for rhodopsin regeneration during dark adaptation in the intact eye is transport of 11-cis-retinal from the pigment epithelium to the retina. The results also suggest that there may be separate pathways for visual-pigment regeneration in rods and cones during dark adaptation.

Ambystoma↗
PubMed1989

Membrane current responses of skate photoreceptors.

Light-evoked membrane currents were recorded with suction electrodes from the outer segments of individual photoreceptors enzymatically dissociated from the skate retina. The intensity-response relation of dark-adapted cells closely followed a Michaelis function for which a half-saturating response was elicited by a flash intensity that produced about 36 photoisomerizations. Dim-light responses, as well as the early rising phase of the responses to a wide range of flash intensities, could be described by a reaction scheme that involved a series of four first-order delay stages. The number of delay stages required to model the rising phase of the photocurrents did not change in light adaptation. However, background illumination that reduced sensitivity by 1.5 log units, or a bleaching exposure that resulted in a nearly equivalent desensitization, shortened significantly the time scale of the responses. In both instances there were two- to threefold increases in the rate constants of the transitional delays, and almost complete suppression of the tail current that characterized the response of the dark-adapted cell. These findings suggest that although light adaptation alters the gain and kinetics of the transduction mechanism, the nature of the intervening processes is the same in dark- and light-adapted photoreceptors. Moreover, the results show clearly that there is no need to postulate the existence of a second class of cone-like rods to account for the remarkable ability of skate photoreceptors to respond to incremental stimuli presented on "saturating" background fields or after exposure to an intense bleaching light.

Action Potentials↗
PubMed1988

Plasmalemma redox activity in the diatom thalassiosira: a possible role for nitrate reductase.

Plasmalemma redox activity in the diatom Thalassiosira is competitively inhibited by antiserum prepared against algal nitrate reductase (NR), and fluorescent labeling experiments reveal the binding of NR antiserum to the cell surface. Furthermore, the external electron acceptor Cu bathophenanthroline disulfonate causes immediate inhibition of intracellular primary amine production. A model is proposed in which plasmalemma-bound nitrate reductase reduces extracellular electron acceptors and intracellular nitrate and also acts as a trans-plasmalemma proton pump.

Journal Article↗
PubMed1987

The response to monochromatic light flashes of the oxygen consumption of honeybee drone photoreceptors.

Local measurements of the fall in oxygen pressure on stimulation of slices of the retina of the honeybee drone by flashes of light were made with oxygen microelectrodes and used to calculate the kinetics of the extra oxygen consumption (delta QO2) induced by each flash. The action spectrum for delta QO2 was obtained from response-intensity curves in response to brief (40 ms) monochromatic light flashes. The action spectrum of receptor potentials was obtained with the same experimental conditions. The two action spectra match closely: they deviate slightly from the photosensitivity spectrum of the drone rhodopsin (R). The deviation is thought to be due to wavelength-dependent light scattering and absorption in the preparation. In these experiments, the visual pigment was first illuminated with orange light, which is known to convert the bistable drone photopigment predominantly to the R state from the metarhodopsin (M) state. When long (300-900 ms) light flashes were used to elicit delta QO2, the responses to different wavelengths could not be matched in time course (as for the short flashes). Flashes producing large R-to-M conversions produced a prolonged delta QO2. The prolongation did not occur after double flashes, which produced both large R-to-M and M-to-R conversions. Similar changes in the length of afterpotentials in the photoreceptor cells and in a long-lasting decrease in photoreceptor intracellular K+ activity were found after long single or double flashes. The results are interpreted to show that the initial event for stimulation by light of metabolism in the drone retina is the same as that for stimulation of electrical responses (i.e., absorption of photons by R). Absorption of photons by M can produce an inhibitory effect on this stimulation.

Animals↗
PubMed1986

Safety and tolerance of recombinant interferon alfa-2a (Roferon-A) in cancer patients.

Recombinant interferon alfa-2a (Roferon-A, Hoffmann-La Roche Inc., Nutley, NJ) has been evaluated in clinical trials of more than 1300 patients with a broad spectrum of oncologic disease. Patients with either solid tumors or hematologic malignancies were treated with daily or three-times-weekly intramuscular injections for induction periods ranging from 8 to 16 weeks. Doses ranged from 1 X 10(6) units to 124 X 10(6) units per injection. When administered in low daily doses (approximately 3 X 10(6) units), Roferon-A was well tolerated, and dose attenuation was rarely required. Change to three-times-weekly treatment regimen at the same dose was usually sufficient to control toxicity when it occurred in this group of low-dose patients. Those patients receiving higher doses frequently required dose attenuation to 50% of the starting dose to improve clinical tolerance. Virtually all patients treated with Roferon-A experienced some degree of acute toxicity manifested as fever, chills, myalgia, and/or headache. These reactions usually occurred with initial dosing and frequently improved spontaneously with continued administration of the drug. Acetaminophen pretreatment was generally useful in ameliorating these symptoms. Common adverse experiences occurring after repeated dosing included fatigue, anorexia, and weight loss. Serious adverse reactions including cardiovascular and neurologic toxicity have occurred infrequently, primarily at higher doses. Hematologic toxicity and elevations in liver function parameters were also observed, but rarely required dose attenuation. Adverse effects were usually reversible after dose reduction or discontinuation of therapy. Approximately 27% of all patients developed antibodies to rHuIFN-alpha 2A during treatment. No adverse clinical sequelae have been associated with antibody development to date.

Adolescent↗
PubMed1985

Light-dependent reduction of copper(II) and its effect on cell-mediated, thiol-dependent superoxide production.

The thiol-dependent reduction of copper(II) and associated superoxide radical production in copper(II)-treated cultures of the unicellular alga Dunaliella tertiolecta is induced by light of wavelength greater than 425 nm. We propose that the effect of light on these reactions is mediated at the copper(II) reduction step through a light-stimulated ligand to metal charge transfer reaction between sulphur and copper(II). These results suggest that light may be an important controlling factor in metal-induced lipid peroxidation reactions.

Chloromercuribenzoates↗
PubMed1985

The effect of surgery with cardiopulmonary bypass on alveolar-capillary barrier function in human beings.

We measured the rate of clearance of technetium 99m-labeled diethylenetriamine pentaacetate (99mTcDTPA) (molecular weight, 492 daltons) from the lung into the blood (T1/2LB) in 9 patients before and after operation with cardiopulmonary bypass (CPB). Two hours postoperatively, T1/2LB fell from 49.3 +/- 13.6 minutes (mean +/- standard deviation) to 24.0 +/- 12.8 minutes (p less than 0.001). In addition, alveolar-arterial oxygen tension difference P(A-a)O2 had increased from 73 +/- 28 mm Hg to 164 +/- 37 mm Hg (p less than 0.001). The rates of clearance of 99mTcDTPA had returned to preoperative times by 7 days after operation, although there was still a significant (p less than 0.05) elevation in P(A-a)O2. Postoperative respiratory failure developed in 1 patient. The only abnormality of lung function detected preoperatively was an increased clearance rate for 99mTcDTPA (T1/2LB, 18 minutes). This study has shown an increased clearance from the lung of a low-molecular-weight molecule following operation with CPB. This finding should allow a more rational approach to elucidating the mechanisms of injury to the gas-blood interface in the lung following this type of operation.

Aged↗
PubMed1985

Recombinant leukocyte A interferon in B-cell chronic lymphocytic leukemia: in vivo effects on autologous antitumor immunity.

Eight previously treated and four untreated patients with B cell chronic lymphocytic leukemia (CLL) received 20 X 10(6) U/m2 recombinant leukocyte interferon clone A (rIFN-alpha A) intramuscularly three times a week for 8 weeks. None of the eight patients who had received prior chemotherapy exhibited objective evidence of tumor regression. Two of the four previously untreated patients responded with transient (90%) decreases in absolute lymphocyte counts lasting for 2 and 7 months. Toxicity was moderate, with all patients experiencing a flu-like syndrome requiring a 50% dose reduction. Half of the patients exhibited anorexia, weight loss, and a drop in performance status. The two responders had normal serum immunoglobulin levels prior to treatment, whereas 80% of non-responders had depressed levels. Treatment with rIFN-alpha A was associated with a depression of nonspecific and specific humoral immunity in assays employing cryopreserved autologous pretherapy CLL cells. No consistent effects were demonstrable in cytolytic assays with purified peripheral blood T cells as effector cells, including one that utilized autologous CLL target cells. rIFN-alpha A has limited antitumor activity in B cell CLL which is restricted to untreated patients with an early stage of disease. With the assays employed it was not possible to demonstrate that rIFN-alpha A could augment autologous antitumor immunity.

Aged↗
PubMed1984

Involvement of intracellular calcium in the phosphate efflux from mammalian nonmyelinated nerve fibers.

Phosphate efflux was measured as the fractional rate of loss of radioactivity from desheathed rabbit vagus nerves after loading with radiophosphate . The effects of strategies designed to increase intracellular calcium were investigated. At the same time, the exchangeable calcium content was measured using 45Ca. Application of calcium ionophore A23187 increased phosphate efflux in the presence of external calcium in parallel with an increase in calcium content. In the absence of external calcium, there was only a late, small increase in phosphate efflux. For nerves already treated with the calcium ionophore, the phosphate efflux was sensitive to small changes in external calcium, in the range 0.2 to 2 mM calcium, whereas similar increases in calcium in absence of ionophore gave much smaller increases in phosphate efflux. Removal of external sodium (choline substitution) produced an initial increase in phosphate efflux followed by a fall. The initial increase in phosphate efflux was much larger in the presence of calcium, than in its absence. The difference was again paralleled by an increase in calcium content of the preparation, thought to be due to inhibition of Na/Ca exchange by removal of external sodium. Measurements of ATP content and ATP, ADP, phosphate and creatine phosphate ratios did not indicate significant metabolic changes when the calcium content was increased. Stimulation of phosphate efflux by an increase in intracellular calcium may be due to stimulation of phospholipid metabolism. Alternatively, it is suggested that stimulation of phosphate efflux is associated with the stimulation of calcium efflux, possibly by cotransport of calcium and phosphate.

Animals↗
PubMed1984

On estimating freezing times during tissue rapid freezing.

For the study of morphological changes that are associated with fast physiological processes, it is important to know the times at which the surface regions of specimens are frozen during rapid freezing. A simple physical model has been used to estimate the freezing times and the cooling rates at 10 micron depths in specimens. The calculations indicate that cooling rates in excess of 4 X 10(4) K s-1 are associated with freezing times of less than 0.5 ms. Using the same model, experimental measurements of freezing times at much larger depths have been extrapolated to a depth of 10 micron, the times obtained are 0.1-0.6 ms for freezing by rapid immersion in cryogenic liquids, and 0.1 ms or less for freezing on a metal block. It is concluded that the delay time between contact with a cryogenic source and specimen freezing is less than 0.5 ms. The uncertainty in the time of freezing may be larger than this, because of an uncertainty of about +/- 0.5 ms in determining the exact time of contact and, for freeze fracture studies, because of an uncertainty of up to 0.5 ms due to imprecision in the depth of fracture. At the same time it is estimated that the time during which freezing takes place may be as high as 250 microseconds, which can be taken as an upper limit for the resolution time for rapid freezing.

Freezing↗