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Biomedical subjects

J A Fox

Publications and source records attributed to J A Fox.

At least 37 records · Page 2Linked to original sources
PubMed1995

A comparison of preferences for pork sandwiches produced from animals with and without somatotropin administration.

Experimental auction markets were designed and used to investigate consumer preferences for sandwiches produced with meat from pigs treated with porcine somatotropin. A second-price, sealed-bid auction procedure was used to determine willingness to pay to exchange a pork loin sandwich with leaner meat from pigs treated with somatotropin for a similar sandwich with meat from untreated pigs. The research was conducted using a sample of 114 undergraduate students in Iowa, Arkansas, Massachusetts, and California. At the end of the experiment 33 of 58 subjects would not bid to change their leaner pork for typical pork, whereas 15 of 56 subjects would not bid to change their typical pork for leaner pork. The results suggest a preference for leaner meat from the treated pigs, but also the potential for niche markets for meat and meat products from untreated pigs.

Animals↗
PubMed1994

Novel omega-conopeptides reduced field potential amplitudes in the rat hippocampal slice.

The synthetic omega-conopeptides SNX-111 (MVIIA), SNX-124 (GVIA), SNX-183 (SVIB), and SNX-185 (TVIA) reduced excitatory postsynaptic potential (EPSP) amplitudes measured in the stratum radiatum of rat hippocampal slices by about 50% at doses at or near 200 nM. These effects were at least partially reversible in most slices. EPSP amplitude was not further reduced at the highest concentrations of SNX-111, SNX-124, and SNX-185 (1.5-10 microM). In contrast, the highest concentrations of SNX-183 (2 and 10 microM) further reduced EPSP amplitude to about 20% of control. SNX-183 reduced EPSP amplitude in slices previously treated with maximally effective doses of SNX-111 or SNX-124. These results suggest that there are at least two classes of omega-conopeptide receptor sites that modulate neurotransmitter release in the rat hippocampus.

Animals↗
PubMed1994

Hydrolysis, absorption and metabolism of di(2-ethylhexyl) terephthalate in the rat.

1. The hydrolysis of di(2-ethylhexyl) terephthalate (DEHT) and di(2-ethylhexyl) phthalate (DEHP) were studied using rat gut homogenate fractions in vitro. Both isomers were hydrolysed by the intestinal fraction; however, DEHP was hydrolysed to 2-ethylhexanol (2-EH) and mono(2-ethylhexyl) phthalate (MEHP) in about equal proportions, whereas DEHT was hydrolysed to 2-EH and terephthalic acid (TPA). The half-lives for disappearance of the diesters were determined to be 12.6 min for DEHP and 53.3 min for DEHT. 2. The absorption and metabolism of DEHT were studied by administering [hexyl-2-14C]DEHT (in corn oil) by oral gavage at a dose level of 100 mg/kg to 10 adult male Sprague-Dawley rats. Urine, faeces and expired air were collected for 144 h and analysed for the presence of radioactivity, and faeces and urine were analysed for unlabelled metabolites. 3. Radioactivity was eliminated in faeces (56.5 +/- 12.1% of dose) primarily as unchanged DEHT, small amounts of MEHT and polar metabolites; excreted in urine (31.9 +/- 10.9% of dose) principally as MEHT and metabolic products of 2-EH; and expired as 14CO2 (3.6 +/- 0.9% of dose). Less than 2% of the administered radioactivity was found in the carcass. Small amounts of 14C were found in the tissues with the highest amounts found in liver and fat. 4. Metabolites identified in urine included terephthalic acid (equivalent to 51% of dose), oxidized metabolites of 2-EH and MEHT, and glucuronic and sulphuric acid conjugates (equivalent to about 10% of dose).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Consumer acceptability of milk from cows treated with bovine somatotropin.

Experimental auction markets were used to investigate the acceptability to undergraduate students of milk from cows treated with bST. The auction market was used to elicit willingness of participants to pay to exchange "bST milk" for "normal" milk when given repeated market participation. The results suggest that more than 60% of participants would purchase milk from cows treated with bST at economically feasible discounts.

Animals↗
PubMed1993

Strain specificity and binding affinity requirements of neutralizing monoclonal antibodies to the C4 domain of gp120 from human immunodeficiency virus type 1.

The binding properties of seven CD4-blocking monoclonal antibodies raised against recombinant gp120 of human immunodeficiency virus type 1 strain MN (HIV-1MN) and two CD4-blocking monoclonal antibodies to recombinant envelope glycoproteins gp120 and gp160 of substrain IIIB of HIVLAI were analyzed. With a panel of recombinant gp120s from seven diverse HIV-1 isolates, eight of the nine antibodies were found to be strain specific and one was broadly cross-reactive. Epitope mapping revealed that all nine antibodies bound to epitopes located in the fourth conserved domain (C4) of gp120. Within this region, three distinct epitopes could be identified: two were polymorphic between HIV-1 strains, and one was highly conserved. Studies with synthetic peptides demonstrated that the conserved epitope, recognized by antibody 13H8, was located between residues 431 and 439. Site-directed mutagenesis of gp120 demonstrated that residue 429 and/or 432 was critical for the binding of the seven antibodies to gp120 from HIV-1MN. Similarly, residues 423 and 429 were essential for the binding of monoclonal antibody 5C2 raised against gp120 from HIV-1IIIB. The amino acids located at positions 423 and 429 were found to vary between strains of HIV-1 as well as between molecular clones derived from the MN and LAI isolates of HIV-1. Polymorphism at these positions prevented the binding of virus-neutralizing monoclonal antibodies and raised the possibility that HIV-1 neutralization serotypes may be defined on the basis of C4 domain sequences. Analysis of the binding characteristics of the CD4-blocking antibodies demonstrated that their virus-neutralizing activity was directly proportional to their gp120-binding affinity. These studies account for the strain specificity of antibodies to the C4 domain of gp120 and demonstrate for the first time that antibodies to this region can be as effective as those directed to the principal neutralizing determinant (V3 domain) in neutralizing HIV-1 infectivity.

Amino Acid Sequence↗
PubMed1993

'The high price of hips'. Whose name is on the bill?

Many of hospital's more secret corners have been the subject of television exposés in the past 12 months and it was probably long overdue that the validity of joint replacement should finally come under scrutiny. Public Eye did just this (BBC2, February 26th 1993), investigating the number of revision hip arthroplasties that are becoming necessary in the UK--some 12% at the last report with a projected increase over the next two years to a massive 30%. The likely repercussions from this and the inability of our groaning health service to cope with the influx, are truly staggering and will mean that people waiting for primary replacements will simply wait longer and longer.

Hip Prosthesis↗
PubMed1992

Voltage-dependent currents in isolated cells of the turtle retinal pigment epithelium.

The electrophysiological properties of isolated turtle retinal pigment epithelial cells (RPE cells) were investigated using the whole-cell patch-clamp technique. Most RPE cells exhibited a voltage-dependent outward current activated by depolarization beyond about -43 mV that inactivated during a 500-ms voltage step. Tail current measurements indicated that the conductance underlying this current was potassium selective. This current inactivated with prolonged depolarization and was abolished or reduced by extracellular quinidine, barium, tetraethylammonium (TEA) and 4-aminopyridine (4-AP). Steady-state inactivation of the voltage-dependent outward current revealed a time-independent outwardly rectifying current/voltage relationship in many cells. In addition, many cells had an outward current that activated slowly upon depolarization beyond about +40 mV and appeared to reverse near 0 mV in both 3 mM KCl and 30 mM KCl external solutions. This current was often observed in the presence of potassium channel blockers. Hyperpolarizing pulses commonly evoked inward currents that activated slowly and did not inactivate. These currents were commonly observed when fluoride was absent from the pipette, and only occasionally when fluoride was the major pipette anion. Tail current measurements indicated that this current was somewhat anion selective. These currents may play important roles in the homeostatic and phagocytic functions of RPE cells in their interactions with the neural retina.

Animals↗
PubMed1991

Examination of subconductance levels arising from a single ion channel.

Single-channel records often show frequent currents at a main conductance level and occasional currents at subconductance levels. In some instances, the conductances occur at regular levels that are multiples of a minimum conductance. It is well-appreciated that multiple conductance levels may arise either from the co-operative gating of more than one pore or from changes that occur in a single pore. In this paper, we used theoretical models of ion permeation to examine subconductances arising in a single-pore channel. In particular, the work focuses on the following question: how can an ion channel that provides only one aqueous pore through the membrane produce regular subconductances and a main conductance that all have the same selectivity and the same ion binding affinity? The three types of ion permeation models used in this study showed that a single-pore channel can have subconductances because of long-lived conformational states, because of alterations in rapid fluctuations between conformational states, or because of slight alterations in the electrostatic properties in the channel's entrance vestibules. Regular subconductances with the same selectivity and binding affinity can arise in a single pore even if the energy profile changes do not meet the constant peak offset condition. The results show that the appearance of regular subconductance levels in a single-channel recording is not sufficient evidence to conclude that identical pores have co-operative gating, as would arise in a channel that is a multi-pore complex.

Animals↗
PubMed1991

Immunoblot studies to analyze antibody to the Rickettsia typhi group antigen in sera from patients with acute febrile cerebrovasculitis.

In 1986, an unusual syndrome of acute febrile cerebrovasculitis in the Piedmont Region of Virginia was reported. All patients had encephalopathy and prior exposure to both a sylvan environment and flea-infested animals. The initial serological studies suggested a rickettsial origin, corroborating clinical, epidemiological, and histopathological findings. Sera from four of five patients were subsequently studied by immunoblotting. Unabsorbed and absorbed sera were tested with electrophoresed and electroblotted Rickettsia typhi, Legionella bozemanii, and Proteus vulgaris OX19 antigens. The unabsorbed sera reacted with all three antigens. The P. vulgaris- and L. bozemanii-absorbed sera reacted with R. typhi only and without significantly less intensity. In contrast, the reactivity of R. typhi-absorbed sera was significantly lower with all three antigens. These results indicate that these patients had specific antibodies to a typhus group antigen. Although our findings suggest that a rickettsia of the typhus group may have caused this syndrome, no definitive diagnosis could be achieved because a rickettsial organism was not isolated.

Acute Disease↗
PubMed1990

Jejunal circular muscle motility is decreased in nematode-infected rat.

Jejunal circular muscle motility was studied in vitro in rats 8-10 days after inoculation with the inflammation-inducing nematode Nippostrongylus brasiliensis. The passive properties of the muscle, i.e., the development of passive tension and the optimal amount of stretch for active contractions, were unchanged by infection. Infection decreased the development of active resting tension, spontaneous contractions, muscle contraction to muscarinic receptor activation, and direct electrical stimulation. Relaxation to beta-adrenergic stimulation was also decreased in tissues from infected animals. Response to cholinergic stimulation, spontaneous contractions, and active resting tension were completely dependent on extracellular calcium. The dominant response to electrical stimulation of intrinsic nerves was relaxation in control tissue and contraction in tissue from infected rats. In the presence of atropine, all tissues from control rats but only 33% of the tissues from infected rats relaxed, suggesting a marked difference in functional inhibitory innervation. The inflammation may have either decreased the circular muscle responsiveness to the inhibitory transmitter or decreased the release of this transmitter. Thus, a nematode infection produces decreased responsiveness of the intestinal circular muscle to both contracting and relaxing stimuli and causes a reduction in functional inhibitory innervation in this layer. These changes suggest mechanisms for the reduction of intestinal transit observed after some nematode infections.

Animals↗
PubMed1990

Pertussis toxin-sensitive and -insensitive mechanisms for diacylglycerol-protein kinase C signalling during insulin action in BC3H-1 myocytes.

The findings reported herein indicate that insulin rapidly perturbs phospholipid metabolism and consequent intracellular signalling, in its target tissues by two fully separable mechanisms. One of these mechanisms involves a pertussis toxin-sensitive Gi alpha, which probably serves to couple the insulin receptor to a PI-glycan phospholipase C, which, in turn, leads to the release of HGM and consequent activation of de novo PA synthesis. The second mechanism is PC hydrolysis, which is pertussis toxin-insensitive. Both mechanisms serve as important sources of DAG during insulin action, and PKC appears to be activated by DAG derived from both pathways. Although DAG may be derived from each of these signalling pathways, it is clear that PI-glycan HGM will only be derived from pertussis toxin-sensitive PI-glycan hydrolysis. These findings may help to explain why some, but not all, insulin effects are inhibited by pertussis toxin and are therefore apparently dependent upon Gi alpha. Whether or not other G-proteins are important in other phospholipid signalling pathways during insulin action, e.g., PC hydrolysis, remains to be determined.

Animals↗
PubMed1989

Phosphorylation of fructose bisphosphate aldolase in Trypanosoma brucei.

Methods were developed for in vivo labelling of trypanosome proteins with inorganic phosphate and the labelling of fructose bisphosphate aldolase and variant surface glycoprotein was investigated. It was found that the large pool size of phosphate in trypanosomes precludes detailed kinetic analyses. Aldolase contains low levels of phosphoserine but the function of this phosphorylation has yet to be determined.

Animals↗
PubMed1989

Control of gastrointestinal motility by peptides: old peptides, new tricks--new peptides, old tricks.

The discovery of new peptides that may or may not be members of existing peptide families is stimulating research in the field of gastrointestinal motility. Before their function in control of human motility can be predicted, both anatomic and functional pathways must be determined in a number of animal models. In many instances this has just begun. In other instances old concepts must be revised. This review examines the recent findings that motor actions attributable to VIP and by extension to its colocalized family member PHI may occur by turning off a tonic release that has held the muscle in a relaxed state. For the opioid family, some of the very complex actions are probably attributable to its action to inhibit the tonic release of VIP. For the tachykinin/neurokinin family, the focus is on the potential role as a sensory transmitter released antidromically from afferent capsaicin-sensitive nerve endings. In summarizing the actions of galanin, the reader is cautioned against any extrapolation to other species, because the actions and structure of the peptides have been found to be different in each species examined. CGRP, again a sensory transmitter found colocalized with substance P, tends to exert an opposite action on the smooth muscle from substance P (that of relaxation), and the interactions between these peptides may well prove to be important in gastrointestinal reflexes. The PP, PYY, and NPY family require much more study in gastrointestinal motor systems but appear to act as presynaptic inhibitory transmitters in a variety of local motor reflexes. One caveat from one who studies these systems is never to predict the action of a new or old peptide in your system of study, because the complexity of the system appears to determine the action expressed.

Animals↗
PubMed1988

Single-channel recordings from cultured human retinal pigment epithelial cells.

We have applied patch-clamp techniques to on-cell and excised-membrane patches from human retinal pigment epithelial cells in tissue culture. Single-channel currents from at least four ion channel types were observed: three or more potassium-selective channels with single-channel slope conductances near 100, 45, and 25 pS as measured in on-cell patches with physiological saline in the pipette, and a relatively nonselective channel with subconductance states, which has a main-state conductance of approximately 300 pS at physiological ion concentrations. The permeability ratios, PK/PNa, measured in excised patches were 21 for the 100-pS channels, 3 for the 25-pS channels, and 0.8 for the 300-pS nonselective channel. The 45-pS channels appeared to be of at least two types, with PK/PNa's of approximately 41 for one type and 3 for the other. The potassium-selective channels were spontaneously active at all potentials examined. The average open time for these channels ranged from a few milliseconds to many tens of milliseconds. No consistent trend relating potassium-selective channel kinetics to membrane potential was apparent, which suggests that channel activity was not regulated by the membrane potential. In contrast to the potassium-selective channels, the activity of the nonselective channel was voltage dependent: the open probability of this channel declined to low values at large positive or negative membrane potentials and was maximal near zero. Single-channel conductances observed at several symmetrical KCl concentrations have been fitted with Michaelis-Menten curves in order to estimate maximum channel conductances and ion-binding constants for the different channel types. The channels we have recorded are probably responsible for the previously observed potassium permeability of the retinal pigment epithelium apical membrane.

Cells, Cultured↗
PubMed1988

In vivo inactivation of neurotensin in dog ileum: major involvement of endopeptidase 24-11.

The metabolism of tritiated neurotensin (NT) after close i.a. perfusion in ileal segments of anesthetized dog was studied. Venous effluents containing labeled metabolites and intact NT were collected and analyzed by high-performance liquid chromatography. The apparent half-life of the peptide was between 2 and 6 min. The tritiated metabolites of NT were identified as free tyrosine, NT-(1-7), NT-(1-8), NT-(1-10), NT-(11-13) and NT-(1-11). Pretreatment of dog ileum with thiorphan or captopril indicated that endopeptidase 24-11 inactivated NT by cleaving the peptide at the Pro10-Tyr11 and Tyr11-Ile12 bonds. Angiotensin-converting enzyme only participated in the secondary conversion of NT-(1-10) into NT-(1-8). The metabolisms of NT occurring in vivo and in vitro in central and peripheral organs are compared.

Animals↗
PubMed1987

Peptidases in dog-ileum circular and longitudinal smooth-muscle plasma membranes. Their relative contribution to the metabolism of neurotensin.

We established the content in neuropeptide-metabolizing peptidases present in highly purified plasma membranes prepared from the circular and longitudinal muscles of dog ileum. Activities were measured by the use of fluorigenic substrates and the identities of enzymes were confirmed by the use of specific peptidase inhibitors. Endopeptidase 24.11, angiotensin-converting enzyme, post-proline dipeptidyl aminopeptidase and aminopeptidases were found in both membrane preparations. Proline endopeptidase was only detected in circular smooth muscle plasma membranes while pyroglutamyl-peptide hydrolase was not observed in either tissue. The relative contribution of these peptidases to the inactivation of neurotensin was assessed. The enzymes involved in the primary inactivating cleavages occurring on the neurotensin molecule were as follows. In both membrane preparations, endopeptidase 24.11 was responsible for the formation of neurotensin-(1-11) and contributed to the formation of neurotensin-(1-10); a recently purified neurotensin-degrading neutral metallopeptidase was also involved in the formation of neurotensin-(1-10). A carboxypeptidase-like activity hydrolysed neurotensin at the Ile12-Leu13 peptide bond, leading to the formation of neurotensin-(1-12). Proline endopeptidase and endopeptidase 24.15 only occurred in circular muscle plasma membranes, yielding neurotensin-(1-7) and neurotensin-(1-8), respectively. In addition, the secondary processing of neurotensin degradation products was catalyzed by the following peptidases. In circular and longitudinal muscle membranes, angiotensin-converting enzyme converted neurotensin-(1-10) into neurotensin-(1-8) and tyrosine resulted from the rapid hydrolysis of neurotensin-(11-13) by bestatin-sensitive aminopeptidases. A post-proline dipeptidyl aminopeptidase activity converted neurotensin-(9-13) into neurotensin-(11-13) in circular muscle plasma membranes. The mechanism of neurotensin inactivation occurring in these membranes will be compared to that previously established for membranes from central origin.

Animals↗