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Biomedical subjects

S R Jones

Publications and source records attributed to S R Jones.

At least 19 recordsLinked to original sources
PubMed1997

Movement in the normal visual hemifield induces a percept in the 'blind' hemifield of a human hemianope.

We have investigated visual responses to moving stimuli presented to the normal hemifield of a hemianope, GY, who exhibits residual visual function in his right, 'blind' hemifield. Preliminary experiments established that his perception of moving stimuli localized in his 'blind' hemifield is retained when a similar stimulus is presented simultaneously in the normal hemifield. In response to a grating stimulus moving horizontally towards fixation in the non-foveal region of the normal, left hemifield, he perceives in addition to a normal motion percept in the left hemifield, a sensation of movement localized in the right hemifield. Qualitatively, this latter is indistinguishable from responses elicited by direct stimulation localized within his 'blind' hemifield by moving stimuli. We have investigated the characteristics of the mechanisms which induce the 'blind' field component of GY's responses to stimulation of the normal hemifield. We show that GY's sensitivity for detection of movement localized within his 'blind' hemifield is dependent on the direction of movement, the contrast and the velocity of a grating presented to the normal hemifield. No induced effects were recorded in response to colour or to non-moving, flickering stimuli. We examine the possible contribution of scattered light to our observations, and eliminate this factor by consideration of our experimental results. We discuss the neural mechanisms which may be involved in this response.

Humans↗
PubMed1997

In vitro infection of a cell line from Ictalurus nebulosus with Piscirickettsia salmonis.

Piscirickettsia salmonis, the etiologic agent of salmonid rickettsial septicemia (SRS), affects several species of salmonids. Previous reports using the appearance of cytopathic effect (CPE) as the criterion for susceptibility, showed that Piscirickettsia salmonis (ATCC strain) can be grown in vitro in some cells lines derived from salmonid fish, but not in BB cells from brown bullhead (Ictalurus nebulosus) and BF-2 cells from bluegill (Lepomis macrochirus). In this study we describe growth of P. salmonis (ATCC strain VR 1361) in a cell line previously believed to be nonpermissive for this organism. CPE was first detected in chinook salmon embryo (CHSE-214) and epithelioma papulosum ciprini (EPC) cell lines at 6 d postinfection (dpi). In contrast, using BB cell line, CPE was first detected 45 dpi and the monolayer completed CPE by 78 dpi. Electron microscopic examination of BB cells 78 dpi revealed free, intracytoplasmic and extracellular localization of the agent. P. salmonis was also observed within membrane-bounded vacuoles in BB cells, similar to that described in CHSE 214 cells. Contrary to earlier reports, results from the present study show that the BB cell line, is susceptible to Piscirickettsia salmonis infection. The delayed onset of CPE in BB cells in comparison to other permissive cell lines suggests that BB cells are not ideal hosts for P. salmonis. Interestingly, however, these results demonstrate that P. salmonis can infect non-salmonid cell lines, and raises the possibility that non-salmonid fish may play a role in the persistence and transmission of SRS in the natural environment.

Animals↗
PubMed1996

Expression of mRNA coding for the serotonin transporter in aged vs. young rat brain: differential effects of glucocorticoids.

Serotonin transporter mRNA expression in midbrain of young and aged rats was measured after long-term infusion of dexamethasone (0.01 and 0.05 mg/kg/day). Aging alone had no effect. Dexamethasone significantly decreased expression in both young and old rats but the effect was greater in the aged group. Adrenocortical dysregulation is common in elderly depression; our results suggest that glucocorticoids interact with aging to exacerbate abnormalities of serotonergic function, contributing to reduced antidepressant effectiveness.

Animals↗
PubMed1996

Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter.

Disruption of the mouse dopamine transporter gene results in spontaneous hyperlocomotion despite major adaptive changes, such as decreases in neurotransmitter and receptor levels. In homozygote mice, dopamine persists at least 100 times longer in the extracellular space, explaining the biochemical basis of the hyperdopaminergic phenotype and demonstrating the critical role of the transporter in regulating neurotransmission. The dopamine transporter is an obligatory target of cocaine and amphetamine, as these psychostimulants have no effect on locomotor activity or dopamine release and uptake in mice lacking the transporter.

Amphetamine↗
PubMed1996

Functional and anatomical evidence for different dopamine dynamics in the core and shell of the nucleus accumbens in slices of rat brain.

The characteristics of dopamine (DA) uptake and release were compared in the core and shell of the nucleus accumbens (NAc). DA release was elicited from rat brain slices by local electrical stimulation, and its extracellular concentration was monitored with fast-scan cyclic voltammetry using Nafion-coated, carbon-fiber microelectrodes. The voltammetric results show that the values of DA release and uptake in the shell NAc are approximately one-third of those measured in the core region, and DA uptake in the shell was less sensitive than the core to inhibition by either cocaine or nomifensine. The density of [3H]mazindol binding sites in the NAc was examined by autoradiography and the shell was found to have an average of half the number of DA uptake sites measured in the core region. This combination of anatomical and functional results shows that DA neurotransmission in the shell NAc is distinct from that in the core region. These data are consistent with the view that multiple functional forms of the DA transporter, exhibiting disparate kinetics and pharmacology, exist in different brain regions that exhibit disparate kinetics and pharmacology. Different forms of the transporter, combined with different release kinetics and auto- and heteroreceptor activity, give a vast range of possibilities for regional variation in DA neurotransmission.

Animals↗
PubMed1996

Effects of intermittent and continuous cocaine administration on dopamine release and uptake regulation in the striatum: in vitro voltammetric assessment.

Chronic daily injections of cocaine induce behavioral sensitization to subsequent cocaine challenge, while continuous infusion induces tolerance. Following a 7-day withdrawal period, we examined the effects of these two dosing regimens on: (1) baseline dopamine efflux and uptake following single-pulse electrical stimulation, (2) inhibition of uptake by cocaine; and (3) inhibition of efflux by autoreceptor activation. Cocaine (40 mg/kg per day) was administered to rats for 14 days either continuously by osmotic minipumps or intermittently by once-a-day injections. Minipumps containing saline were implanted in the control group. After 7 days of withdrawal, dopamine kinetics in the caudate was examined using in vitro fast-scan cyclic voltammetry. This technique provides very rapid measurements of dopamine in the extracellular space. Thus, when combined with endogenous dopamine efflux evoked by single-pulse, electrical stimulations, it was possible directly to measure the release and uptake components of the efflux. In the absence of pharmacological agents, no group differences were found in the amount of baseline dopamine released or in the uptake kinetics; the potency of bath-applied cocaine (0.03-60 microM) in inhibiting the uptake was also unaltered in either group. In contrast, the potency of quinpirole (an autoreceptor agonist, 5-250 nM) was significantly decreased and increased in the cocaine injection and pump groups, respectively. Thus, the cocaine administration regimen which produces sensitization results in a functional subsensitivity of release-modulating autoreceptors, while the tolerance-producing regimen results in autoreceptor supersensitivity.

Animals↗
PubMed1996

The synthesis and characterization of analogs of the antimicrobial compound squalamine: 6 beta-hydroxy-3-aminosterols synthesized from hyodeoxycholic acid.

Analogs of the aminosterol antimicrobial agent squalamine have been synthesized beginning from hyodeoxycholic acid. After carboxylic acid esterification and oxidation of both alcohol functions to ketones, the A/B ring junction was converted from cis to trans by acid-catalyzed isomerization. Different polyamines were added to the 3-keto group by reductive amination, yielding both the 3 alpha and 3 beta addition products. The synthetic products exhibited potent, broad-spectrum antimicrobial activity similar to that of the parent compound. Changing the identity of the polyamine or the stereochemistry of addition has little effect upon antimicrobial activity but appears to change the selectivity of the agents. The analogs are synthesized with high yield from inexpensive starting materials and are promising alternatives to squalamine as potential antibiotics.

Anti-Bacterial Agents↗
PubMed1996

Alpha-foetoprotein heterogeneity: what is its value in managing patients with germ cell tumours?

Alpha-foetoprotein (AFP) is widely used in the diagnosis, therapeutic monitoring and follow-up of patients with germ cell tumours. On occasion, the interpretation of a raised serum AFP measurement in a patient is confounded by the fact that AFP also increases in a variety of liver and gastrointestinal diseases. AFP exists as a number of isoforms, which can be separated by their differential binding to plant lectins. Thus, AFP-concanavalin A (ConA) binding affords a means of distinguishing between a raised AFP of teratoma or liver aetiology and has recently been reported to possess sensitivity and specificity approaching 100%. We present a patient in whom column chromatographic ConA binding was used as a basis for clinical management decisions for treatment for relapsed germ cell testicular tumour. The presumption of high test specificity led to a delay in the diagnosis of cancer recurrence, from which the patient ultimately died. We conclude that the clinical utility of lectin binding assays currently remains uncertain and further evaluation is warranted.

Adult↗
PubMed1996

Effects of immersion in water on survival of preimaginal stages of Haematobia irritans (Diptera: Muscidae).

Laboratory studies on effects of immersion and immersion duration on all Haematobia irritans (L.) preimaginal stages revealed a significant disparity in tolerance limits among different developmental stages and in tolerance to different immersion durations (0, 1, 6, 18, and 30 h). Of the 4 preimaginal stages, 2nd instars were most susceptible to immersion of any duration, whereas eggs and pupae were most resistant. All instars were intolerant of immersion durations >6 h, with <10% survival at 6-, 18-, and 30-h immersion durations. Survival of 2nd instars was reduced to 38% by 0-h immersion, when compared with the control group. Adult eclosion was reduced by immersion durations of 18 and 30 h during the pupal stage. Life stage survival was dependent upon immersion duration, with survival generally decreasing as a negative linear function of increasing immersion duration. Immersion durations of 0, 1, 6, 18, and 30 h resulted in overall mortality rates of approximately 30, 37, 53, 61, and 82%, respectively. In wet regions with low elevations, water accumulation may significantly affect horn fly distribution and abundance. In drier regions, where flooding events are sporadic and water accumulation variable, the effect on horn fly populations is uncertain.

Animals↗
PubMed1995

Epstein-Barr virus isolates with the major HLA B35.01-restricted cytotoxic T lymphocyte epitope are prevalent in a highly B35.01-positive African population.

An influence of cytotoxic T lymphocyte (CTL) response over Epstein-Barr virus (EBV) evolution was first suggested by the finding that virus isolates from highly HLA-A11-positive Oriental populations were specifically mutated in two immunodominant A11-restricted CTL epitopes. Here we turn to a second HLA allele, B35.01 and show that B35.01-restricted CTL responses in Caucasian donors reproducibly map to a single peptide epitope, YPLHEQHGM, representing residues 458-466 of the type 1 EBV nuclear antigen 3A protein (B95.8 strain). In this case, however, most EBV isolates from a highly B35.01-positive population (in The Gambia) either retained the CTL epitope sequence or carried a mutation (P-->S at position 2) which conserved antigenicity; changes leading to reduced antigenicity (Y-->N at position 1) were found in only a minority of cases. Furthermore, CTL recognizing the YPLHEQHGM epitope could be reactivated from the blood of some B35.01-positive Gambian donors by in vitro stimulation with the synthetic peptide, indicating that epitope-specific immunity does exist in this population. Possible differences between the A11-based and B35.01-based studies are discussed.

Amino Acid Sequence↗
PubMed1995

Comparison of dopamine uptake in the basolateral amygdaloid nucleus, caudate-putamen, and nucleus accumbens of the rat.

Regional differences in the kinetics and pharmacological inhibition of dopamine uptake were investigated with fast-scan cyclic voltammetry in both the intact rat brain and a brain slice preparation. The regions compared were the basolateral amygdaloid nucleus, caudate-putamen, and nucleus accumbens. The frequency dependence of dopamine efflux evoked in vivo by electrical stimulation of the medial forebrain bundle was evaluated by nonlinear curve fitting with a Michaelis-Menten-based kinetic model. The Km for dopamine uptake was found to be significantly higher in the basolateral amygdala (0.6 microM) than in the other two regions (0.2 microM), whereas the Vmax value for dopamine uptake in the basolateral amygdala was significantly lower (0.49 microM/s vs. 3.8 and 2.4 microM/s in the caudate and accumbens, respectively). Similar kinetics were also obtained in brain slices. Addition of a dopamine uptake inhibitor, cocaine or nomifensine (10 microM), to the perfusion buffer increased the apparent Km value > 25-fold in slices of both the caudate-putamen and nucleus accumbens. In contrast, neither uptake inhibitor had an observable effect in the basolateral amygdaloid nucleus. Thus, dopamine uptake in the rat brain is regionally distinct with regard to rate, affinity, and sensitivity to competitive inhibition.

Amygdala↗
PubMed1995

Fetal mortality associated with cholestasis of pregnancy and the potential benefit of therapy with ursodeoxycholic acid.

Cholestasis of pregnancy is associated with increased fetal morbidity and mortality and should be treated actively. The significance attached to pruritus in pregnancy is often minimal, but it is a cardinal symptom of cholestasis of pregnancy, which may have no other clinical features. Eight women with previous cholestasis of pregnancy were referred to The Liver Unit within a 12 month period for advice concerning future pregnancies. Thirteen pregnancies had been affected by cholestasis of pregnancy and 12 had been treated expectantly with resultant perinatal morbidity or mortality in 11 (one normal delivery), including; eight stillbirths, two premature deliveries with fetal distress (one died in perinatal period), and an emergency caesarean section for fetal distress. The other pregnancy was treated actively and delivery was uncomplicated. Subsequently, three of these cases with recurrent cholestasis of pregnancy were referred while pregnant. In each, cholestasis developed with severe pruritus, gross increase of serum bile acids, and deranged liver tests. Each was treated with the choleretic agent ursodeoxycholic acid, with rapid clinical improvement and resolution of deranged biochemistry. In conclusion, cholestasis of pregnancy continues to be treated expectantly despite its association with increased morbidity and mortality and evidence suggesting improved prognosis with active treatment and the potential of reducing the associated perinatal mortality. In an uncontrolled series of three patients with cholestasis of pregnancy, ursodeoxycholic acid seemed to provide safe and effective therapy.

Adult↗
PubMed1995

Screening for Down's syndrome: the first two years experience in Bristol.

OBJECTIVES: To evaluate the effectiveness of a programme for antenatal screening for Down's syndrome using alpha fetoprotein and total human chorionic gonadotrophin as maternal serum markers. SETTING: A district general hospital providing a screening service to a local purchasing authority and (under contract) to another purchasing authority in the same region. METHODS: Patients were counselled and screened between 15 and 20 weeks gestation and Down's risk estimates calculated using the maternal serum marker results as modifiers of the age related risk. Outcome was determined in collaboration with the Regional Cytogenetics Unit. OUTCOME MEASURES: Detection rate for Down's syndrome, false positive rate, uptake of screening, and uptake of amniocentesis. RESULTS: In two years 22816 women were screened (approximately 84% of population); 32 Down's pregnancies were identified, 19 (59.4%) had a reported risk of > or = 1:250 and 20 (62.5%) a reported risk of > or = 1:300. Of those screened before 17 weeks, 16/20 (80%) had a reported risk of > or = 1: 300 compared with 4/12 (33%) of those screened later (P = 0.008); 4.64% of patients screened had reported risks > or = 1: 250 and 5.87% reported risks of > or = 1:300. Amniocentesis uptake was 70% in patients with reported risks of > or = 1:300. CONCLUSIONS: Overall the screening programme was effective but screening before 17 weeks was very much more effective than screening later.

Adolescent↗
PubMed1995

Dopamine supersensitivity and hormonal status in puerperal psychosis.

BACKGROUND: We examine the dopamine receptor supersensitivity hypothesis of puerperal psychosis, and explore puerperal changes in the functional sensitivity of this receptor system. METHOD: Dopamine receptor sensitivity was estimated using growth hormone (GH) response to apomorphine challenge following delivery in 37 control women, and 11 deliveries in 10 women at 'high risk' of puerperal psychosis (previous history of puerperal affective or non-puerperal manic psychosis). Tests were on days 4 or 5, 11 or 12 and at six weeks postpartum. RESULTS: Three women developing puerperal psychosis had subsensitive GH responsiveness on day 4. GH response to 67 challenge tests (in control and 'high risk' women) increased between days 4 or 5 and six weeks postpartum (P < 0.05). GH response at six weeks correlated with free thyroxine levels (P < 0.01). CONCLUSIONS: These three cases do not support the stated hypothesis. Hypothalamic dopamine receptor sensitivity increases during the puerperium; thyroxine might influence this.

Adult↗