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Biomedical subjects

B J Jones

Publications and source records attributed to B J Jones.

At least 37 records · Page 2Linked to original sources
PubMed1996

Treatment of neutropenic oral ulceration in human immunodeficiency virus infection with G-CSF.

We report the novel use of granulocyte colony-stimulating factor in the treatment of severe oral ulceration in human immunodeficiency virus-associated neutropenia. A 38-year-old man with acquired immunodeficiency syndrome developed severe refractory oral aphthous ulceration that persisted for 6 months despite a range of empirical treatments including corticosteroid. Rapid resolution of the ulceration occurred once the neutrophil count was restored to normal with granulocyte colony-stimulating factor.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Functional characterization of the 5-HT terminal autoreceptor in the guinea-pig brain cortex.

1 In guinea-pig cerebral cortical slices in vitro we have shown that the rank order of potency of 5-hydroxytrptamine (5-HT), 5-carboxamidotryptamine and sumatriptan for inhibition of electrically stimulated [3H]-5-HT release correlates well with published data on their 5-HT1D receptor binding affinities. 2 Both the non-selective 5-HT1D receptor antagonist, methiothepin and the selective 5-HT1D receptor antagonist, N-[4-methoxy-3-(4-methyl-1-piperazinyl]phenyl]-2'-methyl-4'- (5-methyl-1,2,4-oxadiazole-3-yl) [1,1-biphenyl]4-carboxamide (GR127935) increased stimulated [3H]-5-HT release per se and also attenuated agonist-induced inhibition of [3H]-5-HT release. GR127935 (10 nM-100 nM) produced a pA2 of 9.0 against 5-HT, which is consistent with its 5-HT1D receptor binding affinity. 3 From these findings we conclude that, in guinea-pig cerebral cortex, the 5-HT terminal autoreceptor is of the 5-HT1D receptor subtype. However, three observations suggest the presence of multiple terminal autoreceptors: shallow inhibition curves to the agonists; a shallow Schild slope of GR127935 antagonism and differences in the maximal responses to 5-HT between whole cortex and frontal cortex.

Animals↗
PubMed1994

A high resolution study of the glycocalyx of rat uterine epithelial cells during early pregnancy with the field emission gun scanning electron microscope.

The field emission gun scanning electron microscope has been used to investigate morphological changes at the macromolecular level in the glycocalyx of rat uterine luminal epithelial cells during early pregnancy. This very high resolution microscope has allowed visualisation at a level previously unobtainable and has enabled us to establish that dramatic alterations occur in this glycocalyx at the time of blastocyst attachment. On d 1 of pregnancy a prominent, filamentous glycocalyx radiates from the microvilli. However, by d 6 of pregnancy when the microvilli have been replaced by irregular cell surface protrusions, the glycocalyceal filaments are completely lost and the plasma membrane appears smooth and covered with a felt-like coating. These morphological observations suggest a major reorganisation in surface carbohydrates during early pregnancy and extend histochemical observations on the uterine epithelial glycocalyx.

Animals↗
PubMed1993

Enrichment for metallothionein does not confer resistance to cisplatin in transfected NIH/3T3 cells.

Evidence has been presented both that metallothionein does and does not produce resistance to cisplatin. The metallothionein-enriched cells described in most previous studies have been selected for resistance to heavy metals, such as cadmium, or have been maintained in a medium enriched for the metals. Exposure to toxic metals could alter the cells in many ways. This report addresses the effect of metallothionein content alone, independent of exposure to metals, on cellular resistance to cisplatin. The toxicity of cisplatin was compared in NIH/3T3 cells that vary in their content of metallothionein as a consequence of transfection with a plasmid that results in the constitutive expression of metallothionein. The plasmid contains the bovine papillomavirus genome and the mouse metallothionein-I gene; it is driven by a glucose-regulated protein of 78 kD. Control cells were transfected with a similar plasmid in which the coding sequences for metallothionein were inverted and separated from the promoter, thereby abolishing expression. Expression of metallothionein required neither selection nor maintenance of cells in the presence of heavy metals. Despite large differences between the two types of cells in their cellular content of metallothionein and in their resistance to the toxicity of cadmium, no differences in resistance to cisplatin were observed.

3T3 Cells↗
PubMed1993

Distribution of gallium-67 in normal and hypotransferrinemic tumor-bearing mice.

The mechanism by which 67Ga accumulates in tumors is controversial. The most popular theory is that 67Ga binds to transferrin and gains access to cells by the transferrin receptor. However, substantial evidence suggests that uptake of 67Ga may not be universally mediated by transferrin in tumors. To determine whether transferrin is required for uptake of 67Ga in vivo, we compared the uptake of 67Ga by two types of implanted tumors and by normal tissues in normal and severely hypotransferrinemic strains of Balb/C mice. One type of tumor was strongly gallium-avid in normal mice; the other was not. Uptake of 67Ga by normal soft tissues was markedly less in hypotransferrinemic than in normal mice. Uptake of 67Ga by bone was equivalent in the two types of mice. For the more gallium-avid tumor, uptake of 67Ga was similar and the ratio of tumor-to-background activity was substantially higher in the hypotransferrinemic than in the normal mice. For the less gallium-avid tumor, uptake was significantly less in hypotransferrinemic than in normal mice. These data suggest that uptake of 67Ga by bone and by some tumors may be a transferrin-independent process.

Animals↗
PubMed1992

Uptake of cadmium is diminished in transfected mouse NIH/3T3 cells enriched for metallothionein.

To determine the relationship between cellular uptake of cadmium and content of metallothionein, we measured uptake of 109Cd in cells that differed in content of metallothionein (MT). MT cells were derived from NIH/3T3 cells by transfection with a plasmid containing the genome of bovine papilloma virus and the mouse metallothionein-I gene, driven by the promotor for the glucose-regulated protein of 78 kDa. Control cells were similarly transfected with bovine papilloma virus-based plasmids with the gene for metallothionein inverted and thus separated from the promoter (TM), or deleted, along with the promoter (BPA). The number of copies of bovine papilloma virus-based plasmids was similar in MT, TM, and BPA cells, approximately 100 per cell. MT cells were more than 10 times more resistant to the lethal effect of cadmium than were the control cells. Synthesis of metallothionein was 15-fold greater in the MT cells than in the TM or BPA cells. The uptake of 109Cd by the cells enriched in metallothionein was 4-fold less than by the control cells. These data suggest that an increased content of metallothionein may protect some cells from the toxic effects of cadmium, in part, by diminishing uptake of the metal.

3T3 Cells↗
PubMed1992

Effect of 5-HT1A receptor agonists in two models of anxiety after dorsal raphe injection.

The purpose of the present study was two-fold. Firstly, to present a more comprehensive analysis of the disinhibitory effects of 5-HT1A receptor agonists after discrete dorsal raphe (DRN) injections (Higgins et al. 1988). Secondly, the effects of the 5-HT1B receptor agonist CGS12066B and the 5-HT1B/1C agonist mCPP were examined following injection into this nucleus. The increases in social interaction (SI) induced by intra-raphe injections of 8-OH DPAT (0.02-1 micrograms), buspirone (0.04-0.2 microgram), ipsapirone (0.2 microgram) and gepirone (0.2-1 micrograms) under a high light unfamiliar paradigm (HLU) were typically due to increased bout frequency, duration and a higher incidence of sniff, follow, allogroom behaviour. These increases were qualitatively similar to those seen in control animals tested under low light/familiar (LLF) conditions, thus supporting the belief that the drug-induced increases in SI reflected decreases in anxiety. Furthermore, at doses effective under the HLU condition, 8-OH DPAT, buspirone and gepirone failed to modify SI under conditions of minimal suppression (LLF paradigm). At doses which significantly increased punished responding in a water-lick conflict test 8-OH DPAT, ipsapirone and gepirone tended to also increase unpunished rates of drinking. However, in drug untreated rats, prior habituation to the test apparatus also increased unpunished drinking, suggesting some neophobia-induced suppression. At a comparatively high dose, the 5-HT1B agonist CGS12066B (2.5 micrograms), but not the putative 5-HT1B/1C agonist mCPP (0.5-12.5 micrograms), increased SI under the HLU condition.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Effect of high-energy shock wave frequency on viability of malignant cell lines in vitro.

In this study, the effects of high-energy shock wave (HESW) frequency on the viability of three different malignant cell lines were evaluated using a piezo-electric generator. The cell lines studied were AR42-J, VX-2 and HeLa. These cells were targeted both in free suspension and immobilised in gelatine beads. All cell lines in free suspension were acutely sensitive to HESW over a range of frequencies. When cells were immobilised in gelatine, however, the effect on cell viability was not as pronounced. However, at frequencies of 80- and 160-Hz kill rates approaching 80 and 90%, respectively, were observed. Cell proliferation following HESW treatment was not adversely affected. This study demonstrates that single cell suspensions are not appropriate for assessing the in vitro cellular effects of HESW. However, even when cells were immobilised in gelatine, high-frequency HESW produced substantial kill rates. The effects of high-frequency HESW merit further evaluation particularly using in vivo tumour.

Animals↗
PubMed1991

Evidence that the amygdala is involved in the disinhibitory effects of 5-HT3 receptor antagonists.

The effects of various 5-HT3 receptor antagonists were examined in the social interaction (SI) test following discrete microinjection into either the dorsal raphe nucleus (DRN) or amygdala of the rat. Following DRN injection, ondansetron, ICS205-930, and MDL72222 (5-500 ng) all failed to modify SI under high light/unfamiliar (HLU) test conditions relative to vehicle pretreated controls. The 5-HT3 receptor agonist, 2-Me 5-HT (100-2500 ng), was similarly ineffective under both HLU and low light/familiar (LLF) conditions, although 5-HT (20-100 ng) increased SI under the HLU paradigm. After amygdaloid injection, ondansetron (10-100 ng), granisetron (1-10 ng), ICS205-930 (10-100 ng), GR 65630 (1-10 ng), and MDL72222 (100-1000 ng) all significantly increased SI under the HLU but not LLF condition. Furthermore, a detailed behavioural analysis revealed that the behaviours underlying this increase were similar to those seen in vehicle pretreated animals tested in the LLF compared to HLU condition. The benzodiazepine, flurazepam (200 ng), increased both SI (HLU condition) and punished responding in a modified water-lick conflict model, after amygdaloid injection. Both ondansetron (10-1000 ng) and ICS205-930 (1-100 ng) were ineffective in the conflict test. Finally, 2-Me 5-HT and 5-HT (100-10,000 ng) reduced SI under the LLF test condition with no concomitant change in locomotor activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗
PubMed1991

Acute and chronic bioeffects of single and multiple doses of piezoelectric shockwaves (EDAP LT.01).

Piezoelectric second generation lithotriptors are an established means of administering extracorporeal shockwave lithotripsy (ESWL) enabling treatment to be performed without anaesthesia or analgesia, but higher shockwave doses and multiple or staged treatment are frequently required. The bioeffects of this modality of ESWL, therefore, require further assessment. Seven experimental groups of adult male rabbits were treated using the EDAP LT.01 in order to determine the acute and chronic bioeffects of clinical dose, excess dose, divided excess dose, high frequency and multiple treatment (X10) piezoelectric shockwaves (PSW). Renal function was measured before and after treatment using mercaptoacetyltriglycine (MAG 3) scans. Gross and histological morphological changes were assessed at one and 30 days following application of PSW. Application of single clinical dose PSW was not associated with any significant functional or morphological renal injury. Excess dose PSW caused transient gross renal contusion, which resolved in the majority of animals with no persistent microscopic abnormality. Divided excess dose PSW resulted in no gross or microscopic damage. High frequency PSW was associated with mild histological abnormality. Multiple PSW treatments caused small discrete fibrotic lesions in all cases, without any change in renal function.

Animals↗
PubMed1991

The pharmacology of fluparoxan: a selective alpha 2-adrenoceptor antagonist.

1. This paper describes the pharmacology of the novel alpha 2-adrenoceptor antagonist fluparoxan (GR 50360) which is currently being studied clinically as a potential anti-depressant. Idazoxan and yohimbine were included in many studies for comparison. 2. In the rat isolated, field-stimulated vas deferens and the guinea-pig isolated, field-stimulated ileum preparations, fluparoxan was a reversible competitive antagonist of the inhibitory responses to the alpha 2-adrenoceptor agonist UK-14304 with pKB values of 7.87 and 7.89 respectively. In the rat isolated anococcygeus muscle, fluparoxan was a much weaker competitive antagonist of the contractile response to the alpha 1-adrenoceptor agonist phenylephrine with a pKB of 4.45 giving an alpha 2: alpha 1-adrenoceptor selectivity ratio of greater than 2500. 3. In the conscious mouse, fluparoxan (0.2-3.0 mg kg-1) was effective by the oral route and of similar potency to idazoxan in preventing clonidine-induced hypothermia and antinociception. In the rat, UK-14304-induced hypothermia (ED50 = 1.4 mg kg-1, p.o. or 0.5 mg kg-1, i.v.) and rotarod impairment (ED50 = 1.1 mg kg-1 p.o. or 1.3 mg kg-1, i.v.) were antagonized by fluparoxan. Fluparoxan, 0.67-6 mg kg-1, p.o., also prevented UK-14304-induced sedation and bradycardia in the dog. 4. In specificity studies fluparoxan had low or no affinity for a wide range of neurotransmitter receptor sites at concentrations up to at least 1 x 10(-5) M. It displayed weak affinity for 5-HT1A (pIC50 = 5.9) and 5-HT1B (pKi = 5.5) binding sites in rat brain. 5. We conclude that fluparoxan is a highly selective and potent alpha 2-adrenoceptor antagonist. The density of rat brain [3H]-dihydroalprenolol binding sites was reduced by 26% when fluparoxan was administered chronically for 6 days at a dose of 12 mg kg- 1 orally twice daily. The down-regulation of beta-adrenoceptors by fluparoxan is consistent with its antidepressant potential.

Adrenergic alpha-Agonists↗
PubMed1991

Continued clinical validation of dementia diagnosed in the community using the Cambridge Mental Disorders of the Elderly Examination.

We describe the outcome 2 years later of elderly Cambridge residents who had been diagnosed as demented using the Cambridge Mental Disorders of the Elderly Examination. Mortality rates were high but diagnoses were confirmed for all of the 43 moderate and severe cases who survived for this period, and for 51 of the 56 subjects who had been rated initially as mildly demented; 28 of the 56 mildly demented subjects progressed to more severe levels of impairment. As many as 12 of the 24 original minimally demented cases showed evidence of intellectual deterioration, which lends weight to the validity of this experimental category.

Aged↗
PubMed1991

Influence of prior orchiopexy on stage and prognosis of testicular cancer.

Thirty-four cryptorchid testis cancer cases were studied, of whom 9 patients had prior orchiopexy at the time of cancer diagnosis. Disease stage in this group was: stage I = 4, stage II = 1 and stages III and IV = 4 cases. Seventy-eight percent of these cases (n = 7) had non-seminomas; 4 of these patients died. In the uncorrected cryptorchidism group (n = 25), disease stage was: stage I = 12, stage II = 9 and stages III and IV = 4 cases. Of these cases, 64% (n = 16) had seminomas and 6 patients died. Orchiopexy marginally reduced the symptomatic interval for subsequent cancer and probably decreased the risk of seminoma development. Orchiopexy did not lead to a more favourable disease presentation or prognosis because of the adverse bias of advanced-stage non-seminomas in this group.

Adult↗
PubMed1990

A national survey of mental health professionals concerning the causes of early infantile autism.

This study is an analysis of mental health professionals' (N = 221) attitudes with regard to the etiology of infantile autism. A random sample of members of the American Psychiatric Association reveals a strong endorsement of a biogenic perspective. Attitudes are analyzed further with regard to variation by school of thought and number of years treating autistic patients.

Attitude of Health Personnel↗
PubMed1990

[3H] GR67330, a very high affinity ligand for 5-HT3 receptors.

GR67330 potently inhibited 5-hydroxytryptamine (5-HT)-induced depolarizations of the rat isolated vagus nerve. At the higher concentrations used (0.3 nmol/l-1 nmol/l) this was accompanied by a marked reduction in the maximum response to 5-HT. The calculated pKB value was 10.2. The binding of the tritiated derivative of GR67330 to homogenates of rat entorhinal cortex was examined. Kinetic analysis revealed that specific [3H] GR67330 (0.1 nmol/l) binding was rapid and reversible. Association and dissociation rate constants were 1.48 +/- 0.36 x 10(8) mol/l-1 s-1 and 7.85 +/- 0.41 x 10(-3) s-1 respectively. Equilibrium saturation analysis revealed specific binding was to a single site (Bmax 22.6 +/- 0.21 fmol/mg protein) of high affinity (Kd 0.038 +/- 0.003 nmol/l). At low ligand concentrations, specific binding was up to 90% of total binding. If unlabelled GR67330 was used to define non-specific binding two sites were evident (Kd1 0.066 +/- 0.007 nmol/l, Kd2 20.1 +/- 9.7 nmol/l; Bmax1 31.5 +/- 3.2 fmol/mg protein, Bmax2 1110 +/- 420 fmol/mg protein). [3H] GR67330 binding was inhibited potently by 5-HT3 antagonists and agonists. Ligands for other 5-HT receptors and other neurotransmitter receptors were either only weakly active or inactive at inhibiting binding. Hill numbers for antagonist inhibition of binding were close to unity, except for quipazine which was significantly greater than one. In common with other 5-HT3 binding studies, all 5-H-agonist tested had Hill numbers greater than one (1.51-1.71). GR38032 and GR65630 inhibited a greater proportion of binding than other 5-HT3 antagonists, this additional binding was interpreted as inhibition from a second saturable site unrelated to the 5-HT3 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗