PubMed Health⌕ Search

Biomedical subjects

D M Jones

Publications and source records attributed to D M Jones.

At least 19 recordsLinked to original sources
PubMed1995

Meningococcal infections in England and Wales: 1994.

One thousand one hundred and twenty-nine isolates of Neisseria meningitidis from cases of invasive disease were submitted to the PHLS Meningococcal Reference Unit in 1994, a fall of 13% from the total of 1297 in 1993. One hundred and seventy-four cases were diagnosed serologically, making 1303 laboratory ascertained cases, compared with 1368 in 1993. The overall fall of 4% was similar to the 5% fall in notifications to the Office of Population Censuses and Surveys. The seasonal increase between the third and fourth quarters of the year was less apparent than usual in 1994, when a higher proportion of cases occurred during the summer months. Regional rates of infection varied, notably in the proportions of group C infections, which were highest in the south east. DNA based typing techniques have clarified the characterisation of previously non-typable organisms. B4PI.4 has been identified as a recently emergent strain, which is now responsible for a quarter of all group B infections. Considerable regional variation was observed in the use of serodiagnosis. The monthly distribution of cases diagnosed serologically was similar to that of cases confirmed by isolation, but the age profile was skewed towards older patients.

Adolescent↗
PubMed1995

Control of group C meningococcal disease in Australian aboriginal children by mass rifampicin chemoprophylaxis and vaccination.

An outbreak of 12 cases of meningitis, 11 caused by Neisseria meningitidis serogroup C, occurred at Doomadgee from September, 1990, to April, 1991. The incidence of meningitis was 17.55/10(3) person-years. Only children aged 1-10 years were affected. In October, 1990, or shortly thereafter, 473/509 children aged between 1 and 15 years inclusive had one dose of Mencevax AC. From the time of vaccination until April, 1991, a further eight cases occurred, six in vaccinated children. Vaccine efficacy in 1-15 year olds was calculated as 77%. Despite this, in April, 1991, the prevalence of antibody to group C polysaccharide in vaccinated children (78%) was not significantly different from that in unvaccinated children and adults. 46 nonresponders were revaccinated, and, in February, 1992, 78% had antibodies to group C polysaccharide. In April, 1991, an estimated 3.0% of the population had group C organisms, carriage being directly related to household crowding. In June, 1991, 2 months after mass prophylaxis with rifampicin, none of these individuals were carriers. In October, 1991, the carriage rate of group C organisms was 0.64%. There have been no further cases caused by the epidemic strain. Although uncrowded housing is a basic need, mass chemoprophylaxis and two doses of vaccine for children should be used in similar outbreaks.

Adolescent↗
PubMed1995

Functional characteristics of the inner voice and the inner ear: single or double agency?

Double agency theories of short-term memory posit the functional independence of a phonological store (inner ear) and articulatory process (inner voice). A series of 5 experiments challenges this view. Articulatory suppression during retention of 9-item lists gives rise to a changing-state effect similar to that shown for irrelevant speech. Also, vocalized suppression is more disruptive than silently mouthed suppression, but this difference arises from vocalization itself rather than from any auditory feedback to which it gives rise. Class similarity between the to-be-remembered items and the articulatory material is not a critical determinant, but the effect occurs only with tests of serial order. For mouthed suppression, the irrelevant speech effect is only attenuated with changing-state suppression. Also, the presence of changing-state irrelevant speech abolishes the changing-state effect of articulatory suppression. Functional equivalence of codes from auditory, visual, and articulatory sources is claimed.

Adult↗
PubMed1995

Effects of endopeptidase 24.11 inhibition on plasma and tissue concentrations of vasoactive intestinal peptide.

1. In this study, we sought to determine the effect of endopeptidase 24.11 inhibition on the rate of metabolism of vasoactive intestinal peptide. The effect of such inhibition on the concentration of vasoactive intestinal peptide in two tissues was also investigated. 2. Male Sprague-Dawley rats were given the endopeptidase 24.11 blocker UK77,568 (10 mg/kg) or vehicle as a single intravenous injection or as a daily injection for 4 days. Two hours after the final or single injection, the rats were anaesthetized and blood was sampled to determine plasma concentrations of vasoactive intestinal peptide and angiotensin II. The hearts and kidneys were harvested and snap-frozen in liquid nitrogen. The plasma and tissue concentrations of vasoactive intestinal peptide and the plasma concentration of angiotensin II were determined by radioimmunoassay. In a separate group of experiments, male Sprague-Dawley rats were anaesthetized and carotid and jugular catheters were inserted. One hour after intravenous administration of UK77,568 or vehicle, an infusion of vasoactive intestinal peptide (10 pmol min-1 kg-1) was commenced via the jugular catheter. Blood was sampled to determine the vasoactive intestinal peptide concentration 1 h after commencing the vasoactive intestinal peptide infusion to calculate the metabolic clearance rate. 3. Plasma vasoactive intestinal peptide increased after acute (P < 0.05) but not chronic administration of UK77,568, while the concentration of vasoactive intestinal peptide in the heart increased after chronic administration (P < 0.0005). The concentration of vasoactive intestinal peptide in the kidney was unchanged after both acute and chronic endopeptidase 24.11 blockade. Plasma angiotensin II decreased significantly in the chronic group (P<0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1995

Priming the identification of environmental sounds.

Three experiments were conducted using a repetition priming paradigm: Auditory word or environmental sound stimuli were identified by subjects in a pre-test phase, which was followed by a perceptual identification task using either sounds or words in the test phase. Identification of an environmental sound was facilitated by prior presentation of the same sound, but not by prior presentation of a spoken label (Experiments 1 and 2). Similarly, spoken word identification was facilitated by previous presentation of the same word, but not when the word had been used to label an environmental sound (Experiment 1). A degree of abstraction was demonstrated in Experiment 3, which revealed a facilitation effect between similar sounds produced by the same type of source. These results are discussed in terms of the Transfer Appropriate Processing, activation, and systems approaches.

Adult↗
PubMed1995

Experimental infection of human nasal mucosal explants with Neisseria meningitidis.

The interaction of Neisseria meningitidis with rhinopharyngeal epithelium was studied by experimental infection of explants of human nasal turbinate mucosa with two wild strains: a fully capsulate case isolate, and an epidemiologically related non-capsulate nasopharyngeal isolate. After incubation for 4 h, epithelial cells of infected explants changed conformation from tall columnar morphology towards cuboidal, and there was increased discharge of mucus globules from goblet cells. By 24 h there was significant damage to infected epithelia, including projection of cells out of the surface, cytoplasmic blebbing and mitochondrial abnormalities. Meningococci were associated with surface non-ciliated cells by 4 h after infection. By 24 h after infection they were associated extensively with all cell types exhibiting damage. There was little association with secreted mucus. In areas of cell damage, penetration between surface cells was observed. Endocytosis into non-ciliated cells was observed in only a minority of explants studied and only in those infected for 24 h. From this intracellular site there was apparent migration to adjacent cells and to intercellular locations. No organisms were observed within or beneath basement membrane collagen in any explants but internalisation into mononuclear phagocytes was observed occasionally.

Cilia↗
PubMed1995

Serotypes and subtypes of Neisseria meningitidis: results of an international study comparing sensitivities and specificities of monoclonal antibodies.

An international study supported by the World Health Organization comparing monoclonal antibodies for serotyping and serosubtyping of Neisseria meningitidis strains was performed and the results were assessed in 1992. A collection of 6 serotype-specific (1, 2a, 2b, 4, 14, and 15) and 12 serosubtype-specific (P1.1, P1.2, P1.4, P1.5, P1.6, P1.7, P1.9, P1.10, P1.12, P1.14, P1.15, and P1.16) monoclonal antibodies was provided to 11 participating laboratories throughout the world. Monoclonal antibodies were tested on 85 Neisseria meningitidis strains with known reference results. Whole-cell enzyme-linked immunosorbent assay was used for analysis in 10 of 11 laboratories. The sensitivities and specificities of individual serotype- and subtype-specific monoclonal antibodies were evaluated. Differences in individual laboratories and with individual monoclonal antibodies were assessed. Relatively large differences in sensitivities were achieved in individual laboratories. On the contrary, the specificities remained at high levels in all laboratories. The sensitivities of serotype-specific monoclonal antibodies ranged from 72.0 to 100%. Individual serosubtype-specific monoclonal antibodies showed sensitivities ranging from 64.1 to 98.1%. The most frequent reason for the incorrect results obtained with the monoclonal antibodies were false-negative results. The collaborative study demonstrated that some monoclonal antibodies are not very sensitive. Another study to define the most suitable monoclonal antibodies is planned.

Antibodies, Bacterial↗
PubMed1995

Organizational factors in the effect of irrelevant speech: the role of spatial location and timing.

Typically, hearing a repeated syllable produces minimal disruption of serial recall of visual lists, but a sequence of different syllables impairs performance markedly. Two conditions for presenting an identical sequence of three syllables are compared: one, in which, by means of stereophony, each syllable is assigned to the left, center, or right auditory locus (three streams not changing in state), and another, in which the same syllable sequence occurs in one location only (one stream with changing state). Disruption was significantly less in the stereophonic than in the monophonic condition. There was a joint effect of changing state and location, not an effect of the number of locations alone. In Experiment 2, temporal predictability was used to manipulate changing state. The disruptive effect of regular presentation of a repeated syllable was markedly increased when it was presented irregularly. The results are discussed in the context of organizational factors in short-term memory.

Adult↗
PubMed1994

Meningococcal infections in England and Wales: 1993.

One thousand two hundred and ninety-seven meningococcal isolates of clinical significance were submitted for examination to the PHLS Meningococcal Reference Unit in 1993; almost the same total as in 1992. Changes in the number of isolates from individual regions ranged from falls of 25% to increases of 42%. The incidence of meningococcal disease rose late in 1993, apparently affected by the epidemic of influenza. The number of statutory notifications reported to the Office of Population Censuses and Surveys was--for the first time--markedly higher than the number of laboratory diagnosed cases. Serodiagnosis was used to confirm an increased number of clinically suspected cases in 1993.

Adolescent↗
PubMed1994

Accuracy of single concentration estimations of platelet angiotensin II receptor number. Its usefulness in screening for pregnancy-induced hypertension.

Platelet angiotensin II (AngII) receptor number has been suggested as a screening test for pregnancy-induced hypertension. However, markedly different false-positive rates have been reported, perhaps the result of differing methods used. We sought therefore to compare the two methods. Platelet AngII receptor number was determined by saturation analysis with computerized curve fitting and specific binding at a single radioligand concentration. The two methods were compared by correlation and by plotting their differences v their means, to determine their limits of agreement. There were significant correlations between the value obtained by saturation analysis and each of the three single ligand concentrations studied (1 nmol/L, P < .001; 500 pmol/L, P < .001; and 250 pmol/L, P < .01). However, for none of the three did the regression line approach the line of equality. Assessment of agreement by comparing differences and means for each subject showed increasing scatter with increasing receptor number and 95% confidence intervals too large to be clinically relevant. We conclude that the receptor number estimated from specific binding at one ligand concentration differs significantly from that obtained by saturation analysis. The limits of agreement of the two methods are wide and we urge caution in the use of single ligand concentration methods for estimating binding site densities.

Adult↗
PubMed1994

Effect of neutral endopeptidase on plasma and tissue concentrations of vaso-active intestinal peptide.

1. This study sought to determine if neutral endopeptidase metabolizes vaso-active intestinal peptide (VIP) and whether changes in the activity of this enzyme might explain the change in VIP metabolism which follows gastric sodium loading. The study also investigated whether prolonged inhibition of neutral endopeptidase was associated with inhibition of further secretion of VIP. 2. Male Sprague-Dawley rats were given the neutral endopeptidase inhibitor UK77,568 (10 mg/kg), or vehicle, tail vein injected, once or daily for 4 days. Two hours after injection the rats were anaesthetized, blood sampled to determine plasma concentrations of VIP and the hearts were harvested. Plasma and tissue concentrations of VIP were determined by radio-immunoassay. 3. Plasma VIP increased in response to UK77,568 at day 1 (P < 0.0005) but did not differ from control at day 4. The concentration of VIP in the heart did not increase at day 1 but had increased significantly at day 4 (P < 0.01). 4. It was concluded that neutral endopeptidase may metabolize VIP. Further, the increased concentration of VIP in the heart and the return of its plasma concentration to control levels at day 4 may be consistent with suppression of continued VIP secretion.

Animals↗
PubMed1994

Cleavage of human kininogen fragments at Met-Lys by human tissue kallikrein.

1. Tissue kallikrein (TK) cleaves low molecular weight kininogen (LK) at two sites to release kallidin: site I (between Arg389 and Ser390) is a typical cleavage point for a trypsin-like enzyme whereas site II (between Met379 and Lys380) is unusual and unique to TK. In order to learn more about the structural requirements and mechanism of cleavage at site II, we studied the hydrolysis by TK of several synthetic LK fragments varying in length between 4 and 22 residues and containing either site II only or both sites I and II. 2. Blocking site I cleavage in LK fragments by substituting DArg for LArg at position 389 or omitting site I from the sequence still allowed cleavage to proceed at site II. Replacement or deletion of selected amino acid residues in these fragments demonstrated that the presence of Arg381 was essential for site II cleavage to occur whereas Pro383, Phe385 and Ser386 could be replaced with Ala without affecting binding or cleavage by TK. Ki values towards TK were determined for all LK fragments in order to compare their binding affinities to the enzyme. Short peptides containing site II only exhibited high Ki values (> or = 100 microM) whereas longer fragments containing both sites I and II had Ki values of 2-7 microM. 3. In order to bring sites I and II into close proximity spatially and thus facilitating efficient cleavage in the enzyme-substrate complex, we prepared several cyclic analogs of the longer LK fragments.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Synthetic inhibitors of tissue kallikrein: effects in vivo in a model of allergic inflammation.

We have recently developed synthetic low molecular weight inhibitors of both tissue and plasma kallikreins. Several of these were evaluated in vivo in the ovalbumin-sensitised guinea pig for their ability to prevent the bronchoconstriction elicited by antigen challenge. The selective tissue kallikrein inhibitor CH-694 (but not the selective plasma kallikrein inhibitor CH-684) caused highly significant falls in airways resistance when it was administered at 10 mg/kg intraperitoneally 15 min before and 90 min after challenge. There was also a highly significant fall in the tissue kallikrein activity measured in broncho-alveolar lavage fluid. Inhibitors of tissue kallikrein may prove effective in the treatment of allergic inflammation in man.

Airway Resistance↗
PubMed1993

Meningococcal infections in England and Wales: 1992.

Fewer cases of meningococcal infection were identified in England and Wales during 1992 than in 1991. The 1301 isolates received by the PHLS Meningococcal Reference Unit represented a decrease of 7%, continuing the trend of the last two years. Most regions saw a reduction in cases, but increased numbers of isolates were received from some regions, notably Northern (up 22%), East Anglia (up 25%) and South West Thames (up 50%). Group C infections (down 17%) contributed disproportionately to the decrease; the numbers of isolates of this organism being the lowest since 1986. Serology is a reliable diagnostic method in cases where no isolate is obtained.

Adolescent↗
PubMed1993

Conversion of an immunogenic human immunodeficiency virus (HIV) envelope synthetic peptide to a tolerogen in chimpanzees by the fusogenic domain of HIV gp41 envelope protein.

The fusogenic (F) domain of human immunodeficiency virus (HIV) gp41 envelope (env) protein has sequence similarities to many virus and mediates the fusion of HIV-infected cells. During a survey of the immunogenicity of HIV env peptides in chimpanzees, we have observed that HIV peptide immunogenicity was dramatically altered by the NH2-terminal synthesis of the gp41 F domain to an otherwise immunogenic peptide. We compared two hybrid peptide types comprised of T helper (Th) and B cell epitopes of HIV gp120 env protein for their immunogenicity in chimpanzees. The Th-B epitope hybrid peptides contained the HIV gp120 Th cell determinant, T1 (amino acids [aa] 428-440)-synthesized NH2 terminal to gp120 V3 loop peptides, which contain B cell epitopes that induce anti-HIV-neutralizing antibodies (SP10IIIB [aa 303-321] and SP10IIIB [A] [aa 303-327]). The F-Th-B peptide contained the HIV gp41 F domain of HIVIIIB gp41 (aa 519-530)-synthesized NH2 terminal to the Th-B peptide. Whereas Th-B peptides were potent immunogens for chimpanzee antibody and T cell-proliferative responses, the F-Th-B peptide induced lower anti-HIV gp120 T and B cell responses. Moreover, immunization of chimpanzees with F-Th-B peptide but not Th-B peptides induced a significant decrease in peripheral blood T lymphocytes (mean decrease during immunization, 52%; p < 0.02). Chimpanzees previously immunized with F-Th-B peptide did not respond well to immunization with Th-B peptide with T or B cell responses to HIV peptides, demonstrating that the F-Th-B peptide induced immune hyporesponsiveness to Th and B HIV gp120 env determinants. These observations raise the hypothesis that the HIV gp41 env F domain may be a biologically active immunoregulatory peptide in vivo, and by an as yet uncharacterized mechanism, promotes primate immune system hyporesponsiveness to otherwise immunogenic peptides.

Amino Acid Sequence↗
PubMed1993

Demonstration of lipooligosaccharide immunotype and capsule as virulence factors for Neisseria meningitidis using an infant mouse intranasal infection model.

Using an infant mouse intranasal infection model, we have compared the virulence of 17 epidemiologically related isolates of Neisseria meningitidis associated with an outbreak of meningococcal disease in Gloucestershire, UK, and one German isolate. The isolates were all of serotype 15 subtype P1:7, 16 and were identical by restriction fragment length polymorphism analysis, but differed in either (i) whether they were isolated from a case or a carrier, (ii) the presence or absence of group B capsule, or (iii) their lipooligosaccharide (LOS) immunotype. The results indicate that capsule is a major virulence determinant and is required for colonization and hence for invasion. In addition, the LOS L3,7,9 immunotype, when compared to the L1,8,10 immunotype, is a secondary virulence factor which enhances colonization of nasal passages and invasion of the blood stream by both case and carrier isolates. Two case isolates which were unusual in possessing the L1,8,10 immunotype, established invasive infection, but this was associated with a switch to the L3,7,9 immunotype. The results confirm that LOS is a virulence factor for N. meningitidis and that immunotype L3,7,9 is associated with invasive disease.

Administration, Intranasal↗