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Biomedical subjects

D M Jones

Publications and source records attributed to D M Jones.

At least 127 records · Page 7Linked to original sources

Recovery of viable but non-culturable Campylobacter jejuni.

Suspensions of Campylobacter jejuni became non-culturable after storage in sterilized pond water at 4 degrees C for periods between 18 and 28 d, depending on the strain. Suspensions of four strains of C. jejuni that had been in water for 6 weeks, and shown to be non-culturable, were fed to suckling mice. Colonization of mice was established with two of the strains and failed with the other two strains. Examination of these suspensions under the electron microscope showed some cocci having the appearance of being viable, but most cocci and all remaining spiral forms showed extensive degeneration. The results indicate that non-culturable coccal forms of C. jejuni are capable of infecting mice but that this property may differ between strains.

Administration, Oral↗

An epidemiologically valuable typing method for Neisseria meningitidis by analysis of restriction fragment length polymorphisms.

A restriction fragment length polymorphism (RFLP) typing method was developed for Neisseria meningitidis. A cloned EcoRI fragment from a Neisseria meningitidis Group B serotype 15P1.16 sulphonamide-resistant strain was used to probe Southern blots of total chromosomal DNA restriction fragments (enzyme AvaI). A group of 75 apparently unrelated organisms gave rise to 26 different restriction fragment length patterns and two different groups of epidemiologically related strains had RFLP patterns that were distinct for each group. The technique was highly reproducible and discriminatory. The RFLP data were compared with the results of serotyping and subtyping and isoenzyme electrophoretotyping. The RFLP data were consistent with those from the alternative typing methods; clones defined by isoenzyme analysis were subdivided by this technique. The use of RFLP typing by cloned probes should be of considerable epidemiological value.

Blotting, Southern↗

Penicillin-resistant isolates of Neisseria lactamica produce altered forms of penicillin-binding protein 2 that arose by interspecies horizontal gene transfer.

Isolates of Neisseria lactamica that have increased resistance to penicillin have emerged in recent years. Resistance to penicillin was shown to be due to the production of altered forms of penicillin-binding protein 2 (PBP 2) that have reduced affinity for the antibiotic. The sequences of the PBP 2 genes (penA) from two penicillin-resistant isolates were almost identical (less than or equal to 1% sequence divergence) to that of a penicillin-susceptible isolate, except in a 175-bp region where the resistant and susceptible isolates differed by 27%. The nucleotide sequences of these divergent regions were identical (or almost identical) to the sequence of the corresponding region of the penA gene of N. flavescens NCTC 8263. Altered forms of PBP 2 with decreased affinity for penicillin in the two penicillin-resistant isolates of N. lactamica appear, therefore, to have arisen by the replacement of part of the N. lactamica penA gene with the corresponding region from the penA gene of N. flavescens.

Amino Acid Sequence↗

Some physiological and pharmacological factors affecting uterine motility as measured by electromyography in the mare.

Two intact and 2 ovariectomized mares aged 3-16 years had bipolar electrodes implanted in the myometrium to measure electromyographic (emg) activity during normal and exogenously simulated (with oestrogen and progesterone) cyclical activity (anoestrus, transition, oestrus and dioestrus). Oxytocin, cloprostenol, propantheline bromide and clenbuterol were administered during each cycle stage. In 1 mare, emg activity was recorded during natural breeding (4 times) and through the first 20 days of pregnancy. Simultaneous intrauterine pressure recordings (IUP) using an open tipped catheter system were taken occasionally. For mares in oestrus, we recorded short bursts of high amplitude emg activity separated by quiet periods, a pattern that is indicative of uterine contractions. During dioestrus the duration of emg activity increased, but amplitude decreased and interspersed quiet periods were less well defined, indicative of uterine tonus. The emg patterns seen in anoestrus and transition were intermediate. At breeding there was a short-lived increase in emg activity, unlikely to be caused by endogenous hormone release. During early pregnancy the emg characteristics varied depending on whether the fertilized ovum was in the oviduct, migratory or fixed, with emg activity increasing to 100% after Day 16 when uterine tone is maximal. Oxytocin and cloprostenol caused prolonged emg activity followed initially by a short burst pattern that was most pronounced in oestrus and least in dioestrus and suggests uterine motility is stimulated to a greater extent during oestrus. Propantheline decreased emg activity, whereas cloprostenol caused minimal changes. IUP increased with uterine stimulants and decreased with uterine relaxants, but showed little variation between cyclic states. There was little correlation, statistically or visually, between IUP and emg activity during the oestrous cycle with or without drug treatment. Because emg analysis gave consistent results and demonstrated significant differences between oestrus and dioestrus that neither agreed nor correlated with IUP, the validity of the IUP recording technique used in this study (as well as those used in general for the mare) is questioned. It is suggested that extrauterine factors such as intestinal motility and intra-abdominal pressure changes could influence IUP responses.

Animals↗

A surface polysaccharide forms when gonococci are converted to serum resistance by cytidine 5'-monophospho-N-acetyl neuraminic acid.

A serum-susceptible, guinea-pig chamber-passaged, laboratory strain (BS4 (agar)) of Neisseria gonorrhoeae was converted to serum resistance by incubation with cytidine 5-monophospho-N-acetyl neuraminic acid (CMP-NANA) and examined by electron microscopy after staining with ruthenium-red. In contrast to serum susceptible gonococci incubated without CMP-NANA, the majority (60-70%) of the serum resistant organisms showed a surface accumulation of polysaccharide. This surface polysaccharide was enhanced on all the resistant gonococci after incubation with fresh human serum. Control susceptible gonococci were devoid of the polysaccharide after incubation with heated human serum. Identical results were obtained with a fresh gonococcal isolate which had lost serum resistance on subculture but which, in common with 3 other isolates, was restored to serum resistance by incubation with CMP-NANA.

Animals↗

Group A meningococcal disease in England associated with the Haj.

An outbreak of group A meningococcal infection amongst the Muslim population in England followed the outbreak of meningococcal disease associated with the 1987 Haj to Mecca. There were 18 primary cases amongst pilgrims returning from Mecca and 15 subsequent cases among Muslims over the following 19 months. The meningococcal strains were shown to be of the same clone as strains from the Mecca outbreak by possession of an outer membrane protein PI.9. Strains of this group A clone (A III-I) had only rarely been encountered in England before this outbreak.

Adult↗

Characterization of a hot-melt fluid bed coating process for fine granules.

The equipment modifications and process changes necessary to perform hot-melt particle coating in a fluid bed granulator are reviewed. A specific case is presented in which partially hydrogenated cottonseed oil is coated onto fine granules (mean particle size, 77 microns; range, 10-150 microns; one standard deviation is 10 microns) composed of a hydrophobic drug and sucrose. The major variables were product bed temperature, temperature of the wax, spray rate, and atomization air pressure. The product bed temperature was selected to give the optimum congealing rate, and the latter three variables were varied in a statistically designed experiment. The physical properties of wax-coated granules fabricated using combinations of process variables were examined. Response surface analysis was used to determine the optimum process settings in terms of dissolution, particle size, and density of the coated product. This system proved quite adequate for the production of uniformly coated granules, with the best product being obtained at the optimized conditions using 120 degrees C atomization air and molten coating temperature, 30 g/min as the spray rate, and an atomization air pressure of 5 bar.

Capsules↗

Peptide inhibitors of C3 breakdown.

We have investigated the development of substrate-based inhibitors of complement enzymes. Sequences around the scissile Arg77-Ser78 bond of C3 have been synthesized and tested as inhibitors of C3 convertase. The best inhibition was found with the tetrapeptide Ac-Arg-Ser-Asn-Leu-OH (H-576); extending this sequence in either direction reduced inhibitory activity. Preliminary experiments with peptides in which the scissile bond--CO--NH--was replaced with non-hydrolysable moieties such as--CO--CH2--(H-497) and--CH2--NH--(H-336) failed to show enhanced inhibition. One of the longer chain inhibitors H-416 containing DArg77-Ser78 was unexpectedly found to potentiate iC3 cleavage by factors I and H but did not inhibit the intact alternative pathway. The same peptide also bound to factor H. It is concluded that the binding requirements of the C3 convertase are more sophisticated than can be satisfactorily imitated simply by linear sequences around the scissile bond of C3.

Complement Activating Enzymes↗

Genetic diversity of penicillin-binding protein 2 genes of penicillin-resistant strains of Neisseria meningitidis revealed by fingerprinting of amplified DNA.

A 2-kilobase fragment containing the penicillin-binding protein 2 gene (penA) was amplified by using the polymerase chain reaction with DNA prepared from 35 penicillin-resistant strains of Neisseria meningitidis isolated in England, Ireland, and Spain (MICs, 0.16 to 1.28 micrograms of benzylpenicillin per ml) and from 10 penicillin-susceptible strains (MICs, less than or equal to 0.04 micrograms of benzylpenicillin per ml). The penA genes were digested with HpaII or TaqYI; and the resulting fragments were end-labeled, fractionated on a polyacrylamide gel, and autoradiographed, to produce gene fingerprints. The fingerprints of the penA genes of the 10 penicillin-susceptible strains were identical. In contrast, the fingerprints of the penA genes of all but two of the penicillin-resistant strains differed markedly from those of the penicillin-susceptible strains. The altered penA genes of group B penicillin-resistant strains were very diverse, and 14 different fingerprints were found among the 15 strains that we examined. The penA genes of the 19 resistant group C strains were less diverse, and two major fingerprint patterns predominated.

Bacterial Proteins↗

Do non-steroidal anti-inflammatory drugs or smoking predispose to Helicobacter pylori infection?

Susceptibility to Helicobacter pylori infection is a poorly understood phenomenon. This study was undertaken to establish whether either smoking or chronic non-steroidal anti-inflammatory drug (NSAID) consumption might in some way predispose to H. pylori infection and hence lead to peptic ulceration. Serological evidence of H. pylori infection was assessed in 100 consecutive subjects receiving NSAIDs without any evidence of gastrointestinal upset and 100 matched controls. All subjects had a full assessment of their smoking habits. Sixty-three per cent of patients taking NSAIDs compared to 51% of controls had evidence of H. pylori infection (NS). Smoking habit also had no effect on H. pylori colonization. The ulcerogenic potential of NSAIDs and smoking does not appear to be mediated via a prediposition to H. pylori infection.

Adolescent↗

Habituation to irrelevant speech: effects on a visual short-term memory task.

The Baddeley and Hitch (1974) formulation of short-term or working memory embodied a phonological store within the articulatory loop component of the model. Later formulations specifically postulated an acoustic filter that endowed only speech-like stimuli with obligatory access to this phonological store. This paper presents evidence that this phonological store may have two filters, one of which is subject to habituation and can therefore attenuate the entry of irrelevant speech, thus undermining the obligatory access assumption of the model. An experiment is reported in which subjects were presented with a habituation period comprising 20 min of irrelevant speech--speech to be ignored by the subject--before a test phase in which a visually presented serial recall task with concurrent irrelevant speech was performed. The effect of irrelevant speech, which impairs performance on the primary task when there is no habituation phase, is reduced markedly in those conditions where the speech used in the habituation phase is the same as that used in the test phase, if the irrelevant speech is in a language different from that presented during the subsequent trials or if the habituator is a hummed version of the irrelevant speech passage. When a nonspeech sound (pink noise) is used in the habituation phase, a large irrelevant speech effect is found in the test phase. Morris, Quayle, and Jones (1989) found that humming did not produce an irrelevant speech effect, which suggests that the first filter is permeable to humming but that the second filter is not.(ABSTRACT TRUNCATED AT 250 WORDS)

Attention↗

Subcellular distribution of copper in the liver of fetal deer in the last month of gestation.

Fetal deer, in the last month of gestation, accumulate high concentrations of copper in the liver. Livers from fetal deer in late gestation were homogenised and fractionated by continuous sucrose density gradient centrifugation. The distribution of copper closely followed that of DNA; approximately two thirds of the metal was localised to the nuclear fractions with the remaining third in the cytosolic fractions. The fractionation procedure was repeated with digitonin, a lysosomal perturbant: lysosomes were disrupted and the marker enzyme, N-acetyl-beta-glucosaminidase, shifted from the particulate fractions to the cytosolic fractions; the distribution of copper was unaffected. Differential centrifugation of homogenate confirmed that approximately two thirds of the copper was associated with the nuclear fraction. Further confirmation of a nuclear localisation of copper was provided by X-ray microanalysis of purified nuclei.

Animals↗

A prospective study of the prevalence of colonic neoplasms in asymptomatic patients with an age-related risk.

This study was designed to determine the prevalence of colorectal neoplasia in healthy, asymptomatic adults with an age-related risk for colorectal neoplasia. Ninety patients were studied with air contrast barium enema and colonoscopy. The study population included 61 males and 21 females, with an age range of 51-82 yr (65 +/- 2 yr). Adenomatous polyps were found in 27% of males and 14% of females or 24% of patients overall. Sixty-six percent of these neoplasms were above the rectosigmoid junction and the mean size of the polyps was 6.5 +/- 1.2 mm. In two patients, carcinoma was discovered. A linear association between age and the prevalence of colonic neoplasia was not demonstrated. This study demonstrates a relatively high prevalence of colonic neoplasia in patients with an age-related risk.

Adenoma↗