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Biomedical subjects

D M Jones

Publications and source records attributed to D M Jones.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1992

Meningococcal infections in England and Wales: 1991.

There were fewer reports of cases of meningococcal infection in England and Wales during 1991 than in 1990. The number of isolates received at the Meningococcal Reference Laboratory decreased by 102 (7%), largely due to fewer strains being received from South West Thames, North East Thames and North Western regions. Group C infections showed a greater decrease than group B, with 16% fewer strains reported in 1991 than in 1990. Eight per cent of the strains received during 1991 showed reduced susceptibility to penicillin (MIC > 0.16mg/l).

Adolescent↗
PubMed1992

The serum resistance of gonococci in the majority of urethral exudates is due to sialylated lipopolysaccharide seen as a surface coat.

Examined before subculture, gonococci in 18 urethral exudates collected from different patients were serum-resistant. For 15 exudates, the resistance was drastically reduced by treatment with neuraminidase and by one subculture on laboratory media. It was restored by incubation with cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA). Electron microscopic examination of gonococci in eight exudates showed a surface structure stained by Ruthenium red which disappeared in most samples when they were treated with neuraminidase. These results were identical with those of previous studies on in vitro grown gonococci which had shown that serum resistance is due to sialylation of a 4.5-kDa conserved component of gonococcal lipopolysaccharide (LPS) by host CMP-NANA, which masks the target site for bactericidal IgM and renders surface LPS stainable by Ruthenium red. The serum resistance of gonococci in the remaining three exudates was not reduced by neuraminidase nor by subculture. The mechanism of this stable resistance is unknown.

Blood Bactericidal Activity↗
PubMed1992

Wegener's granulomatosis masquerading as pancreatic carcinoma.

A 62-year-old male presented with painless jaundice and solitary pulmonary and pancreatic masses. An extensive evaluation revealed Wegener's granulomatosis as the etiology. His pancreatic mass and jaundice responded to temporary stenting and therapy with cyclophosphamide and prednisone. While pancreatic vasculitis in Wegener's granulomatosis has been noted previously in autopsy studies, symptomatic involvement has been reported only once previously and never as a presenting feature of the disease. The antineutrophil cytoplasmic antibody (ANCA) assay proved useful in establishing the diagnosis. Necrotizing vasculidities can mimic pancreatic carcinoma and should be considered in the differential diagnosis of atypical cases.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1992

The lipooligosaccharide immunotype as a virulence determinant in Neisseria meningitidis.

We have studied the antigenic (immunotype) and physical characteristics of the lipooligosaccharide (LOS) of epidemiologically related Neisseria meningitidis case (36) and carrier (76) isolates associated with a virulent clone of meningococci (ET-5 complex). LOS immunotypes were determined by dot blotting using immunotype specific monoclonal antibodies and physical characteristics were determined from silver stained SDS-PAGE following proteinase K digestion. The genetic similarity of the different isolates was confirmed by analysis of the restriction fragment length polymorphisms. An association between LOS immunotype expression and invasive disease was found; 97% of case isolates expressed the L3,7,9 immunotype, of which 13% additionally expressed the L1,8,10 determinant. The LOS immunotypes of carrier strains were much more heterogeneous. The predominant immunotype was L1,8,10 (70%) and only 24% expressed L3,7,9 alone. Genotypically related case isolates from Norway (6) and Austria (18) expressed the L3,7,9 immunotype with similar frequency to the U.K. isolates. The combination of LOS immunotype and capsule expression appears to be related to the virulence of these meningococcal strains.

Antibodies, Bacterial↗
PubMed1992

The development of a microwave fluid-bed processor. I. Construction and qualification of a prototype laboratory unit.

The static bed- and planetary-type microwave dryers currently available to process pharmaceutical materials are not designed to use hot-air fluidization for the purpose of maximizing microwave energy inputs and particle drying. To take advantage of the benefits offered by fluidization, a 1-kg Uni-Gatt laboratory fluid bed processor was modified to support microwave-assisted fluid bed drying of several representative pharmaceutical granulations. The construction, design features, and validation of this new microwave fluid bed processor are presented.

Calibration↗
PubMed1992

H. pylori, the most common bacterial infection in Africa: a random serological study.

This study was carried out to determine the prevalence of antibodies to Helicobacter pylori in northern Nigeria, a region with a low incidence of peptic ulceration. In a random, serological survey of 268 subjects, 228 (85%) of the population studied had IgG antibodies to H. pylori. Fifty-eight of these subjects had experienced dyspepsia in the preceding 6 months. The majority of the population (82%) is infected between the ages of 5 and 10. Despite the high prevalence of antibodies to H. pylori, peptic ulcer is uncommon, suggesting that H. pylori is not important in the etiology of peptic ulcer in this population. Indeed, most patients infected by H. pylori are asymptomatic. The possible reasons for this are discussed.

Adolescent↗
PubMed1991

Influenza A and meningococcal disease.

There are several anecdotal accounts of the association between outbreaks of influenza and meningococcal disease. The exceptional increase in the number of cases of meningococcal infection 2 weeks after an influenza A outbreak in England and Wales during November and December, 1989, provided an opportunity to investigate the relation between the two events. Patients with meningococcal disease in December, 1989, were more likely than age-matched controls to show serological evidence of recent influenza A infection (odds ratio 3.9, 95% Cl 1.2-13.9). The most likely explanation for the association is immune suppression induced by influenza A, though a lowering of mucosal resistance to meningococcal invasion may also be a factor. Public health authorities should be aware of the association and should be prepared to alert medical practitioners and the public to the increased risk of meningococcal disease when influenza A outbreaks occur.

Adult↗
PubMed1991

Point mutation in meningococcal por A gene associated with increased endemic disease.

The por A gene, which encodes expression of meningococcal class 1 outer membrane protein, responsible for antigenic subtype specificity, has been cloned and sequenced in an isolate of Neisseria meningitidis (B:15:P1.7,16) from a patient in the Gloucester area with meningococcal meningitis. Comparison of the sequence with that of the equivalent gene from the P1.7,16 reference strain reveals a point mutation which generates a single aminoacid change in the epitope responsible for P1.16 specificity. Monoclonal antibodies with P1.16 specificity do not react with synthetic peptides that correspond to the altered epitope, and do not promote complement-mediated bactericidal killing of the isolate. Analysis of other strains shows widespread distribution of infections due to B:15:P1.7,16 meningococci with the altered epitope (P1.16b) in England and Wales.

Antibodies, Monoclonal↗
PubMed1991

Successful engraftment of human postnatal thymus in severe combined immune deficient (SCID) mice: differential engraftment of thymic components with irradiation versus anti-asialo GM-1 immunosuppressive regimens.

To develop a model of human thymus growth in vivo, we have implanted postnatal human thymus under the renal capsule of severe combined immune deficient (SCID) mice and assayed for graft survival and graft characteristics 1-3 mo after engraftment. Three groups of SCID mice were engrafted with postnatal human thymus: untreated SCID mice, SCID mice pretreated with 400 cGy of gamma irradiation 1-5 d before engraftment, and SCID mice treated with intraperitoneal anti-asialo GM-1 antiserum every 4-5 d during engraftment. In the untreated group of SCID mice, only 37% of grafts survived and consisted of human thymic microenvironment components and human immature thymocytes. Irradiation of SCID mice before engraftment improved survival of human thymic grafts to 83%, but these grafts were largely devoid of thymocytes and contained only thymic microenvironment components with large numbers of thymic macrophages. Treatment of SCID mice with anti-asialo GM-1 antiserum throughout the engraftment period also promoted human thymus engraftment (70%) and induced SCID B cell Ig production (SCID[Ig+]) in 38% of animals. In SCID(Ig-) anti-asialo GM-1-treated mice, the human thymic grafts were similar in content to those in untreated SCID mice. However, in anti-asialo GM-1-treated animals with grafts that became SCID(Ig+), all animals were found to have mouse-human chimeric grafts in that the human thymic microenvironment (human fibroblasts, thymic epithelium, vessels) was colonized by murine T cells. These data demonstrate that human postnatal thymus will grow as xenografts in SCID mice, and that the components of human thymus that engraft are dependent on the immunosuppressive regimen used in recipient mice. A striking finding in this study was the induction of T and B lymphopoiesis in SCID mice by abrogation of NK cell activity with in vivo anti-asialo GM-1 treatment. These data strongly suggest that asialo GM-1+ NK cells and/or macrophages play a role in mediation of suppression of lymphopoiesis in SCID mice.

Animals↗
PubMed1991

Chemoprophylaxis of meningitis.

Chemoprophylaxis of meningitis caused by Neisseria meningitidis and Haemophilus influenzae may be determined by the epidemiology of transmission, the antibiotic susceptibility patterns of the organisms, and the usage of vaccines. A review of transmission in England distinguishes differences in sporadic and cluster meningococcal infections. Because of resistance to sulphadiazine, rifampicin and ciprofloxacin are prophylactic agents of choice. Vaccination can be a useful adjunct to antibiotic prophylaxis. Prophylaxis for meningitis due to H. influenzae type b can be provided by rifampicin and vaccination can also be an adjunct to antibiotic prophylaxis.

Ciprofloxacin↗
PubMed1991

The surface structure seen on gonococci after treatment with CMP-NANA is due to sialylation of surface lipopolysaccharide previously described as a 'capsule'.

Phenotypic serum resistance of gonococci in urethral exudates is due to sialylation of lipopolysaccharide (LPS) by host cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA). A surface structure was visible on gonococci [strain BS4 (agar)] that had been stained with ruthenium red after incubation with CMP-NANA. This structure was not visible after neuraminidase treatment, which released sialic acid but not LPS. The LPS profiles of strain BS4 (agar) had another in vivo-selected strain Gc40 (variant D1), were similar. A monoclonal antibody (mAb) which recognises epitope C on the LPS of 'capsulated' gonococci was shown by immunoblotting to react with several LPS components, including one of about 4.5 kDa which contains the probable site of sialylation by CMP-NANA. The reactions with the mAb were not affected by growing the strains with CMP-NANA nor by neuraminidase treatment of the sialylated LPS. The mAb also gold-labelled the surface of both strains before and after treatment with CMP-NANA. These data indicate that sialylation by CMP-NANA and staining with ruthenium red renders more visible the surface LPS which, sometimes in the past, has been seen as a 'capsule'.

Antibodies, Monoclonal↗