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Biomedical subjects

E M Jones

Publications and source records attributed to E M Jones.

At least 37 records · Page 2Linked to original sources

Three cases of meningococcal pneumonia.

Three cases of pneumonia due to Neisseria meningitidis are described. In all three cases the organism was isolated only from blood cultures, but in the presence of good clinical and radiological evidence of pneumonia. The isolates belonged to three different serogroups: B type 2b, C, and Y. The cases illustrate the fact that N meningitidis can cause pneumonia and that culture of blood plays an important part in the diagnosis. Clinically there is nothing to differentiate meningococcal pneumonia from other causes of community acquired pneumonia. Predisposing factors include aspiration, immunosuppression, influenza, and adenovirus infections. When diagnosed, pneumonia due to N meningitidis should be notified and prophylaxis given as for meningitis or septicaemia.

Adult↗

Cloning of rat and mouse P2Y purinoceptors.

The cellular responses to ATP are mediated by specific high-affinity receptors designated as P2 purinoceptors, five subclasses of which have been defined pharmacologically-P2X, P2Y, P2U, P2T, and P2Z. A cDNA clone encoding a rat P2Y purinoceptor was isolated from an insulinoma cDNA library. The 373-amino acid rat P2Y purinoceptor sequence has 85.7% and 37.8% identity with chicken P2Y and rat P2U purinoceptors, respectively. The sequence of the mouse P2Y purinoceptor was also determined and there was 97.1% amino acid identity with the corresponding rat sequence. RNA blotting studies showed that rat P2Y purinoceptor mRNA was expressed at variable levels in many tissues including heart, brain, spleen, lung, liver, skeletal muscle and kidney, although it was not detected in testis. The cloned rat P2Y purinoceptor was expressed in Xenopus laevis oocytes and possessed the properties expected for this receptor subtype.

Adenosine Triphosphate↗

Antimicrobial chemotherapy of human infection due to Listeria monocytogenes.

Listeriosis is an uncommon infection, but when it occurs it carries a high mortality rate. Early diagnosis is essential and thereafter appropriate antimicrobial chemotherapy. Ampicillin or penicillin plus gentamicin remains the treatment of choice for most manifestations of listeriosis, and adequate doses must be given, i.e. greater than 6g/day of ampicillin or penicillin. Co-trimoxazole appears to be an excellent alternative agent with good penetration into the cerebrospinal fluid. Vancomycin is an appropriate agent for the treatment of primary bacteraemia but does not cross the blood-brain barrier sufficiently well to be useful in meningitis, while erythromycin may be used to treat listeriosis in cases of pregnancy. Treatment of bacteraemia requires one to two weeks' therapy, while meningitis cases may need to be treated for longer; for example, it has been found that most patients with acute meningitis in the UK were treated for 20 days. Infective endocarditis needs treatment for six to eight weeks. Doses should be varied with patients' altered organ function and antimicrobial serum monitoring performed when appropriate.

Anti-Bacterial Agents↗

Age differences in conversational source monitoring.

The present investigation simulated a group conversation in which participants asked (inquirer) and answered (responder) questions, as well as listened to others exchange information. Source (inquirer; responder) identification accuracy was evaluated immediately or after 1 week. Older adults were less adept at source identification, although this difference was reduced with personal (Experiment 2) rather than categorical (Experiment 1) topics. The age difference was independent of explicit memory (cued recall and recognition), suggesting that memory for source and information are separable. Older adults were comparable to younger adults in responder identification but worse at inquirer identification. Responder identification was better than inquirer identification, with the latter dropping to chance at 1 week. Source identification was most accurate when participants were in the responder role; there was little difference between the inquirer and listener roles.

Adolescent↗

Adenosine diphosphate ribosylation of fibroblast growth factor-2.

Basic fibroblast growth factor (FGF-2) is posttranslationally modified by the enzymatic transfer of ADP-ribose from nicotinamide adenine dinucleotide (NAD). When sonicated nuclei of adrenal capillary endothelial or SK-Hep1 cells are incubated with [32P]NAD, FGF-2 is rapidly ADP-ribosylated in a dose- and time-dependent fashion. Proteins structurally related to FGF-2 (FGF-6 and -7) are readily modified, suggesting that they share a common substrate motif. Yet, FGF-1, the most structurally homologous member of the FGF family, is a poor substrate. The reaction is also specific; interleukin-1 alpha, transforming growth factor-alpha, nerve growth factor, insulin-like growth factor-I, and granulocyte macrophage-colony stimulating factor are not substrates for ribosylation. Because the ADP ribosylation of FGF-2 is acid resistant but base and hydroxylamine sensitive, the linkage appears to be mediated through arginine. Most importantly, however, we also establish that endogenous FGF-2 is a substrate for ribosylation. As such, an immunoreactive ADP-ribosylated FGF-2 is detected in extracts of SK-Hep1 nuclei when they are incubated with [32P]NAD. Taken together, these findings suggest that the role played by ADP ribosylation in signal transduction, DNA repair, the control of the cell cycle, and cell differentiation may involve its ability to target molecules such as FGF-2.

Adenocarcinoma↗

Localization of the gene encoding a neutral amino acid transporter-like protein to human chromosome band 19q13.3 and characterization of a simple sequence repeat DNA polymorphism.

The gene encoding a human neutral amino acid transporter-like protein (SLC1A5) was mapped to chromosome band 19q13.3 by fluorescence in situ hybridization to metaphase chromosomes. A simple sequence repeat DNA polymorphism of the form (GT)n was identified in the 3'-untranslated region of SLC1A5 mRNA. Studies in the CEPH families showed significant evidence of linkage between this DNA polymorphism and markers localized to the distal long arm of chromosome 19.

Amino Acid Transport Systems↗

A 10 year survey of the epidemiology and clinical aspects of listeriosis in a provincial English city.

Between January 1983 and December 1992 29 cases of human listeriosis were recorded in Bristol, giving an incidence for the decade of 0.35 infections/10(5) population/annum. For those less than a year old the incidence was 5.2/10(5) population/annum and for adults increased from 0.029/10(5)/annum for those aged 20-49 years to 0.65/10(5)/annum for those over 80 years of age. Social classes I and II were over represented in those infected while classes IV and V were under represented when compared to the general population. Infection was seasonal with most infections occurring in October and 75.9% cases in the last two quarters of the year. Altogether, 13 (45%) cases were associated with pregnancy while 16 (55%) arose in non-pregnant persons. The incidence of pregnancy-associated infection was 1.23 per 10(4) births. In the first half of the decade, pregnancy-associated infection (62.5%) was more common than infection in non-pregnant adults or juveniles but this preponderance was reversed in the second half (23.1%). Among juvenile/adult infections not associated with pregnancy, bacteraemia became more common than CNS infection as the decade progressed. Among the pregnancy-associated infections were five infected abortions, seven neonatal infections (six systemic and one local) and one maternal infection during pregnancy in which the baby was not infected. The juvenile and adult infections in non-pregnant adults presented as primary bacteraemia in 10 (62.5%) patients and CNS infection in six (37.5%) patients. The overall mortality, excluding abortions, was 27.6% (8/29), being 14.3% (1/7) among affected neonates and 37.5% (6/16) among juveniles and non-pregnant adults. Sequelae of infection were not noted in the neonates but a third of the juveniles or adults with CNS infection were left with residual defects.

Adolescent↗

Lactoferricin, a new antimicrobial peptide.

Lactoferricin B (LF-B) is a peptide derived from acid-pepsin digestion of bovine lactoferrin, which has antimicrobial properties. In order to assess the antimicrobial spectrum of LF-B and its possible in vivo uses, the minimum inhibitory and microbicidal concentrations of pure lactoferricin B were determined for a range of bacterial species and under varying conditions of growth including growth phase and size of the inoculum, pH and ionic strength of the medium. Lactoferricin B was bactericidal against a wide range of bacteria and Candida albicans. Proteus spp., Pseudomonas cepacia and Serratia spp. were resistant. The bactericidal activity of LF-B was inhibited by increasing ionic strength and bacterial inoculum and at acid pH. The activity of lactoferricin B was completely inhibited by the addition of 5% whole cow's milk and was reduced in the presence of increasing concentrations of mucin. These results indicate the potential of LF-B to reduce the numbers of organisms in a simple medium, but raise doubts about its role in vivo because of its sensitivity to changes in physical variables. It may be that lactoferricin exerts a transient antimicrobial effect at mucosal surfaces.

Animals↗

Secondary prevention of non-fatal deliberate self-harm. The green card study.

In an attempt to address the low compliance with offers of treatment shown by patients after episodes of non-fatal deliberate self-harm (DSH), patients who had harmed themselves for the first time were offered rapid, easy access to on-call trainee psychiatrists in the event of further difficulties, and they were encouraged to seek help at an early stage should such problems arise. The follow-up data obtained after one year showed a significant reduction of actual or seriously threatened DSH in the experimental group, who also made considerably less demands on medical and psychiatric services, when compared with controls.

Adult↗

Counterregulation during hypoglycemia is directed by widespread brain regions.

Previous studies have demonstrated the importance of the brain in directing counterregulation during insulin-induced hypoglycemia in dogs. The capability of selective carotid or vertebrobasilar hypoglycemia in triggering counterregulation was assessed in this study using overnight-fasted dogs. Insulin (21 pM.kg-1.min-1) was infused for 3 h to create peripheral hypoglycemia in the presence of 1) selective carotid hypoglycemia (vertebral glucose infusion, n = 5), 2) selective vertebrobasilar hypoglycemia (carotid glucose infusion, n = 5), 3) the absence of brain hypoglycemia (carotid and vertebral glucose infusion, n = 4), or 4) total brain hypoglycemia (no head glucose infusion, n = 5). Glucose was infused via a leg vein as needed in each group to minimize the differences in peripheral glucose levels (2.6 +/- 0.1, 3.0 +/- 0.2, 2.7 +/- 0.1, and 2.5 +/- 0.1 mM, respectively). The humoral responses (cortisol, glucagon, catecholamines, and pancreatic polypeptide) to hypoglycemia were minimally attenuated (< 40%) by selective carotid or vertebrobasilar euglycemia. In addition, the increase in hepatic glucose production, as assessed using [3-3H]glucose, was attenuated by only 41 and 34%, respectively, during selective carotid or vertebrobasilar hypoglycemia. These observations offer support for the hypothesis that more than one center is important in hypoglycemic counterregulation in the dog and that they are located in brain regions supplied by the carotid and vertebrobasilar arteries, because significant counterregulation occurred when hypoglycemia developed in either of these circulations. Counterregulation during hypoglycemia, therefore, is probably directed by widespread brain regions that contain glucose-sensitive neurons such that the sensing sites are redundant.

Animals↗

Amplification of a Trypanosoma cruzi DNA sequence from inflammatory lesions in human chagasic cardiomyopathy.

The major cause of morbidity and mortality in Chagas' disease is a chronic inflammatory cardiomyopathy, which presents ten or more years following initial infection. Demonstration of Trypanosoma cruzi in cardiac tissue by routine microscopy or culture is difficult in these patients, which has suggested that persistent organisms are not required for chronic disease. Consequently, studies have focused on elucidating an autoimmune pathogenesis of chronic injury. To further assess the persistence of T. cruzi in host tissue, DNA extracted from formalin-fixed, paraffin-embedded autopsy specimens from seronegative or seropositive patients was amplified by the polymerase chain reaction using T. cruzi-specific primers. Trypanosoma cruzi DNA sequences were not consistently amplified from four seropositive patients who lacked evidence of fatal chronic chagasic cardiomyopathy (CCC) (0 positive of 12 heart samples, 0 positive of four gonadal samples, and 0 positive of four adrenal samples) or nine seronegative patients (0 positive of 27 heart samples, 0 positive of nine gonadal samples and 0 positive of nine adrenal samples). In seven seropositive patients with severe CCC, cardiac tissue adjacent to inflammatory infiltrates yielded amplified T. cruzi DNA sequences in 18 of 21 heart samples. Parallel testing of gonadal and adrenal tissues from these same patients produced detectable T. cruzi DNA in none of the gonadal tissue samples and one of the seven adrenals. Our studies demonstrate that T. cruzi, or a portion of its genome, is present in the inflammatory lesion of chronic cardiac Chagas' disease.

Adult↗

Characterization of inflammatory infiltrates in chronic chagasic myocardial lesions: presence of tumor necrosis factor-alpha+ cells and dominance of granzyme A+, CD8+ lymphocytes.

The inflammatory infiltrates in the heart lesions of chronic chagasic cardiomyopathy are composed predominantly of small lymphocytes with admixed macrophages, plasma cells, and segmented leukocytes. The phenotypes of the lymphoid cells in these infiltrates of human Chagas' disease have not been previously detailed. We used a panel of monoclonal and polyclonal antibodies to immunohistochemically characterize the inflammatory cells in frozen and fixed cardiac tissues from autopsied patients with severe chronic chagasic cardiomyopathy. In all cases, the inflammatory lesions were dominated by CD8+ lymphocytes, many of which expressed granzyme A. A few macrophage-like cells that expressed tumor necrosis factor-alpha were observed in each case. Relatively few natural killer cells or B lymphocytes were found in the lesions. These findings in human chagasic lesions are compatible with concepts that involve cytolysis and fibrosis, and new experimental findings that emphasize potential roles for CD8+ T cells in Chagas' disease.

B-Lymphocytes↗

Expression of major histocompatibility complex antigens and adhesion molecules in hearts of patients with chronic Chagas' disease.

We have previously reported that heart lesions in patients with chronic cardiac Chagas' disease are composed predominantly of granzyme A+, cytolytic CD8+ T lymphocytes. We now pursue this study in the immunopathology of chronic chagasic cardiomyopathy by investigation of the expression of HLA antigens, and adhesion molecules in the hearts of seven chagasic patients with cardiac disease, two asymptomatic chagasic patients, and seven normal controls. Comparative immunohistochemical analyses show that HLA-ABC antigen expression is enhanced on the myocardial cells of chagasic patients with chronic cardiomyopathy, suggesting a possible role for these cells as targets for the CD8+ cytolytic lymphocytes dominant in these lesions. The HLA-DR antigens are not observed on myocardial cells, but are consistently upregulated on the endothelial cells in the hearts of patients with chronic chagasic cardiomyopathy. Intercellular adhesion molecule is expressed by endothelial cells of both chagasic and nonchagasic individuals, but E-selectin was detected only on vessels of hearts from chagasic patients who had chronic cardiomyopathy. Most of the lymphocytes in these lesions express lymphocyte function antigen-1 (LFA-1), CD44, and very late antigen-4, and a few display weak expression of LFA-3. We propose that the expression of these adhesion molecules and major histocompatibility complex antigens by endothelial cells, myocardial cells, and lymphoid cells in these lesions contribute to the pathogenesis of chronic chagasic cardiomyopathy.

Adult↗

Aplasia cutis congenita, cleft palate, epidermolysis bullosa, and ectrodactyly: a new syndrome?

Aplasia cutis congenita (ACC) is a skin disorder in which localized or widespread areas of skin are absent at birth. It has been associated with numerous anomalies and recognizable syndromes. We report a newborn infant with ACC of the scalp, multiple facial abnormalities including cleft palate but not cleft lip, hypoplasia of the distal phalanges of the hands, ectrodactyly of the feet, and epidermolysis bullosa of the extremities and lower trunk. Although this patient had some features that overlapped with ectrodactyly-ectodermal dysplasia-clefting syndrome, the absence of cleft lip and presence of additional skin abnormalities made that diagnosis unlikely. This could represent a newly recognized syndrome of numerous malformations in which ACC is associated with a constellation of previously undescribed structural anomalies.

Abnormalities, Multiple↗

Collagen vascular diseases of childhood.

This article is devoted to collagen vascular diseases of childhood. The connective tissue diseases that are discussed are lupus erythematosus, scleroderma, and dermatomyositis. Of the vasculitic syndromes, Henoch-Schönlein purpura, acute hemorrhagic edema of infancy, and polyarteritis nodosa are discussed. Although the collagen vascular diseases are rare in the pediatric age group, when they occur they can be very serious.

Adolescent↗