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Biomedical subjects

D Jones

Publications and source records attributed to D Jones.

At least 433 records · Page 24Linked to original sources
PubMed1994

Changing patterns in pediatric supraglottitis: a multi-institutional review, 1980 to 1992.

Supraglottitis is a rapidly progressive, life-threatening airway emergency in pediatric patients typically caused by Haemophilus influenzae type B (HIB). With distribution of the first efficacious vaccine for HIB in April 1985, changing disease patterns have begun to emerge; however, certain characteristics have remarkably persisted. The authors reviewed 252 pediatric patients with acute supraglottitis spanning the prevaccination and postvaccination years 1980 to 1992 at three major regional pediatric hospitals in Massachusetts, Ohio, and California, as well as at two community hospitals in Massachusetts. Findings include a decline in disease prevalence in all geographic areas with demographic, etiologic, and management evolution all seen. Children who had been immunized yet developed supraglottitis have been examined as predictive of future trends.

Age Factors↗
PubMed1994

Mercury toxicity.

Explore the source record for details and available documents.

Dental Amalgam↗
PubMed1994

Accuracy of intraoperative staging in colorectal cancer.

In 216 patients with colorectal adenocarcinoma 'operative' and 'final' staging using Duke's classification were compared. The overall 'accuracy' of operative staging was 66% with 17% of tumours understaged and 17% overstaged. The major error was found in nodal staging. If selective peroperative adjuvant therapy is to be considered, efforts should be directed to improve operative nodal staging. Any recommendation for adjuvant perioperative chemotherapy based on operative staging alone will result in a significant number of patients having unnecessary treatment.

Adenocarcinoma↗
PubMed1994

Effect of glucocorticoids on tumor necrosis factor induced suppression of protein synthesis in rat aortic smooth muscle: comparison with extensor digitorum longus.

Protein synthesis was measured in incubated aortic smooth muscle and fast-twitch extensor digitorum longus (EDL) in both sham operated and adrenalectomized (ADX) rats. The studies were performed on four groups: a) untreated controls; b) rats treated with tumor necrosis factor (TNF) @ 50 micrograms/kg. b.w.; c) rats treated with cortisone @ 100 mg/kg/day for 5 days; or d) rats treated with cortisone plus TNF. Both TNF and cortisone suppressed protein synthesis in the aortic smooth muscle and EDL in intact animals. TNF given together with cortisone, induced a significant additional decrease in protein synthesis in both muscle types as compared to cortisone-treated rats. The rate of protein synthesis in aortic smooth muscle from sham operated rats was control > TNF > cortisone > Cortisone+TNF; in the case of EDL, rate was control > cortisone > TNF > Cortisone+TNF. In ADX animals, TNF alone did not affect protein synthesis in both aortic smooth muscle and EDL. Though cortisone alone produced a significant inhibition of protein synthesis, there was no significant further decline in protein synthesis when cortisone was given together with TNF. These findings suggest that the inhibitory effect of TNF on muscle protein synthesis is mediated through glucocorticoids.

Animals↗
PubMed1993

Regulation of human CD44H and CD44E isoform binding to hyaluronan by phorbol myristate acetate and anti-CD44 monoclonal and polyclonal antibodies.

CD44 molecules are comprised of multiple alternatively spliced forms and are associated with diverse functions such as mediation of carcinoma metastasis and T cell coactivation. To study the function of individual CD44 isoforms, we have transfected CD44 isoforms into CD44-negative Jurkat T cells and produced cloned Jurkat cell lines that are stably transfected with either a CD44 isoform containing no alternatively spliced insert (CD44H) or a CD44 variant (CD44E) containing an insert of 132 amino acids derived from exons 12, 13, and 14 of the CD44 gene. We found that neither CD44H- nor CD44E-transfected Jurkat T cells constitutively bound hyaluronan (HA), whereas PMA treatment induced Jurkat cells transfected with CD44H but not CD44E to bind HA. CD44 mAb against noninsert regions of the CD44 extracellular domain (A3D8, A1G3) and polyclonal antisera against the COOH-terminal extracellular glycosaminoglycan region of CD44H (anti-6A serum) both induced CD44H-transfected cells to bind HA, whereas only one CD44 mAb (A1G3) induced CD44E-transfected Jurkat T cells to bind HA. Studies of Jurkat cells transfected with CD44H forms with truncations of the CD44 cytoplasmic domain demonstrated that the cytoplasmic COOH-terminal 52 amino acids were critical for binding of HA to the CD44 extracellular domain. Thus, these data underscore the importance of the CD44 cytoplasmic domain in the function of the extracellular portion of CD44H, and demonstrate a role for ligation of human CD44 isoforms at multiple distinct sites in regulation of expression of CD44 binding to HA.

Amino Acid Sequence↗
PubMed1993

Antibodies against the major brain isoforms of 14-3-3 protein. An antibody specific for the N-acetylated amino-terminus of a protein.

14-3-3 proteins are apparently ubiquitous eukaryotic proteins that comprise a large number of isoforms. They have been implicated in the regulation of a wide range of biological processes [reviewed in Aitken et al. (1992) Trends Biochem. Sci. 17, 498-501]. We have raised specific antibodies against each mammalian brain isoform of 14-3-3 employing peptides synthesised from the amino-terminal regions. The peptides were, like the proteins from mammalian brain, N-acetylated. The antiserum specific for the epsilon isoform did not recognise the recombinant form of this protein (lacking the N-acetyl co-translational modification) expressed in E. coli until it was chemically acetylated.

14-3-3 Proteins↗
PubMed1993

Novel ubiquitin-like ribosomal protein fusion genes from the nematodes Caenorhabditis elegans and Caenorhabditis briggsae.

Among eukaryotes studied to date, homologs of the yeast 76-amino acid ribosomal protein have invariably been found to be cotranslated with ubiquitin. However, in the nematodes Caenorhabditis elegans and Caenorhabditis briggsae, a 70-amino acid domain with only 40% identity to ubiquitin is cotranslated with a homolog of the ribosomal protein. In the nematode ubiquitin-like (UbL) proteins, the nucleotide sequence of the UbL coding region is 92% identical in C. elegans and C. briggsae. The corresponding gene sequence contains a single intron at a location identical to that found in the polyubiquitin gene of C. elegans, further confirming that the ubl genes are evolutionarily related to ubiquitin. The ribosomal protein portion of the UbL polypeptide consists of 93 amino acids and is 68% identical to the human homolog. The ribosomal protein portion of UbL is longer than in other homologs, with the additional sequence being present as a basic carboxyl extension. The ubl gene is constitutively expressed in all life cycle stages of C. elegans. A comparison of the nematode UbL sequences with other ubiquitin-like genes reveals a pattern of sequence conservation, which suggests that the ubiquitin-like proteins may have conserved functional domains.

Amino Acid Sequence↗
PubMed1993

A retinoblastoma-binding protein related to a negative regulator of Ras in yeast.

The growth suppression function of the retinoblastoma protein (Rb) is though to be mediated by Rb binding to cellular proteins. p48 is one of the major proteins that binds to a putative functional domain at the carboxy terminus of the Rb protein. Here we report the isolation of a full-length complementary DNA (RbAp48) encoding p48. Complex formation between p48 and Rb occurs in vitro and in vivo, and apparently involves direct interaction between the proteins. Like Rb, p48 is a ubiquitously expressed nuclear protein. RbAp48 share sequence homology with MSI1, a negative regulator of the Ras-cyclic AMP pathway in the yeast Saccharomyces cerevisiae. Furthermore, like MSI1, human RbAp48 suppresses the heat-shock sensitivity of the yeast ira1 strains and RAS2Val19 strains. Interaction with p48 may be one of the mechanisms for suppression of growth mediated by Rb.

Amino Acid Sequence↗
PubMed1993

Human Ig production and isotype switching in severe combined immunodeficient-human mice.

Severe combined immunodeficient (SCID) mice were transplanted with different human fetal organs (SCID-hu mice), including thymus, liver, spleen, and omentum, and the serum levels of human IgM, IgG, IgE, and IgA were measured. In all SCID-hu mice significant levels (up to 590 ng/ml) of IgM were detected, irrespective of the organs transplanted. In contrast, IgG was present (up to 530 ng/ml) only when the fetal thymus was transplanted together with the fetal liver, indicating that the presence of human T cell is a prerequisite for in vivo isotypes switching by human B cells in SCID-hu mice. Additional transplantation of fetal spleen did not significantly increase IgG levels. was observed 4 months after transplantation. At that time, analysis by IEF showed that human IgG present in SCID-hu serum was at least oligoclonal. Furthermore, all IgG subclasses were represented in the human IgG pool. Human B cells were undetectable in the peripheral blood, spleen, and bone marrow of these SCID-hu mice; in contrast, B cells expressing CD19 could be isolated from the SCID-hu thymus. Considerable proportions of the CD19+ B cells coexpressed CD5, CD7, CD10, CD40, and CD2. These B cells spontaneously produced IgM and IgG in vitro and could be induced to switch to IgE-producing cells when cocultured with cloned activated CD4+ T cells in the presence of IL-4. Collectively, these data demonstrate that functionally mature B cells able to produce IgM and IgG in vivo, and IgE in vitro, are present in the SCID-hu human thymus.

Animals↗
PubMed1993

WAY100135: a novel, selective antagonist at presynaptic and postsynaptic 5-HT1A receptors.

The novel phenylpiperazine derivative, (+/-)-WAY100135 (N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenylpro pionamide dihydrochloride), is a selective antagonist at both somatodendritic and postsynaptic 5-HT1A receptors. The IC50 of (+/-)-WAY100135 at the rat hippocampal 5-HT1A receptor was 34 nM, whereas its IC50 at a range of other receptor sites was > 2 microM. Up to a dose of 2.5 mg/kg i.v. (+/-)-WAY100135 induced a maximum 30% inhibition of raphe neuronal firing and (at 0.5 mg/kg i.v.) antagonised the inhibition of firing induced by 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) in anaesthetised rats. (+/-)-WAY100135 antagonised the action of 5-carboxamidoiodotryptamine in the guinea-pig ileum, with a pA2 of 7.2. (+/-)-WAY100135 had no agonist-like behavioural effects but antagonised the behavioural syndrome and hypothermia induced by 8-OH-DPAT in the rat and mouse, respectively. The interaction of (+/-)-WAY100135 with the 5-HT1A receptor was stereoselective; the (+)-enantiomer being markedly more active in binding, functional and behavioural studies. These data indicate that (+/-)-WAY100135 is the first highly selective antagonist at both somatodendritic and postsynaptic 5-HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Retroviral insertions into a herpesvirus are clustered at the junctions of the short repeat and short unique sequences.

We previously described the integration of a nonacute retrovirus, reticuloendotheliosis virus (REV), into the genome of a herpesvirus, Marek disease virus (MDV), following both long-term and short-term coinfection in cultured fibroblasts. The long-term coinfection occurred in the course of attenuating the oncogenicity of the JM strain of MDV and was sustained for > 100 passages. The short-term coinfection, which spanned only 16 passages, was designed to recreate the insertion phenomenon under controlled conditions. We found that REV integrations into MDV were common and could occur within the first passage following coinfection. Now we have mapped the integration sites. After 5-16 passages in vitro, 17 out of 19 REV junction sites are clustered in two 1-kilobase regions at the junctions of the short unique and short repeat region of MDV. In the long-term cocultivation experiment, 6 out of 10 insertions also mapped in this region. In both cases, integrated proviruses are unstable and undergo subsequent recombinative deletion, often leaving a solitary long terminal repeat. The long terminal repeat sequences are, however, stably maintained for many rounds of passaging in vitro. This clustering of insertions presumably is influenced by selection for viable and fast-growing viruses, and occurs in a region of the MDV genome which shows significant size heterogeneity in several strains.

Animals↗
PubMed1993

Bacterial superantigens mediate T cell deletions in the mouse severe combined immunodeficiency-human liver/thymus model.

The ability to analyze T cell receptor (TCR) thymic repertoire shaping in humans by self and foreign ligands is hampered by the lack of suitable models. We recently documented that the mouse severe combined immunodeficiency (SCID)-human fetal liver/thymus model recapitulates the TCR V beta gene repertoire of human thymocytes. Here, we show that an exogenous superantigen, staphylococcal enterotoxin B, administered to such mice induces clonal deletions in both CD4+8- and CD8+4- cells involving the same human V beta clones that are selected in vitro by this toxin. This model, therefore, may allow comprehensive studies into the effects of microbial and other agents on human T cell thymic selection processes in a biologically relevant setting.

Animals↗
PubMed1993

Serum interleukin 6 levels are elevated in lymphoma patients and correlate with survival in advanced Hodgkin's disease and with B symptoms.

Several cytokines including gamma-interferon, tumor necrosis factor alpha, interleukin 1 beta (IL-1 beta), and interleukin 6 (IL-6) are pyrogenic and can inhibit lipogenic processes. Because patients with lymphoma often suffer from fever, weight loss, and night sweats (B symptoms), the etiology of which is unknown, the authors investigated serum levels of these cytokines in normal volunteers and in patients with Hodgkin's and non-Hodgkin's lymphoma. Sixty serum samples from patients with Hodgkin's disease (28 patients) or non-Hodgkin's lymphoma (32 patients), as well as 20 samples from normal volunteers, were collected. The majority of patients had advanced (Stage III or IV) or relapsed disease. The assay for gamma-interferon was a specific and sensitive radioimmunoassay (lower limit of detection = 0.1 unit/ml); the assays for tumor necrosis factor alpha, IL-1 beta, and IL-6 were enzyme-linked immunoassays with lower limits of sensitivity of 10 pg/ml, 20 pg/ml, and 22 pg/ml, respectively. There were no statistically significant differences in gamma-interferon, tumor necrosis factor alpha, or IL-1 beta levels between lymphoma patients and normal subjects. In contrast, 20 of 57 patients (35%) with lymphoma as compared with 0 of 19 normal volunteers (0%) had detectable serum IL-6 levels (P < 0.005, chi 2 test). Interestingly, 17 of 29 lymphoma patients with B symptoms (59%) as opposed to 3 of 28 lymphoma patients without B symptoms (11%) had detectable serum IL-6 levels (P < 0.001, chi 2 test); the median IL-6 level was 28.9 pg/ml (B symptoms present) versus undetectable (no B symptoms) (P < 0.005, Mann-Whitney U test). Analyzing Hodgkin's and non-Hodgkin's lymphoma groups separately revealed similar results. IL-6 levels showed no significant correlation with time from diagnosis, beta 2-microglobulin, or lactate dehydrogenase levels. However, analysis by the method of Kaplan and Meir demonstrated that the median survival of Hodgkin's disease patients with detectable IL-6 levels (> or = 22 pg/ml) was 10 mo, whereas the median survival has not been reached at a median follow-up time of 37.5 mo in those patients with lower values (Wilcoxon P value = 0.0012). There were too few patients in each subset of non-Hodgkin's lymphoma to determine the correlation between IL-6 and survival but, considered as a single group, a statistically significant correlation was not found.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗