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Biomedical subjects

J Gordon

Publications and source records attributed to J Gordon.

At least 235 records · Page 13Linked to original sources

Surveillance of attempted suicide among adolescents in Oregon, 1988.

In January 1988, Oregon became the first state to require hospital-based reporting of attempted suicide (AS) in all adolescents less than 18 years old. From January to December 1988, 644 cases of AS were reported (annual rate of 214 per 100,000 population, ages 10 to 17 years). We compared these 644 cases of AS with all 137 Oregon adolescents less than 18 years old who committed suicide in Oregon during the 10-year-period 1979 through 1988, and found that the strongest predictor of outcome was method used.

Adolescent↗

Expression of human recombinant CD23 in insect cells.

Human CD23 (low affinity receptor for IgE) has been expressed in insect cells (Sf9) using the baculovirus expression system and the baculovirus transfer vector pAc373. Insect cells infected with a recombinant baculovirus coding for CD23 synthesized a polypeptide not found in wild-type infected insect cells that had antigenic properties similar to natural CD23 produced in RPMI 8866 cells. Surface expression of recombinant CD23 was demonstrated by its ability to bind IgE. Recombinant CD23 expressed in insect cells had a slightly lower molecular weight (43 kDa) than that of natural CD23 (45 kDa) from RPMI 8866 cells as detected by SDS-PAGE followed by Western-blotting. Affinity-purified recombinant CD23 from infected insect cells showed B-cell growth promoting activitiy. These observations demonstrate for the first time that biologically active recombinant CD23 can be produced by the baculovirus expression system, thus providing a useful source of recombinant material to elucidate the biological functions of CD23.

Animals↗

Leukotriene B4 potentiates the expression and release of Fc epsilon RII/CD23, and proliferation and differentiation of human B lymphocytes induced by IL-4.

This study documents the influence of leukotriene (LT) B4 on human B lymphocyte responses. Incubation of freshly isolated B lymphocytes with LTB4, but not LTC4, induced a slight but significant, time- and dose-dependent increase in the surface expression of Fc epsilon RII/CD23 and class II MHC Ag and in the release of soluble CD23. These changes were maximal at 10 nM LTB4 after an incubation period of 48 h. When B lymphocytes were preactivated in vitro with Staphylococcus aureus Cowan strain I (SAC), neither LTB4 nor LTC4 was able to promote proliferation and/or IgG and IgM secretion. In contrast, when resting B lymphocytes were stimulated with a suboptimal concentration (3 U/ml) of IL-4, LTB4, but not LTC4, potentiated both the Fc epsilon RII/CD23 and the class II MHC antigen expression, and the release of soluble CD23 in a dose-dependent manner, without affecting the kinetics of these responses. Furthermore, LTB4, but not LTC4, amplified both the proliferative response and the IgG and IgM secretion induced by addition of a suboptimal dose of IL-4 (3 U/ml) to SAC-preactivated B lymphocytes. Again, LTB4 did not modify the kinetics of the proliferative response promoted by IL-4. Although LTB4 potentiated IL-4-induced IgG and IgM secretion from SAC-activated B lymphocytes, no production of IgE was observed. These data indicate that LTB4 could play a regulatory role in the modulation of IL-4-induced signaling in human B lymphocytes.

Antigens, CD↗

Interleukin 4 activates human B lymphocytes via transient inositol lipid hydrolysis and delayed cyclic adenosine monophosphate generation.

We report from three independent centers that, in human tonsillar B lymphocytes, human IL4 switches on a series of second messenger changes, the precise sequence of which constitutes a novel signal transduction cascade. It involves an immediate and transient elevation of inositol 1,4,5-trisphosphate and Ca2+ levels. This is followed several minutes later by a sustained rise in cellular cyclic adenosine monophosphate concentration, the triggering of which involves both the Ca2+ rise and an additional, as yet unidentified, IL4-generated signal. Both the products of the initial inositol lipid hydrolysis and the delayed cyclic adenosine monophosphate accumulation are essential for the later induction of CD23 expression, a major phenotypic change promoted in these cells by IL4. The striking contrast between these findings and those that have been observed for the IL4 triggering of murine B cells is discussed.

Antigens, Differentiation, B-Lymphocyte↗

Intact, 45-kDa (membrane) form of CD23 is consistently mitogenic for normal and transformed B lymphoblasts.

When isolated from lysates of the RPMI 8866 B lymphoblastoid cell line, the CD23 antigen was found to be present be in two forms corresponding to the intact 45-kDa membrane species and to a 25-kDa product that is more usually found as a released fragment in the extracellular medium. By contrast with preparations of extracellular species of CD23 which were seen to be variable in their biological activity, cell-associated CD23 was consistently mitogenic both for autogenous transformed B lymphoblasts and for pre-activated normal B cells. Addition to the normal cocktail of protease inhibitors of N alpha-tosyl-L-lysine chloromethylketone (TLCK), which has selectivity for trypsin-like serine proteases, resulted in preparations of CD23 from RPMI 8866 cell lysates that were exclusively in the 45-kDa intact form; such material retained full and reliable activity in the biological assays. The implications of these observations for the autocrine control of B lymphocyte growth are discussed.

Antigens, CD↗

Functional implication for the topographical relationship between MHC class II and the low-affinity IgE receptor: occupancy of CD23 prevents B lymphocytes from stimulating allogeneic mixed lymphocyte responses.

Following the observation of Bonnefoy et al. (J. Exp. Med. 1988. 167:57), that the low-affinity IgE receptor (CD23) on B lymphocytes can be coupled (with the use of chemical cross-linking reagents) to major histocompatibility complex (MHC) class II DR molecules, we now report that ligands binding within the lectin-homology region of CD23 prevent B cells from stimulating allogeneic mixed lymphocyte responses. Ligands capable of blocking mixed lymphocyte responses include the anti-CD23 antibodies MHM6 and EBVCS 4 but not EBVCS 1 and 5. IgE itself, and small peptides representing sequences within the CH3 domain of IgE. The detailed topographical relationship between CD23 and MHC class II on the B lymphocyte surface was examined using dual immuno-fluorescence labeling of cells and direct visualization of the staining by confocal laser scanning microscopy. On transformed B lymphoblasts, the two antigens were seen to co-localize in discrete patches; on normal B cells which had been cultured for 2 days with interleukin 4, CD23 and MHC class II converged at a single pole which exhibited a tendency to pseudopod formation and provided a focus for homotypic cell-cell interactions. The possibility that CD23 could serve as a co-stimulatory-adhesion molecule in antigen presentation by B lymphocytes is discussed with special reference to a potential role in the regulation of IgE synthesis.

Antibodies, Monoclonal↗

Immunoelectron microscopical visualization of ribonucleoproteins in the chromatoid body of mouse spermatids.

The chromatoid body (CB), a cytoplasmic organelle present only in germ cell line, was studied at the electron microscopic level in mouse spermatids using cytochemical techniques and specific antibodies directed against sn-RNPs, hnRNPs, and ribosomal proteins. We found that specific staining for DNA as well as the use of monoclonal anti-DNA antibodies show a complete absence of DNA in the CB. The CB remains stained, however, after the application of the ethidium bromide-PTA technique, suggesting the presence of RNA within this organelle. snRNP as well as hnRNP proteins are demonstrated within the CB by means of specific monoclonal or polyclonal antibodies, especially during earlier spermiogenic stages. Monoclonal antibodies directed against the large ribosomal subunit proteins P1/P2 detect these antigens on the CB essentially along the internal threads of dense fibrillar material. Our findings suggest that the CB may function as a source of mRNA and/or of its partially processed precursors during the late stages of spermiogenesis, when the spermatid nucleus becomes gradually inactive.

Animals↗

Trajectory control in targeted force impulses. VII. Independent setting of amplitude and direction in response preparation.

We have previously shown that when aiming impulses of force to unpredictable flexion and extension targets, subjects prepare themselves to respond by preselecting a default amplitude and direction. In our preceding study, where flexion and extension target ranges were symmetrical, subjects prepared a single default amplitude near the center of each of the two ranges and selected a default direction arbitrarily (Favilla, Hening et al. 1989). Following target presentation, amplitude and direction were specified gradually and in parallel. By using an experimental paradigm in which target amplitudes had unequal probabilities in only one of the two directions, we no sought to determine to what extent the default amplitude prepared by subjects is dependent on the default direction that is selected for a given trial. Five normal subjects produced isometric elbow flexion and extension force impulses to match four targets requiring responses of two amplitudes in each direction. Flexion and extension targets were of the same size. In all biased probability conditions, targets were presented in unpredictable order and, in one direction, the probability of occurrence of the targets was biased (80% versus 20%). In the other direction, the two targets were equiprobable. To maximize the effect of the default settings on response parameters, we required subjects to initiate their response in synchrony with a predictable tone occuring less than a reaction time subsequent to the presentation of the visual target. Such a short interval was chosen to disclose the default parameters selected by limiting the influence of the target just presented on the amplitude and direction of the subjects' responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The relationship of prostaglandins to cAMP, IgG, IgM and alpha-2-macroglobulin in gingival crevicular fluid in chronic adult periodontitis.

Gingival crevicular fluid, collected from 8 patients with chronic adult periodontitis before and 21 days after root planing and scaling, was analysed for prostaglandin E2, 6KPGF1 alpha, cAMP, IgG, IgM and alpha-2-macroglobulin, and their inter-relationship evaluated. There was a significant decrease in the levels of prostaglandin E2, IgG, IgM and alpha-2-macroglobulin after treatment, whereas the levels of 6KPGF1 alpha and cAMP remained essentially unchanged. The level of prostaglandin E2 decreased by 35%, IgG by 32%, IgM by 90%, and alpha-2-macroglobulin by 79%. There was a significant degree of correlation between prostaglandin E2 and 6KPGF1 alpha and cAMP before treatment but not after, but no correlation between prostaglandin E2 and IgG, IgM and alpha-2-macroglobulin either before or after. This correlation pattern indicates the involvement of E2, prostaglandin 6KPGF1 alpha and cAMP in inflammation in the periodontium. The changes in IgG, IgM and alpha-2-macroglobulin reflect yet another mechanism of host response which appears to be independent of prostaglandins.

6-Ketoprostaglandin F1 alpha↗

Trisomy 3 in cold agglutinin disease.

Cold agglutinin disease (CAD) is a form of autoimmune hemolytic anemia generally considered to result from an antibody-producing clonal expansion of B lymphocytes. We studied 16 patients with CAD and demonstrated a chromosomally abnormal clone in the peripheral blood (PB) of six. Trisomy 3 was the only abnormality in two patients, trisomy 12 the only abnormality in one, and both trisomy 3 and trisomy 12 were present in three patients. A lymphoma was subsequently diagnosed in two of these six patients and in none of the patients without a karyotypic abnormality. The results suggest that trisomy 3 confers a slight growth advantage in the B-cell lineage, particularly at a relatively late stage of differentiation. The resultant clone may present clinically as CAD and, in some cases, progress to a clinical lymphoma.

Anemia, Hemolytic, Autoimmune↗

The predictive value of zona-free hamster egg sperm penetration assay for failure of human in vitro fertilization and subsequent successful zona drilling.

The value of various sperm parameters and the zona-free hamster egg sperm penetration assay (SPA) in predicting human in vitro fertilization (IVF) failure and subsequent successful fertilization with zona drilling was assessed. In 19 couples, throughout 31 IVF cycles, a total of 153 oocytes failed to be fertilized. In subsequent 12 cycles with zona drilling, 33 of 131 (25%) were fertilized. The incidence of teratospermia and asthenospermia was significantly higher in the study group than in the control, 74% versus 32% and 42% versus 5%, respectively. Although the mean values for the performance of sperm in SPA and fertilization of human eggs after zona drilling were remarkably similar (28 +/- 6 versus 28 +/- 4), there was no correlation between individual parameters (r = 0.15). Thus, whereas male factor infertility is more likely to be associated with teratoasthenospermia, neither the SPA nor other sperm parameters have any predictive value for failure in IVF. In addition, no criterion of sperm function has yet been identified that would eliminate oligoteratoasthenozoospermic males from consideration of IVF with zona drilling.

Cervix Mucus↗

Differential cholecystokinin gene expression in brain and gut of the fasted rat.

Cholecystokinin (CCK) gene expression has been compared in the brain and duodenum of control and 5 days fasted rats. To study transcription, CCK mRNA was quantified using a solution hybridization assay. Large and small molecular weight CCK peptides were separated using a sequential extraction process and subsequently quantified by radioimmunoassay. In the duodenum, a fall in weight was paralleled by a decrease in CCK mRNA and in the large forms of CCK peptides. Small molecular species of CCK peptides did not change. There was no change in weight, CCK transcriptional or translational products in the brain as a whole. These data indicate location-specific differential regulation of the products of CCK gene expression in the fasted rat.

Animals↗

Epstein-Barr virus nuclear antigen 2 induces expression of the virus-encoded latent membrane protein.

Infection of Epstein-Barr virus-negative human B-lymphoma cell lines with the fully transforming B95.8 Epstein-Barr virus strain was associated with complete virus latent gene expression and a change in the cell surface and growth phenotype toward that of in vitro-transformed lymphoblastoid cell lines. In contrast, the cells infected with the P3HR1 Epstein-Barr virus strain, a deletion mutant that cannot encode Epstein-Barr nuclear antigen 2 (EBNA2) or a full-length EBNA-LP, expressed EBNAs1, 3a, 3b, and 3c but were negative for the latent membrane protein (LMP) and showed no change in cellular phenotype. This suggests that EBNA2 and/or EBNA-LP may be required for subsequent expression of LMP in Epstein-Barr virus-infected B cells. Recombinant vectors capable of expressing the B95.8 EBNA2A protein were introduced by electroporation into two P3HR1-converted B-lymphoma cell lines, BL30/P3 and BL41/P3. In both cases, stable expression of EBNA2A was accompanied by activation of LMP expression from the resident P3HR1 genome; control transfectants that did not express the EBNA2A protein never showed induction of LMP. In further experiments, a recombinant vector capable of expressing the full-length B95.8 EBNA-LP was introduced into the same target lines. Strong EBNA-LP expression was consistently observed in the transfected clones but was never accompanied by induction of LMP. The EBNA2A gene transfectants expressing EBNA2A and LMP showed a dramatic change in cell surface and growth phenotype toward a pattern like that of lymphoblastoid cell lines; some but not all of these changes could be reproduced in the absence of EBNA2A by transfection of P3HR1-converted cell lines with a recombinant vector expressing LMP. These studies suggest that EBNA2 plays an important dual role in the process of B-cell activation to the lymphoblastoid phenotype; the protein can have a direct effect upon cellular gene expression and is also involved in activating the expression of a second virus-encoded effector protein, LMP.

Antigens, Viral↗

Efficacy of clindamycin hydrochloride in refractory periodontitis: 24-month results.

The purpose of this investigation was to evaluate the use of clindamycin hydrochloride in the treatment of adult refractory periodontitis. Thirty patients with a history of unsuccessful treatment with scaling, periodontal surgery, and the use of tetracyclines were entered into the study. Upon entry, the suspected refractory patients were scaled several times and then monitored for the presence of active disease by probing attachment level measurements performed in duplicate. Active disease was defined as a 3.0 mm or greater loss in attachment from the baseline examination or the occurrence of a periodontal abscess. When active disease was detected, patients were treated with scaling and clindamycin 150 mg qid for 7 days. Patients served as their own controls. Twenty four patients demonstrated further attachment loss following scaling alone and were treated with clindamycin hydrochloride. Scaling and clindamycin treatment decreased the incidence of active disease from an annual rate of 8.0% to 0.5% of sites per patient (P less than .001). The mean time required to detect the first active site increased from 4.9 +/- 3.7 months following scaling alone to 16.7 +/- 7.6 months following scaling and clindamycin (P less than 001). Active sites lost an average of 3.1 mm of probing attachment following scaling alone but "gained" back 2.0 mm at 6 months and 1.5 mm at 24 months post-antibiotic and scaling treatment. Bleeding on probing was significantly reduced (P less than .05) from 31.8% of sites pre-clindamycin treatment to 12.3% at 12 months and 17.9% of sites at 24 months post-clindamycin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗