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Biomedical subjects

W Jackson

Publications and source records attributed to W Jackson.

At least 37 records · Page 2Linked to original sources

Bone marrow and splenic granulocyte-macrophage colony-stimulating factor and transforming growth factor-beta mRNA levels in irradiated mice.

The effects of a myeloablative sublethal 775 cGy 60C gamma radiation exposure on endogenous bone marrow (BM) and splenic granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor-beta (TGF-beta) mRNA levels were assayed in B6D2F1 female mice. BM and spleen were harvested from normal mice and irradiated mice on days 2, 4, 7, 10, and 14 after exposure. Cytokine mRNA levels were determined using reverse transcription-polymerase chain reaction. After irradiation, GM-CSF mRNA levels were significantly increased in the BM from days 2 to 10 and in the spleen from days 4 to 10. However, when BM and splenic GM-CSF protein levels were measured using Western dot blot, no increased protein levels were detected. Serum GM-CSF levels were likewise unchanged. Radiation exposure did not affect BM or splenic TGF-beta mRNA levels and this cytokine is known to be produced by cell populations similar to those that produce GM-CSF. These data suggest that radiation injury to hemopoietic tissues results in differential effects on GM-CSF and TGF-beta mRNA levels and that, in the case of GM-CSF, increased mRNA levels are not matched by increased protein production.

Agranulocytosis↗

Varicella-zoster virus glycoprotein gpI/gpIV receptor: expression, complex formation, and antigenicity within the vaccinia virus-T7 RNA polymerase transfection system.

The unique short region of the varicella-zoster virus (VZV) genome contains two open reading frames which encode glycoproteins designated gpI and gpIV (herpes simplex virus homologs gE and gI, respectively). Like its herpesviral counterpart gE, the VZV gpI gene product functions as a cell surface receptor (V. Litwin, W. Jackson, and C. Grose, J. Virol. 66:3643-3651, 1992). To evaluate the biosynthesis of the two VZV glycoproteins and further explore their relationship to one another, the two glycoprotein genes were individually cloned into a pTM1 vector under control of the T7 promoter. Transfection of the cloned gpI or gpIV construct into HeLa cells previously infected with vaccinia recombinant virus expressing bacteriophage T7 polymerase resulted in a much higher level expression of each VZV glycoprotein than previously achieved. Synthesis of both gpI and gpIV included intermediary partially glycosylated forms and mature N- and O-linked final product. Transfections in the presence of 32Pi demonstrated that the mature forms of both gpI and gpIV were phosphorylated, while similar experiments with [35S]sulfate showed that only the mature gpI was sulfated. When gpI and gpIV were coexpressed in the same cell, the two glycoproteins were complexed to each other, as both proteins could be immunoprecipitated by antibodies against either gpI or gpIV. Coprecipitation did not occur as a result of a shared epitope, because gpI expressed alone was not precipitated by antibody to gpIV, and gpIV expressed alone was not precipitated by antibody to gpI. Pulse-chase analysis demonstrated that the gpI-gpIV association occurred early in processing; furthermore, this complex formation interfered with posttranslational modifications and thereby reduced the M(r)s of the mature forms of both gpI and gpIV. Similarly, the molecular masses of the cotransfected gene products corresponded with those of the infected cell glycoproteins, a result which suggested that authentic gpI and gpIV were ordinarily found within a complex. Thus, the adjacent open reading frames 67 and 68 code for two glycoproteins which in turn form a distinctive sulfated and phosphorylated cell surface complex with receptor properties.

Antibodies, Monoclonal↗

Identification of the phosphorylation sequence in the cytoplasmic tail of the varicella-zoster virus Fc receptor glycoprotein gpI.

Varicella-zoster virus (VZV) glycoprotein gpI, the homolog of herpes simplex virus gE, functions as a receptor for the Fc portion of immunoglobulin G. Like other cell surface receptors, this viral receptor is highly phosphorylated in cell culture. To identify the precise location of the cellular kinase-mediated phosphorylation, we generated a tailless deletion mutant and several point mutants which had altered serine and threonine residues within the cytoplasmic domain of gpI. The mutated and wild-type genes of gpI were transfected and expressed within a vaccinia virus-T7 polymerase transfection system in order to determine what effect these mutations had on the phosphorylation state of the protein in vivo and in vitro. Truncation of the cytoplasmic domain of gpI diminished the phosphorylation of gpI in vivo. Examination of the point mutants established that the major phosphorylation sequence of gpI was located between amino acids 593 and 598, a site which included four phosphorylatable serine and threonine residues. Phosphorylation analyses of the mutant and wild-type glycoproteins confirmed that gpI was a substrate for casein kinase II, with threonines 596 and 598 being critical residues. Although the mutant glycoproteins were phosphorylated by casein kinase I, protease V8 partial digestion profiles suggested that casein kinase II exerted the major effect. Thus, these mutagenesis studies demonstrated that the gpI cytoplasmic sequence Ser-Glu-Ser-Thr-Asp-Thr was phosphorylated in mammalian cells in the absence of any other herpesvirus products. Since the region defined by transfection was consistent with results obtained with in vitro phosphorylation by casein kinase II, we propose that VZV gpI is a physiologic substrate for casein kinase II. Immunofluorescence and pulse-chase experiments demonstrated that the mutant glycoproteins were processed and transported to the outer cell membrane.

Amino Acid Sequence↗

Immune response to Prevotella intermedia in patients with recurrent nonstreptococcal tonsillitis.

The role of three oral flora organisms (Prevotella intermedia, Porphyromonas gingivalis, and Actinobacillus actinomycetemcomitans) was investigated in 31 children with recurrent nonstreptococcal tonsillitis. Antibody titers to the three organisms were measured by enzyme-linked immunosorbent assay in the 31 patients, as well as in 32 control patients who had not suffered from recurrent tonsillitis. None of the individuals in either group suffered from periodontal or dental illness. Significantly higher antibody levels to P intermedia were found in the study group as compared to controls (median 91.0 versus 72.5; p = .02). In contrast, the antibody titers to the other two organisms were generally low (less than 0.30), and no difference was found among the two study groups. The elevated antibody levels to P intermedia, a known oral pathogen that is also isolated from most recurrently inflamed tonsils, suggest a pathogenic role for this organism in recurrent tonsillitis.

Adult↗

Developing a computerized ambulatory medical record to document health promotion and disease prevention activities during the clinic encounter.

The authors believe that the computerized medical record may enhance physician-delivered preventive services by providing timely individual feedback. Additionally, we note that interest in health promotion and disease prevention in the medical community as well as the general population has been increasing during the last decade. In response to this increased interest, we believe that health promotion and disease prevention activities should be conducted by every clinician and should include basic measures such as immunizations, appropriate screening tests, and advice and counseling about lifestyle. Additional investigation into the use of computers and computer-generated reminders to enhance the delivery of preventive services is needed.

Ambulatory Care Information Systems↗

Receptor properties of two varicella-zoster virus glycoproteins, gpI and gpIV, homologous to herpes simplex virus gE and gI.

The varicella-zoster virus (VZV) genome contains 70 reading frames (ORF), 5 of which encode the glycoproteins gpI, gpII, gpIII, gpIV, and gpV. ORF 67 and 68 lie adjacent to each other in the unique short region of the VZV genome and code for gpIV and gpI, respectively. These two genes, which are contained within the HindIII C fragment of the VZV genome, were subcloned in the correct orientation downstream from the promoter regions of the eukaryotic expression vectors pCMV5 and pBJ. After transfection, 5 to 20% of the Cos cells bound antibody specific for the given glycoprotein. In this study, it was shown that only the cells transfected with the gpI construct bound to the Fc fragment of human immunoglobulin G. Neither the transfected gpIV gene product nor the vector only bound to the Fc fragment. Thus, VZV gpI is confirmed to be the VZV-encoded Fc-binding glycoprotein. Like the wild-type form of gpI expressed in VZV-infected cells, gpI precipitated from transfected cells contained both N-linked and O-linked glycans and was heavily sialated. In addition, the transfected gpI gene product was phosphorylated both in cell culture and in protein kinase assays by mammalian casein kinases I and II. Extensive computer-assisted analyses of the VZV gpI sequence, as well as those of alphaherpesviral homolog glycoproteins, disclosed properties similar to those of other cell surface receptors; these included (i) exocytoplasmic regions rich in cysteine residues, (ii) membrane-proximal regions with potential O-linked glycosylation sites, and (iii) cytoplasmic domains with consensus phosphorylation sites.

Amino Acid Sequence↗

Pilocarpine treatment of salivary gland hypofunction and dry mouth (xerostomia).

We studied the effects of pilocarpine hydrochloride, a para-sympathomimetic agent, on major salivary gland output and subjective responses in 31 patients with salivary hypofunction. Pilocarpine hydrochloride (5-mg capsules, three times daily) was given for 5 months and a placebo was randomly assigned for 1 month in a double-blind fashion. Objective measurements of major salivary gland output, subjective impressions of oral moisture, treatment-related side effects, and a number of physiologic measures were assessed monthly. Pilocarpine significantly increased salivary output in 21 of the 31 patients. Subjective improvement in the feeling of oral dryness, speaking, chewing, and swallowing were reported by 27 individuals. Side effects, while common, generally were mild and tolerable. There were no significant alterations in cardiovascular or other physiologic measures. We conclude that pilocarpine is an effective and safe treatment for salivary gland hypofunction and xerostomia in selected patients. The increase in major gland output provides beneficial natural secretions and relief of oral dryness.

Adolescent↗

Phosphorylation of varicella-zoster virus glycoprotein gpI by mammalian casein kinase II and casein kinase I.

Varicella-zoster virus (VZV) glycoprotein gpI is the predominant viral glycoprotein within the plasma membranes of infected cells. This viral glycoprotein is phosphorylated on its polypeptide backbone during biosynthesis. In this report, we investigated the protein kinases which participate in the phosphorylation events. Under in vivo conditions, VZV gpI was phosphorylated on its serine and threonine residues by protein kinases present within lysates of either VZV-infected or uninfected cells. Because this activity was diminished by heparin, a known inhibitor of casein kinase II, isolated gpI was incubated with purified casein kinase II and shown to be phosphorylated in an in vitro assay containing [gamma-32P]ATP. The same glycoprotein was phosphorylated when [32P]GTP was substituted for [32P]ATP in the protein kinase assay. We also tested whether VZV gpI was phosphorylated by two other ubiquitous mammalian protein kinases--casein kinase I and cyclic AMP-dependent kinase--and found that only casein kinase I modified gpI. When the predicted 623-amino-acid sequence of gpI was examined, two phosphorylation sites known to be optimal for casein kinase II were observed. Immediately upstream from each of the casein kinase II sites was a potential casein kinase I phosphorylation site. In summary, this study showed that VZV gpI was phosphorylated by each of two mammalian protein kinases (casein kinase I and casein kinase II) and that potential serine-threonine phosphorylation sites for each of these two kinases were present in the viral glycoprotein.

Amino Acids↗

Effect of nitroglycerin ointment placement on the severity of headache and flushing in patients with cardiac disease.

Fifty-six patients with cardiac disease participated in a study to determine the effect of site placement on patient reports of headache and flushing after topical nitroglycerin ointment placement. Nitroglycerin was placed on the upper arm, chest, and pelvis in random order. Approximately 30 minutes after application, patients were asked to evaluate their headache and flushing using a visual analogue scale. No significant difference in the severity of side effects was found when the three sites were compared by multivariate analysis of variance with repeated measures. The clinical practice of instructing patients to vary the site placement of nitroglycerin ointment to avoid side effects was not supported.

Administration, Cutaneous↗

Correlative clinical biochemistry and hematological profiles of laboratory-bred Bolivian squirrel monkeys (Saimiri sciureus).

Twenty-five clinical and biochemical parameters were determined on 17 normal, male, laboratory-bred Bolivian squirrel monkeys (Saimiri sciureus). Parallel hematologic parameters were conducted. The correlation of biochemical and hematological observations and the distribution characteristics, range, and standard error of the mean were determined. The purpose of the present communication is to establish baseline biochemical values for laboratory-bred squirrel monkeys and to present a correlative comparison between selected cellular elements and major blood electrolytes.

Animals↗

A radioimmunoassay for plasma dehydroepiandrosterone sulphate incorporating placental steroid sulphatase as a hydrolysing reagent.

We describe a method for the measurement of plasma dehydroepiandrosterone sulphate (DHAS) which incorporates a Triton X-100 solubilised preparation of human placental steroid sulphatase as a hydrolysing agent and a direct radioimmunoassay of liberated DHA using a specific antiserum. The hydrolysis procedure is carried out at 50 degrees C for 1 h and an assay run can be completed in 4 h. As determined by the method, plasma concentrations of DHAS in 32 normal adult men (ages 23-58 yr) had a mean value +/- SD of 5.5 +/- 1.89 mumol/l. For 30 normal adult cyclic women (ages 22-35 yr) the mean plasma concentration of DHAS +/- SD was 3.1 +/- 1.35 mumol/l which was significantly lower (P less than 0.01) than found for men. Plasma DHAS concentration were also measured in 50 hirsute female patients. The mean value +/- SD was 5.03 +/- 2.52 mumol/l which was significantly higher (P less than 0.01) than the value for the normal female group. Some 42% of the hirsute patients had DHAS concentrations above the upper 95% probability limit of the normal range for premenopausal women.

Adult↗

The Overt Aggression Scale for the objective rating of verbal and physical aggression.

The authors describe the design and reliability of a rating scale that measures aggressive behaviors in adults and children. On the Overt Aggression Scale (OAS), aggression is divided into four categories: verbal aggression, physical aggression against objects, physical aggression against self, and physical aggression against others. In addition, specific interventions related to each aggressive event can be recorded on the OAS. The clinical and research applications of this scale are discussed.

Adolescent↗

Hematologic values of normal Bolivian squirrel monkeys (Saimiri sciureus): a comparison between wild-caught and laboratory-bred male animals.

Complete and differential blood counts were conducted on 23 male squirrel monkeys (Saimiri sciureus) of Bolivian origin. The sample included 9 laboratory-bred and 14 wild-caught adult monkeys weighing between 600 and 1,500 g. The means of total white blood cell (WBC) counts, total hemoglobin and hematocrits of laboratory-bred animals were found to be significantly different from those of wild-caught monkeys (p less than 0.01). Other hematologic parameters showed no significant differences between the two experimental groups. 3 of 14 (21.0%) wild-caught animals each had 1 reactive lymphocyte and 7% of the same group had 10 nucleated erythrocytes per 100 WBC. No reactive lymphocytes or nucleated erythrocytes were observed in laboratory-bred animals. The importance of these baseline data and the basis for the differences observed between laboratory and wild-caught monkeys are discussed within the context of experimental studies involving primates in which hematologic parameters are valuable.

Animals↗

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Hospitals↗

Imipramine-induced inappropriate ADH secretion.

This case demonstrates the occurrence of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in association with the administration of several antidepressant medications. The SIADH was shown by rechallenge to be associated with imipramine, an antidepressant not previously associated with SIADH. In addition, SIADH appeared to occur with bupropion, a new antidepressant structurally dissimilar to tricyclic antidepressants.

Aged↗