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Biomedical subjects

K Gould

Publications and source records attributed to K Gould.

At least 37 records · Page 2Linked to original sources
PubMed1995

Vaccinia virus serpins B13R and B22R do not inhibit antigen presentation to class I-restricted cytotoxic T lymphocytes.

Vaccinia virus (VV) inhibits the presentation of certain epitopes from influenza virus nucleoprotein (NP), haemagglutinin (HA) and non-structural 1 (NS1) proteins to CD8+ cytotoxic T lymphocytes (CTL) by an unknown mechanism. We have investigated whether VV genes B13R and B22R, which encode proteins with amino acid similarity to serine protease inhibitors (serpins), are involved in this process. Recombinant VVs were constructed which express influenza virus proteins HA, NP or NS1 and which lack serpin gene B13R or both B13R and B22R. The lysis of cells infected with these viruses by influenza virus-specific CD8+ CTL was compared to the lysis of cells infected with viruses expressing both the influenza proteins and the serpin genes. Cytotoxicity assays showed that deletion of the VV serpin genes B13R and B22R and other genes between B13R and B24R did not increase the level of lysis, indicating that these genes are not involved in inhibition of antigen presentation of the epitopes tested.

Animals↗
PubMed1994

The life span of new neurons in a song control nucleus of the adult canary brain depends on time of year when these cells are born.

The number of high vocal center (HVC) neurons labeled in adult male canaries by systemic injections of [3H]thymidine depended on season and survival time. This was true for HVC neurons projecting to the robust nucleus of the archistriatum and for other HVC neurons that could not be retrogradely filled from the robust nucleus of the archistriatum. Birds injected in October and killed 40 days later had twice as many labeled HVC neurons as birds injected in May and killed 40 days later. However, this difference became much larger (5 times) when the birds were allowed to survive for 4 months. Whereas more than half of the spring-born neurons disappeared between 40 days and 4 months, there was no reduction in the number of fall-born neurons present at the 4-month survival point. We infer that seasonal variables affect the life span of HVC neurons born in adulthood.

Aging↗
PubMed1994

Prevention of hepatitis B infection: a survey of surgeons and interventional cardiologists.

Hepatitis B immunization and the use of protective measures against blood contamination were assessed in a group of clinicians associated with invasive procedures. A self-administered confidential questionnaire was sent to 140 surgeons and interventional cardiologists, of whom 105 (75 per cent) replied. Ninety-five respondents (90 per cent) were immunized against hepatitis B, most (63 per cent) by an occupational health department and the majority within 5 years of this study. Only 80 per cent had had their immunity tested after immunization. Barrier protective techniques were used infrequently, with 30 per cent of respondents wearing impermeable gowns, 14 per cent wearing visors and 9 per cent using double-gloving for all procedures. Department of Health guidelines on protection from hepatitis B were published after this survey and the implementation of these guidelines in an NHS trust hospital is discussed.

Cardiology↗
PubMed1994

A note on transfer of stimulus control in the delayed-cue procedure: facilitation by an overt differential response.

This case study describes initially unsuccessful attempts to use the delayed-cue procedure to teach conditional discriminations to an individual with moderate mental retardation. The task was matching printed-word comparison stimuli to dictated-name sample stimuli. In three experiments, the subject typically waited for the delayed cue unless differential responses to the dictated samples (repeating the sample names) were required. Hence, the study provides an example of a way to make the delayed-cue method more effective. The stimulus control bases for the results are discussed.

Adult↗
PubMed1994

Breast cancer prevention: a summary of the chemoprevention trial with tamoxifen.

PURPOSE/OBJECTIVES: To review the Breast Cancer Prevention Trial, which is testing tamoxifen as a chemoprevention agent. DATA SOURCES: Published articles and books; National Surgical Adjuvant Breast Project protocols. DATA SYNTHESIS: Because tamoxifen has proven to be an effective hormonal agent in the treatment of all stages of breast cancer and because it has a low side effect rate, a national study is under way to determine its effects as a breast cancer preventive agent. CONCLUSIONS: Results of this double-blind, placebo-controlled study will be available at the study's completion in 1997. IMPLICATIONS FOR NURSING PRACTICE: Providing patients with education, informed consent assistance, and help in adjusting to the drug's side effects and influences on quality of life.

Breast Neoplasms↗
PubMed1994

Inhibition of thrombosis by a selective fibrinogen receptor antagonist without effect on bleeding time.

Membrane glycoprotein alpha IIb beta 3 on platelets plays a pivotal role in hemostasis by mediating RGD-(arginine-glycine-aspartic acid)-dependent platelet adhesion and aggregation. Antagonists of alpha IIb beta 3 ligand binding function, such as antibodies, snake venom peptides, or synthetic RGD-containing peptides can completely inhibit platelet aggregation in vitro and cause significant prolongation of bleeding times when injected into experimental animals. The in vitro and in vivo properties of an alpha IIb beta 3 specific RGD-containing peptide 2G (G(Pen)GHRGDLRCA) were compared to two non-specific RGD-containing peptides 1N (G(Pen)GRGDTPCA) and 2H (GRGDSPDG). All three peptides have similar IC50 values in human platelet aggregation (14-22 microM) and ELISA-based alpha IIb beta 3 receptor assays (0.2-0.3 microM) but show different inhibitory activity (IC50 values) in the alpha v beta 5 (2G = 10 microM; 1N = 0.06 microM; 2H = 0.05 microM) and alpha 5 beta 1 receptor assays (2G = 8.3 microM; 1N = 0.06 microM; 2H = 0.04). The alpha IIb beta 3 specific peptide 2G had no effect on monolayers of human saphenous vein endothelial cells while 1N and 2H caused many cells to detach and contract. Peptides 2G and 1N inhibited ADP-stimulated ex vivo platelet aggregation in dogs in a dose dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Peptides shorter than a minimal CTL epitope may have a higher binding affinity than the epitope for the class I Kk molecule.

A previously published Kk-specific motif was used to predict that an optimal Kk-restricted epitope within the nucleoprotein (NP) of influenza A/PR/8/34 virus corresponds to sequence SDYEGRLI (residues 50-57). Although this is the minimal epitope recognized by murine cytotoxic T lymphocytes (CTL), its binding affinity for the Kk molecule is increased following removal of either the N-terminal amino acid residue (S) or the N-terminal dipeptide (SD). A possible explanation for this unexpected result is that interactions between the C-terminus of the epitope and the Kk molecule contribute to the binding energy to a much greater extent than interactions between the N-terminus of the epitope and the Kk molecule.

Amino Acid Sequence↗
PubMed1993

Culture of Mycobacterium kansasii in the blood of an HIV negative patient.

A 23 year old man with a congenital myelodysplastic disorder and fibrosing lung disease received treatment with prednisolone. After nine months his condition deteriorated and Mycobacterium kansasii was isolated from blood cultures and lymph node biopsy specimens. He responded to antituberculous treatment. M kansasii has not previously been isolated from the blood stream of HIV negative patients.

Adult↗
PubMed1992

A defect in the presentation of intracellular viral antigens is restored by interferon-gamma in cell lines with impaired major histocompatibility complex class I assembly.

Surface expression of the majority of class I major histocompatibility complex (MHC) heavy chains is known to require assembly with beta 2 microglobulin (beta 2m). To define other factors involved in class I MHC assembly, we have studied two tumor cell lines that are deficient in cell surface class I (H-2) expression. The BC2 fibrosarcoma and the CMT lung carcinoma express only intracellular unassociated heavy chains despite the presence of beta 2m. As described previously, when these cell lines are treated with interferon-gamma (IFN-gamma), they are capable of assembling and transporting class I molecules to the cell surface. In this study, we have shown that in the absence of IFN-gamma these mutant cells are unable to present intracellular viral antigens, although they can be lysed by specific cytotoxic T lymphocyte (CTL) after pre-incubation with the corresponding synthetic peptide. Flow cytometric analysis demonstrated that extracellular peptide was capable of increasing twofold the surface expression of beta 2m-heavy chain complexes. Furthermore, immunoprecipitation experiments confirmed that peptide stabilizes chain association in the BC2 cell lysates. However, infecting these mutants with vectors expressing either pre-processed antigen or rapidly degraded antigen, failed to overcome their defect in the presentation of endogenous peptide to specific CTL or to mediate surface expression of class I MHC. Preincubation with IFN-gamma completely reversed the endogenous peptide presentation defect, even in mutant cells transfected with a vector encoding a cDNA for the H-2 molecule restricting CTL recognition. This last result suggests that IFN-gamma corrects the defect by a mechanism separate from simple enhancement of the number of class I molecules produced by the cell. Because there is growing evidence that endogenous peptides can participate in class I MHC assembly, the defect in these mutants could be ascribed to the lack of access to class I molecules by the endogenous peptide. This would prevent stable association of the heavy and light chains and their subsequent transport. Our data suggests that IFN-gamma reestablishes class I MHC surface expression by restoring access of endogenously synthesized peptide to class I molecules.

Amino Acid Sequence↗
PubMed1992

Determinants of graft arteriosclerosis after heart transplantation.

Accelerated graft coronary artery disease (TxCAD) is now the most common complication limiting long-term survival after heart transplantation. This study examines its association with several potentially causative factors. The study population comprised all 73 transplants recipients at this centre between May 1985 and June 1989 who survived at least 2 years. Coronary angiography was performed in every patient at 2 years after transplantation and annually thereafter. All angiograms were retrospectively examined for any evidence of TxCAD. The number of rejection episodes and history of cytomegalovirus (CMV) infection were determined from patient records. Fasting serum triglycerides, and total and HDL cholesterol were measured at between 18 and 60 months after transplantation. Patients with advanced TxCAD (> 70% stenoses) had a mean of 1.4 +/- 1.4 rejection episodes in the first year compared with 0.5 +/- 0.8 episodes in those without TxCAD (P < 0.05). The mean number of episodes in all patients with any evidence of TxCAD was 0.8 +/- 1.1 which was not significantly different from those without TxCAD. There were no association between exposure to CMV infection and TxCAD or between hyperlipidaemia and TxCAD. We conclude that frequent episodes of allograft rejection are associated with the development of advanced TxCAD. Hyperlipidaemia is not associated with the development of TxCAD in the first 5 years after transplantation. A history of exposure to CMV is not associated with TxCAD in our patients possibly because of our routine use of anti-CMV hyperimmune globulin in CMV-mismatched patients.

Adult↗
PubMed1991

Successful treatment of Bacillus cereus infection with ciprofloxacin.

Bacillus cereus is rarely a pulmonary pathogen but may cause pneumonia in immunocompromised patients. A patient with bronchiectasis and no recognisable immunodeficiency had this organism isolated during two infective exacerbations, once from respiratory secretions and once by blood culture. Ciprofloxacin treatment was effective on both occasions.

Adult↗
PubMed1991

Modification of the thrombogenicity of a self-expanding vascular stent.

When placed in the iliac arteries of normal healthy animals, the Wall-stent self-expanding endovascular prosthesis exhibits minimal thrombogenicity, measured by 111In-labeled platelet uptake. Preliminary clinical reports suggest a greater thrombogenicity in diseased human arteries. When evaluated in an ex vivo shunt, these stents exhibit significant thrombogenicity. The ex vivo shunt may therefore provide a model to evaluate strategies to reduce thrombogenicity in the clinical setting. Stents were released into shunts and the uptake of In111-labeled platelets was measured by gamma imaging for 2 h at a flow rate of 100 mL/min. The effect of systemic heparin, 100 U/kg, oral aspirin, 325 mg, and local application of heparin-benzalkonium chloride complex were evaluated. At the end of each study the stents were fixed in situ and evaluated with scanning electron microscopy (SEM). Control stents exhibited a rapid, significant uptake of platelet associated 111In activity, which reached a maximum in approximately 1 h. Twenty-two percent of control stents occluded before 2 h. Aspirin reduced maximum platelet uptake by 46%. Systemic heparin, with a clotting time greater than five times control, reduced maximum platelet uptake by 86%. The benzalkonium-heparin complex coating, with no increase in clotting time, reduced maximum platelet uptake by 84%. No occlusions were observed with the anti-thrombotic regimes. SEM evaluation of the stents supports the results of the isotope uptake studies.

Animals↗
PubMed1989

A 15 amino acid fragment of influenza nucleoprotein synthesized in the cytoplasm is presented to class I-restricted cytotoxic T lymphocytes.

A recombinant vaccinia has been designed to express amino acids 366-379 of influenza nucleoprotein, previously shown to be the minimal epitope recognized by a class I-restricted cytotoxic T cell clone. Target cells infected with the recombinant vaccinia virus expressing this peptide are recognized by CTL as efficiently as target cells expressing the complete nucleoprotein. The results imply the existence of a peptide transport system that constitutively passes the products of degraded proteins from the cytoplasm into a membrane-bound compartment of the cell.

Animals↗