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Biomedical subjects

S Grace

Publications and source records attributed to S Grace.

11 recordsLinked to original sources

Cytomegalovirus-specific cellular immune responses and viremia in recipients of allogeneic stem cell transplants.

The immune suppression inherent in allogeneic stem cell transplantation (SCT) offers a favorable environment for infection by opportunistic agents, such as human cytomegalovirus (CMV). Despite the application of potent antiviral prophylaxis, patients remain at risk for CMV infection until adequate immunity is restored. CMV-specific CD8(+) T cell counts were monitored, using HLA-A2 tetrameric complexes, to establish the level of immune response to the viral phosphoprotein UL83 in patients after allogeneic SCT. Correlating this with viral replication and clinical status shows that the level of tetramer-positive T cells provides an assessment of CMV immune reconstitution after stem cell transplantation. Most patients with seropositive donors did reconstitute long-term CMV immunity, unless prolonged immunosuppression to control graft-versus-host disease was induced. Together with polymerase chain reaction testing, this technique provides measurable parameters that can be a guide to therapeutic decision making and can form the basis of CMV immunotherapy.

Adolescent↗

Sequential annual administration of purified fusion protein vaccine against respiratory syncytial virus in children with cystic fibrosis.

BACKGROUND: We recently showed the clinical benefit of the PFP-2 vaccine for respiratory syncytial virus (RSV) for children with cystic fibrosis (CF). OBJECTIVE: To determine the safety and immunogenicity of yearly sequential administration of the PFP-2 vaccine in CF children. STUDY DESIGN: Twenty-nine of the 34 CF children who participated in the previous study were enrolled in this open label vaccine study. All of the CF children ages 2.6 to 8.9 years received the PFP-2 vaccine, the PFP/PFP group received the PFP-2 vaccine in 1993 and 1994 and the saline/PFP group received the vaccine for the first time in 1994. At entry demographic data and measurements of lung function and nutrition were collected. Microneutralization test, enzyme-linked immunosorbent assay to F protein and Western blot assay were performed on plasma drawn before and 4 weeks after vaccination and at the end of the RSV season. During the study weekly telephone calls were made and acute respiratory illnesses were evaluated. RESULTS: Baseline measurements were similar between groups. Systemic and local vaccine reactions were mild and similar for both groups. A 4-fold or greater neutralizing antibody rise to RSV occurred in 4 of 14 (28.6%) and 9 of 14 (64.3%) in PFP/PFP and saline/PFP groups (P = 0.13), respectively. Four children in the PFP/PFP group and 7 in the saline/PFP group were infected with RSV. A reduction in lower respiratory illnesses (1.0 vs. 2.0), antibiotic courses (2.5 vs. 5.6) and days of illnesses (37.3 vs. 93.1) was observed in the PFP/PFP vaccinees infected with RSV compared with the saline/PFP group (t test; P < or = 0.05). One death occurred in the PFP/PFP group; the cause of death was consistent with septic shock and unrelated to vaccination or RSV infection. CONCLUSION: Sequential annual PFP-2 vaccination was safe and not associated with exaggerated respiratory disease.

Antibodies, Viral↗

Purified fusion protein vaccine protects against lower respiratory tract illness during respiratory syncytial virus season in children with cystic fibrosis.

OBJECTIVE: To test in a double blind, placebo-controlled study a purified fusion protein (PFP-2) vaccine against respiratory syncytial virus (RSV) in RSV-seropositive children with cystic fibrosis (CF). METHODS: Seventeen CF children, mean age 4.5 years, received PFP-2 vaccine and 17 CF children, mean age 5.8 years, received a saline vaccine. At enrollment the Shwachman clinical score, Brasfield radiographic score, oxygen saturation (SpO2), anthropometric indices and other variables were recorded. After vaccination the reactions were assessed daily for 7 days. During the RSV season weekly telephone interviews were performed and children with an acute respiratory illness were evaluated and cultured for RSV. Serum was drawn before vaccination, 1 month after vaccination and at the end of the RSV season and tested for antibodies to RSV. RESULTS: Other than age the baseline measurements at enrollment were similar between groups. The PFP-2 vaccine produced mild local reactions and induced a significant neutralizing antibody response in two-thirds of the vaccinees and a significant enzyme-linked immunosorbent assay-fusion glycoprotein antibody response in nearly all the PFP-2 vaccinees. Vaccine-enhanced disease was not observed in PFP-2 vaccines infected with RSV. Protection against RSV infection was not observed; however, a significant reduction (t test, P < 0.01) in mean number of lower respiratory tract illnesses (0.8 vs. 2.1), antibiotic courses (2.2 vs 4.5) and days ill (30.5 vs. 67) occurred among RSV-infected PFP-2 vaccinees. CONCLUSIONS: Efficacy of the PFP-2 vaccine against lower respiratory tract illness during the RSV season was shown in RSV-seropositive children with CF.

Child↗

The use of mouse serum and the presence of non-adherent cells for the culture of mouse macrophages.

Mouse serum (MS) was investigated as an alternative to fetal calf serum (FCS) as a medium supplement for the culture of murine macrophages. Peritoneal macrophages were successfully cultured in medium supplemented with 1-20% MS and were able to produce superoxide anions in response to stimulation with phorbol myristate acetate (PMA) and to phagocytose antibody-coated erythrocytes effectively. Macrophages cultured in the presence of 5% or 20% FCS showed a generally augmented response to PMA, raising the possibility that they had been 'primed' by constituents or contaminants of FCS. Lipopolysaccharide-elicited macrophages initially showed vigorous in vitro responses to PMA which decreased with increasing culture time in MS-supplemented medium. This 'de-differentiation' of elicited macrophages could be due to the absence of LPS contamination and foreign protein when autologous serum is used as a medium supplement. In all cultures the presence of non-adherent cells for the first 24 h increased the number and superoxide response of adherent cells. MS is a convenient, reliable and inexpensive alternative to FCS as a medium supplement for murine macrophage cultures.

Animals↗

Kaposi's sarcoma in Zimbabwe. II. Peripheral lymphocytes, immunoglobulin G levels and HIV antibody positivity.

Patients with Kaposi's Sarcoma (KS) were grouped according to their clinical symptoms into "indolent", "locally aggressive", "endemic generalised aggressive" and "epidemic generalised aggressive" disease. Only the patients in the epidemic generalised aggressive disease group had serum antibodies to HIV. Complete peripheral blood counts, including lymphocyte subsets, and serum IgG assays were performed on all patients before treatment was initiated. In all the aggressive disease groups there was evidence of immune deficiency in that T helper/inducer (T4) cells were reduced leading to reduced T4,T8 (suppresser/cytotoxic) ratio. All patient groups had increased levels of serum IgG. Although immune deficiency and aggressive KS can be explained in the HIV infected patients no underlying cause has been found in the HIV negative patients with aggressive KS.

HIV Antibodies↗

Child abuse within the ear, nose and throat.

Non-accidental injuries to the ear, nose and throat are inevitably difficult to detect because of their covert nature. A survey of 50 hospitals and all NSPCC child abuse units in England was carried out to determine the type of injuries that were inflicted to these regions in verified cases of abuse. The importance of detecting these injuries is emphasized to permit intervention and prevent escalation of injury.

Child Abuse↗

Relationship between non-antigen-specific immunodepression and persisting immune complexes induced by pertussis in mice.

A temporal relationship has been demonstrated between persisting immune complexes and non-antigen-specific immunodepression. Mice were given intraperitoneal injections of Bordetella pertussis at weekly intervals. After 7 weeks they developed circulating immune complexes, the levels of which increased with continued administration of pertussis. The increase in immune complex levels was accompanied by a diminished primary immune response to intraperitoneally injected sheep erythrocytes (SRBC) as judged by a reduction in their direct and indirect plaque-forming cell response and serum agglutination titres. Spleen cells from immunodepressed pertussis-treated mice were transferred to irradiated normal recipients and displayed a normal response to SRBC. By contrast, spleen cells transferred from normal donors to irradiated pertussis-treated recipients had an impaired response to SRBC. Thus, the immunodepression caused by pertussis treatment is a property of the environment and not the lymphocytes themselves. It is considered that chronic circulating immune complexes induced by pertussis administration may cause non-antigen-specific immunodepression.

Animals↗

Examination of the solvent perturbation technique as a method to identify enzyme catalytic groups.

The present study was undertaken for the purpose of evaluating the solvent perturbation technique as a method to identify enzyme catalytic residues. For establishment of expected directions and sizes of pKa perturbations for different types of acids in different classes of solvents, a study of the pKa of a series of acids in mixed solvent systems was carried out. Consistent with previous findings, the presence of organic solvents (25% v/v) increased the pKa values of neutral acids while it decreased or did not change the pKa values of cationic acids. The size of the perturbation observed was dependent on the nature of the organic solvent and on the polarity of the neutral form of the acid. The solvent perturbation studies were then extended to the catalytic aspartate residue of yeast hexokinase. The pKa of this residue was determined from the MgATP V/K profile measured in the presence and absence of organic solvents (25% v/v). While dimethylformamide and methanol induced small but perhaps significant increases in the observed pKa, dimethyl sulfoxide and propylene glycol did not. The pKa values, from the MgATP V/K profiles measured in the presence of fully saturating glucose, were not significantly increased by the organic solvents. The pKi vs. pH profile for the competitive inhibitor lyxose was also measured in the presence and absence of organic solvents. While methanol (25% v/v), dimethylformamide (25% v/v), and dioxane (17.5% v/v) induced a large increase in the pKa, propylene glycol and dimethyl sulfoxide (25% v/v) did not. The results from this investigation indicate that the solvent perturbation technique should not be relied upon indiscriminately.

Adenosine Triphosphate↗

Segmental gastric antral resection in experimental peptic ulceration.

In using the technique of histamine in beeswax peptic ulceration in dogs, these experimental preparations were studied as to their efficacy to protect against ulceration: laparotomy controls; bilateral truncal vagotomy and pyloroplasty; a 50 per cent gastrectomy and vagotomy plus a Billroth II gastrojejeunostomy; a 50 per cent segmental resection of the gastric antrum and corplus plus bilateral truncal vagotomy and pyloroplasty; a 75 per cent gastrectomy and Billroth II gastrojejeunostomy, and a 75 per cent segmental resection of the gastric antrum and corpus and bilateral truncal vagotomy and pyloroplasty. Only a 75 per cent gastrectomy Billroth II and a 75 per cent segmental resection of the antrum and corpus plus vagotomy and pyloroplasty consistently protected against histamine in beeswax induced ulceration.

Animals↗