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Biomedical subjects

J Sedgwick

Publications and source records attributed to J Sedgwick.

At least 19 recordsLinked to original sources
PubMed1998

Differential expression of synaptosome-associated protein 25 kDa [SNAP-25] in hippocampi of neonatal mice following exposure to human influenza virus in utero.

We investigated the role of maternal exposure to human influenza virus [HI] in C57BL/6 mice on day 9 of pregnancy on the hippocampal expression of SNAP-25 in postnatal day 0 neonates, and compared them to sham-infected pups. The expression of SNAP-25 in infected neonates varied along the septotemporal axis of hippocampus and in various anatomic layers. Quantitative densitometric analysis of specific immunogold silver-enhanced SNAP-25 immunoreactivity [IR] showed increases of 40-347% over control in all septal-dorsal hippocampal layers except for the subplate layer. In mid septo-temporal hippocampus, SNAP-25 IR increased by 10-114% over control in all layers, except for the hippocampal plate, but the extent of this increase was smaller than in the dorsal-septal area. Finally,in temporal-ventral levels, SNAP-25 expression was reduced in all infected layers by 21-33% below control except for mild increases of 8.8 and 10% in subplate and hippocampal plate layers. Additionally, the infected SNAP-25 maximal density bin shifted to lower values dorsally and to higher values medially, with ventral maximal bins remaining unchanged when compared to controls. The differential expression of SNAP-25 in the hippocampi of infected neonates indicates a variable degree of vulnerability across the septo-temporal axis of hippocampus. It is surmised that while viral infection may induce excitotoxicity in the ventral hippocampus, it may cause reactive synapto-genesis in the medial and dorsal sectors of the developing brains of postnatal day 0 neonates.

Animals↗
PubMed1996

Rat eosinophils: isolation and characterization of superoxide production.

Studies with isolated cells are important to the understanding of mechanisms by which eosinophils participate in allergic inflammation. Due to species variability, isolation techniques and cell biology need to be defined for each source. We developed methods to obtain rat eosinophils with purity and viability exceeding 90%, characterized the superoxide anion production of these cells in response to standard activators, and compared these results with those previously obtained in our laboratories with the use of human eosinophils. Rat eosinophils responded vigorously to phorbol myristate acetate and poorly to platelet-activating factor and to N-formyl-methionyl-leucyl-phenylalanine, parallel to the responses of human eosinophils. In contrast, rat eosinophils responded unlike human eosinophils to other activators, having a larger response to calcium ionophore A23187, a smaller response to serum-treated or serum-opsonized zymosan, and a negative rather than positive modulatory effect of cytochalasin B. We conclude that rat eosinophils can be obtained in high purity and with intact responsiveness to a number of different activators.

Animals↗
PubMed1994

Relationship of plasma epinephrine and circulating eosinophils to nocturnal asthma.

The mechanisms of nighttime airway obstruction are not fully established, but include circadian fluctuations in epinephrine and cortisol. To evaluate the relationship of circadian patterns in epinephrine and cortisol to nighttime airflow obstruction, 10 young adult asthma patients (ages 19 to 25 yr) were admitted to a hospital clinical research unit for a 3-day study during which plasma concentrations of epinephrine, cortisol, and histamine were determined along with white blood cell and eosinophil counts every 6 h (1600, 2200, 0400, and 1000 h). Six of the 10 patients experienced at least one episode of nocturnal asthma (defined by more than a 15% decrease in antemeridian (A.M.) to postmeridian (P.M.) FEV1 values). Plasma epinephrine levels (pg/ml) showed a circadian pattern, and the concentration at 2200 h was significantly (p = 0.039) different for the nocturnal and non-nocturnal asthma groups. Circulating eosinophil numbers were greater in subjects who had more frequent episodes of nocturnal asthma, and correlated with the frequency of nocturnal asthma (r = 0.732, p = 0.02, Spearman rank correlation) and average percent decrease in FEV1 (r = 0.667, p = 0.035). Plasma cortisol concentrations also showed circadian patterns, but no direct association with nocturnal asthma; plasma histamine concentrations showed no circadian patterns and no association with nocturnal asthma. Our findings indicate that changes in plasma epinephrine precede the development of nocturnal airway obstruction and contribute to the likelihood of nighttime airflow obstruction.

Adult↗
PubMed1993

The cost of infection in surgical patients: a case-control study.

To determine the excess hospital cost attributable to hospital acquired infection in a UK hospital 67 surgical patients with hospital acquired infection (HAI) were matched with uninfected controls on the primary features of the first operative procedure and primary diagnosis, and on the secondary features of sex, age and surgical service. Costs were calculated from the hospital's unit costs for pathology, radiology and for the cost of one day's extra stay. The mean cost of one day of antibiotic therapy was also measured. In infected patients there was a significant increase in the length of hospital stay of 8.2 days with a mean extra cost per patient of 1041 pounds (P < 0.001). Microbiology, haematology, chemical pathology and radiology requests were all significantly increased with a mean extra cost per infected patient of 10.4 pounds, 7.8 pounds, 96. pounds, and 3.3 pounds, respectively. Antibiotic therapy contributed significantly to the extra costs (44 pounds per infected patient). The mean extra cost per patient was highest in orthopaedic patients (2646 pounds) and least in gynaecology patients (404 pounds). For the infections with significantly increased cost, multiple infections carried the greatest (3362 pounds), and urinary tract infections the least (467 pounds) cost. Hospital length of stay was the greatest contributor to the cost and accounted for 95% of the extra cost in orthopaedics, 94% in gynaecology and 92% in general surgery and urology. Antibiotic therapy was the second most significant contributor to cost and, with the exception of urinary tract infection and infections in gynaecology, was at least five times more per patient than requests for microbiology, haematology, chemical pathology or radiology.

Case-Control Studies↗
PubMed1992

Augmentation of major histocompatibility complex class I and ICAM-1 expression on glial cells following measles virus infection: evidence for the role of type-1 interferon.

An intracellular staining procedure for the cytoskeletal marker, glial fibrillary acidic protein of astrocytes, has been developed which allows flow cytometric phenotyping of astrocytes within complex mixtures of glial cells. Employing this technique, we show here that measles virus infection of rat mixed glial cell cultures results in a rapid augmentation of major histocompatibility complex (MHC) class I and ICAM-1 on the majority of astrocytes in culture. MHC class I levels are increased on macrophages/microglia but ICAM-1 expression is not normally affected on this cell type. Some MHC class II induction is also observed after virus infection but only on astrocytes. A type-I interferon (IFN)-inducible protein, Mx, was identified in cultured glial cells after infection. Qualitatively comparable MHC class I and ICAM-1 enhancement after addition of type-I IFN, supports the conclusion that this cytokine(s) released as a result of virus infection, is responsible for alterations in the expression of molecules on glial cells, that are involved in T cell recognition. Astrocytes after viral infection were more susceptible to alloantigen-specific cytotoxic T lymphocytes and cytotoxic T lymphocyte activity was substantially reduced in the presence of mAb specific for MHC class I, ICAM-1 and LFA-1 but not MHC class II. The relevance of these findings to T cell recognition of virus-infected cells in the central nervous system is discussed.

Animals↗
PubMed1992

Anaesthetic management of renin secreting nephroblastoma.

We report the successful preoperative control and anaesthetic management of severe hypertension in a 7-month-old baby with nephroblastoma and increased renin activity. The strategy for selection of appropriate antihypertensive pharmacological agents and the anaesthetic implications and management of the condition are discussed.

Anesthesia↗
PubMed1991

Nucleocapsid or spike protein-specific CD4+ T lymphocytes protect against coronavirus-induced encephalomyelitis in the absence of CD8+ T cells.

To investigate the antiviral CD4+ T cell response in coronavirus MHV-JHM-induced encephalomyelitis, spleen and thymic lymphocytes from diseased rats were stimulated in culture with virus Ag, expanded and tested for their specificity to viral proteins and nucleocapsid (N) and spike (S) proteins that had been expressed in bacteria. A strong T cell response specific for N was measurable during acute disease, whereas S-specific T cells were only detectable in rats with a later onset of disease. CD4+ T cell lines with specificity for virus and either N or S protein were established and their influence on the course of a mouse hepatitis virus-JHM infection was investigated. All lines were of the CD4+ phenotype. Both N and S protein-specific CD4+ T cells conferred protection to infected Lewis rats and reduced the amount of infectious virus in the central nervous system. After transfer of CD4+ T cells and challenge with virus, an increase in the antiviral IgM response occurred, but neutralizing antibodies were not detectable during the period of virus clearance. Previous CD8+ cell depletion did not abrogate protection mediated by CD4+ T cell line transfer.

Animals↗
PubMed1991

An assessment of selective surveillance methods for detecting hospital-acquired infection.

Three selective surveillance methods were compared to a reference method in their ability to detect hospital-acquired infection (HAI) in patients occupying 122 beds of a district general hospital. The time for data collection was also assessed. The selective methods consisted of: (a) ward liaison surveillance (WLS), conferring with nursing staff twice weekly to determine patients with infections; (b) risk factor surveillance (RFS), the follow-up of patients with "clues" that indicated a risk of infection; and (c) laboratory-based ward liaison surveillance (LBWLS), the follow-up of positive microbiology reports by reviewing case records, in addition to conferring with nursing staff. The reference method consisted of total continuous clinical surveillance and the review of laboratory reports. During the 11-month period of the study, the reference method identified 306 HAI in 3,326 patients. LBWLS identified 71%, WLS 58%, and RFS 49% of HAI. The time for data collection (per week) was 7.75 hours for LBWLS, 4.3 hours for WLS, and 7.9 for RFS. In the United Kingdom, LBWLS was concluded to be an effective method of surveillance.

Cross Infection↗
PubMed1991

Interhospital transfer of a patient undergoing extracorporeal carbon dioxide removal.

Extracorporeal circulation techniques are being used increasingly in patients with acute cardiac or pulmonary failure. Some of these patients may subsequently require transportation, which has limited the use of these techniques in hospitals without on site transplantation facilities. We report a case of adult respiratory distress syndrome that demonstrates a solution to this problem.

Adolescent↗
PubMed1991

The role of eosinophils in the pathophysiology of asthma.

From current information, a number of conclusions can be drawn. Antigen activation of the allergic reaction in the airways is associated with an immediate rise in mast cell derived mediators, including histamine and tryptase. Associated with antigen activation of the allergic reaction is recruitment of eosinophils to the airways. This can best be seen in the airway lavage 48 hours after challenge with antigen. An increased presence of eosinophils suggests that they are an important contributor to the late allergic reaction and may be one of the major constituents in the development of bronchial inflammation. Although many factors participate in the late allergic inflammatory response, eosinophil-derived proteins are known to cause airway injury. Regulation of eosinophils in this process is not clearly established; however, our findings of increased IL-5 in relationship to the presence of eosinophils and their granular proteins suggests that this cytokine may be an important modulator of eosinophil function and activation following allergen challenge. However, much remains unknown in understanding bronchial inflammation and the eosinophil's role in the process. In conclusion, the eosinophil is a major cellular participant in late phase allergic airway disease. Its presence and known functions suggest that the eosinophil is a significant cellular factor in the development of allergic airways disease in asthma. Further advances in this area will follow continued studies, particularly those which involve biopsy and correlation with airway physiology.

Animals↗
PubMed1990

Astrocytes as antigen presenting cells for primary and secondary T cell responses: effect of astrocyte infection by murine hepatitis virus.

CD4+ T cell lines specific for murine hepatitis virus (MHV) - JHM or myelin basic protein (MBP) proliferated when cultured together with MHC class I and II positive syngeneic rat astrocytes and either inactivated virus or MBP as antigen. The magnitude of the T cell proliferative response was comparable to that seen when thymocytes were used as a source of antigen presenting cells (APC). In contrast, MHC class I and II positive astrocytes were unable to significantly stimulate the proliferation of highly purified populations of naive CD4+ and CD8+ T cells in an allogeneic mixed lymphocyte reaction (MLR). Both T cell populations proliferated when mixed with allogeneic lymph node cells. Infection of the astrocytes with a variant of MHV-JHM (PI-AS22D) did not alter this cells incapacity to stimulate the naive CD4+ and CD8+ T cells to proliferate.

Animals↗
PubMed1990

Post-operative urinary tract infection and wound infection in women undergoing caesarean section: a comparison of two study periods in 1985 and 1987.

In 1985 and 1987 women undergoing Caesarean section were studied for the development of post-catheterization bacteriuria, urinary tract infection and wound infection. In 1985, 34% developed bacteriuria compared to 25% in 1987. Post-catheterization bacteriuria within two days was reduced by improved catheterization techniques. Late urinary tract infection after 5 days occurred in 2% of women in 1985 and 6% in 1987. The commonest bacteria were Escherichia coli and enterococci. Post-catheterization bacteriuria was only confirmed in a second urine specimen in 53%. The incidence of wound infection was 20% in 1985 and 15.8% in 1987 but bacterial pathogens were only isolated from 12.5% and 5.1% respectively. Staphylococcus aureus was isolated in 60% of infected women. Antimicrobial usage was high in this group of women at 41% in 1985 and 27% in 1987. A significant reduction of usage from 37% to 16% was seen in bacteriologically confirmed infections where the laboratory reports were only issued after examination of a second specimen. However most symptomatic women received treatment. The incidence of post-operative infective complications is high in women having Caesarean section. Careful urethral catheterization techniques are necessary to prevent bacteriuria.

Adolescent↗
PubMed1989

The effect of azelastine on neutrophil and eosinophil generation of superoxide.

Azelastine is a new investigational drug used to treat rhinitis and asthma. In addition to described actions that include inhibition of immunologic release of histamine from mast cells and basophils, blockade of smooth muscle contraction to various spasmogenic mediators, and relaxation of airway smooth muscle, azelastine has been ascribed anti-inflammatory properties. To understand further the mechanisms by which azelastine may regulate inflammation, its effect on neutrophil and eosinophil superoxide (O2-) generation was evaluated. Purified suspension of neutrophils (greater than 95% pure) and eosinophils (greater than 85% pure) were isolated from human peripheral blood samples by continuous density gradients of Percoll. The isolated granulocyte suspensions (1 x 10(5) cells) were added to 96-well microtiter plates in the presence of cytochrome c, activated by either N-formyl-methionyl-leucyl-phenylalanine, phorbol myristate acetate, calcium ionophore A23187, or opsonized zymosan particles; O2- generation was measured by the reduction of cytochrome c. We found that azelastine significantly inhibited both neutrophil and eosinophil generation of O2- in a dose-dependent fashion (10(-7) to 10(-5) mol/L) with each activator except zymosan. Furthermore, the degree to which azelastine suppressed O2- was similar in neutrophils and eosinophils. Thus, azelastine, in concentrations achieved therapeutically, inhibited granulocyte generation of O2-. This anti-inflammatory effect may also be beneficial in the treatment of asthma.

Adult↗
PubMed1989

Lymphocyte-myelin sheath interactions in acute experimental allergic encephalomyelitis.

Using a passively transferred acute model of experimental allergic encephalomyelitis (EAE) in the rat, inflammatory central nervous system (CNS) lesions were shown to develop rapidly, peak and then resolve. An unusual feature of the lesions in the CNS was the presence of pyknotic cells within myelin sheaths. A sequence of observations indicated that such cells were lymphocytes which had insinuated themselves into the myelin sheath by passage along the interperiod line. The presence of lymphocytes within myelin sheaths, a process which did not lead to demyelination, was considered to represent a change which reflects the specificity of the immune response in this disease. The detection of this change in other CNS autoimmune diseases, notably those associated with virus infections, may be important as an indicator of pathogenetically relevant lymphocyte-myelin interactions.

Acute Disease↗
PubMed1989

Antigen presentation in brain: brain endothelial cells are poor stimulators of T-cell proliferation.

The capacity of rat brain capillary endothelium to present antigen to primed peripheral lymph node cells or to ovalbumin-specific T-cell lines was examined in vitro. Brain endothelium can present antigen, but it is generally ineffective at stimulating T-cell division. Division is only seen when indomethacin is included in the cultures to suppress eicosanoid production. Even under these conditions an endothelial monolayer is only 1/40 as effective as a thymocyte monolayer in stimulating division. The failure to act as an effective antigen presenting tissue is not due to lack of IL-1 production, nor is it related to the extended time required to induce MHC class II molecules on these cells. In the presence of high levels of antigen-specific T cells, the endothelium appears to be subject to cytotoxic damage, so that T-cell stimulation is lowest with higher numbers of T cells--the opposite of that seen with conventional antigen-presenting cells. These findings support the view that brain endothelial cells are not important in stimulating T-cell division during the development of immune reactions in brain, although these cells may be recognizable by class II-restricted cytotoxic cells.

Animals↗
PubMed1988

Anaphylaxis following "Hexabrix" during routine coronary angiography.

A case is described of an anaphylactic reaction to "Hexabrix 320" radiographic contrast medium in a patient undergoing routine coronary angiography. The case is reported because such reactions to "Hexabrix" are considered rare, because the patient was pretreated with hydrocortisone and chlorpheniramine, and because of the continuous monitoring that occurred during the procedure.

Aged↗
PubMed1987

Experimental allergic encephalomyelitis in the absence of a classical delayed-type hypersensitivity reaction. Severe paralytic disease correlates with the presence of interleukin 2 receptor-positive cells infiltrating the central nervous system.

One characteristic of experimental allergic encephalomyelitis (EAE) in all species is the presence of a considerable leukocyte infiltrate in the central nervous system (CNS). By adoptive transfer of EAE into irradiated or nonirradiated Lewis strain rats we now show that the bulk (greater than 90%) of infiltrating cells in the CNS are superfluous to the induction of disease, as lethally irradiated recipients, despite having very few infiltrating cells in the CNS, acquire severe paralytic EAE. The reduction in the level of infiltration in irradiated recipients is selective, however, as both irradiated and nonirradiated diseased animals have very similar numbers of cells expressing IL-2-R. Disease in irradiated recipient animals is associated with substantial submeningeal hemorrhage in the spinal cord and brain stem and similar hemorrhages are found in recipients rendered leukopenic with cytotoxic drugs. Clinical signs of disease and hemorrhage are preventable, however, by administration to the recipient rats of mAbs specific for the CD4 antigen. Classic delayed-type hypersensitivity (DTH) reactions are transferable with the same cells that produce EAE in both irradiated and nonirradiated recipient rats, but such transfer of DTH is observed only in nonirradiated recipient animals and not in irradiated rats. Collectively, the findings reported herein support the conclusion that the paralysis characteristic of acute EAE is mediated by the direct action of very small numbers of activated CD4+ lymphocytes that infiltrate the CNS and produce their effects by inducing vascular damage. The findings are not consistent with reports that the lesions in EAE are produced by a classic DTH reaction.

Animals↗