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Biomedical subjects

W S Walker

Publications and source records attributed to W S Walker.

At least 37 records · Page 2Linked to original sources
PubMed1998

Mouse resident microglia: isolation and characterization of immunoregulatory properties with naïve CD4+ and CD8+ T-cells.

We describe a non-enzymatic procedure designed to isolate in high purity resident microglia from the brains of normal mice. This procedure allowed for the characterization of the cells without concern that their surface features had been enzymatically altered during tissue processing. A cell population was obtained and judged to consist primarily of microglia because essentially all the cells were Mac-1+, Mac-3+, F4/80+, CD44+, CD54+, and CD86+, and they expressed CD45 with a mean fluorescence intensity value of about one-half that of tissue macrophages. The cells also expressed marginal levels of MHC class I, CD14, CD40, and CD80, but lacked detectable MHC class II, CD4, CD8, CD45R, and CD102 molecules. Molecular phenotyping revealed that the purified microglial population contained mRNA transcripts encoding the receptor for colony stimulating factor-1 (CSF-1), the macrophage growth factor, and contained few, if any, transcripts for glial fibrillary acidic protein, an astrocyte-specific marker. Ex vivo, the microglia constitutively stimulated, in the mixed leukocyte reaction, the proliferation of naive allogeneic CD8+, but not CD4+ T-cells. However, they failed to present a protein antigen to naive antigen-specific CD4+ T-cells unless pretreated with interferon-gamma, a response that was inhibited by antibodies to CD86. Agar-cloning experiments confirmed that normal mouse brain contains a CSF-1-responsive cell that gave rise to cells with identical immunophenotypic characteristics as freshly isolated resident microglia. Moreover, the microglial progenitor cell located in a density fraction that was different from that containing the mature resident microglia.

Animals↗
PubMed1997

HEL-Flu: an influenza virus containing the hen egg lysozyme epitope recognized by CD4+ T cells from mice transgenic for an alphabeta TCR.

Reverse genetics was used to modify the influenza virus genome by inserting the p46-63 sequence of hen egg lysozyme (HEL) into the neuraminidase stalk of the virus. The resulting virus, HEL-Flu, contained the epitopes recognized by CD4+ T cells from 3A9-TCR transgenic mice (C3HTg). Here, we show that HEL-Flu was infectious in the respiratory tract of both C3H and C3HTg mice, the latter animals showing an early, transient morbidity. Splenic dendritic cells and certain cloned populations of splenic macrophages and brain microglia constitutively presented infectious and inactivated HEL-Flu to the T cells in an Ag-specific and MHC class II-restricted manner. These results demonstrate the utility of HEL-Flu in assessing the APC activity for naive T cells; they also extend the previous studies showing that discrete populations of macrophages and microglia constitutively process and present Ag to naive T cells.

Animals↗
PubMed1997

Expression of chemokine genes in rat glial cells: the effect of myelin basic protein-reactive encephalitogenic T cells.

Chemokine gene expression and chemokine activity appear to be major components of the immunopathological processes of inflammation and autoimmunity. To initiate an investigation of the role of chemokines in the pathogenesis of autoimmune inflammatory demyelination, we examined the expression of mRNA transcripts encoding four prominent chemokines, IP-10, MIP-1 alpha, MCP-1, and RANTES, in encephalitogenic rat MBP-reactive T cells, astrocytes, and microglia. Astrocytes and microglia, whether as lines or as freshly isolated cells, did not constitutively express IP-10 and MCP-1 mRNA but could be induced with LPS to also produce MIP-1 alpha and RANTES. MBP-reactive T cells were induced with MBP to produce abundant levels of MIP-1 alpha, MCP-1, and RANTES mRNA in different temporal profiles but did not express IP-10 mRNA. In an MHC-II restricted fashion, the antigen-activated MBP-reactive T cells also induced glial cells to express all four chemokines, with the chemokine gene expression greatest following T-cell interactions with MHC-compatible glia. Treatment of glial cells with TNF-alpha and IFN-gamma induced only IP-10, indicating that the expression of chemokine genes other than IP-10 requires a combination of different cytokines or direct cell-cell contact between T cells and glia. Quantitative assays revealed that activated astrocytes, the dominant glia of the CNS, express higher levels of chemokine transcripts than transcripts of the major proinflammatory cytokines TNF-alpha and IFN-gamma. These results underscore the prominent but complex expression of chemokines by cellular component of inflammatory demyelinating lesions.

Animals↗
PubMed1997

Prediction of requirement for, and outcome of, prolonged mechanical ventilation following cardiac surgery.

The prediction of requirement for, and short- and long-term outcome of, prolonged mechanical ventilation after cardiac surgery is ill-defined. The aims of this study were to isolate any predictive indices which might identify those groups of patients who may require prolonged ventilation postoperatively and to determine which factors significantly affect outcome in the prolonged-ventilation group. Following case note review of 139 consecutive cardiac surgical patients ventilated for > or = 7 days following surgery, 43 factors were recorded on each patient, including smoking, pulmonary function, chest infection, and chronic obstructive airways disease. Of 139 patients, 89 were discharged from hospital (64% survival); of these, 52 were alive at long-term follow-up (58% long-term survival). Statistical analysis identified urban residence, chronic obstructive airways disease, prolonged operation, and bypass time as significant predictors of requirement for prolonged ventilation postoperatively. On multivariate analysis five factors were predictive of increased intensive care mortality, including urban residence, inotrope days, sepsis, perioperative cerebrovascular accident and coagulopathy requiring fresh frozen plasma transfusion postoperatively. Following discharge from hospital, four factors were found to be significant predictors of increased mortality: these are impaired preoperative ejection fraction, increasing age, impaired preoperative pulmonary function, and abscence of preoperative aspirin medication. These factors should be considered in intensive care planning, long-term follow-up and importantly on clinical decision making in the individual patient.

Adult↗
PubMed1997

Pleurocutaneous fistula as a complication of radiation treatment in locally advanced breast cancer.

We report the first case of a pleurocutaneous fistula as a consequence of megavoltage radiation therapy for a recurrent locally advanced breast cancer. Several factors, such as previous surgery, blood supply, fraction size, and perhaps increased radiosensitivity, which influence the tolerance of the late reacting normal tissues to radiotherapy, may have predisposed our patient to this rare complication.

Adenocarcinoma, Scirrhous↗
PubMed1997

A proposed anatomical classification of the pulmonary fissures.

No method of classifying pulmonary fissures currently exists, however, the nature of the fissure is of great importance in planning operative strategy for thoracoscopic pulmonary resection where an incomplete fissure may contribute to post-operative air leakage. In order to provide a framework for description of operative technique and to allow meaningful comparison between different surgical series, we propose a fissural classification based on both the degree of completeness of the fissures and the location of the pulmonary artery at the base of the oblique fissure. Completeness of a fissure is graded in four stages: grade 1--complete fissure with entirely separate lobes; grade 2--complete visceral cleft but parenchymal fusion at the base of the fissure; grade 3--visceral cleft evident for part of the fissure; grade 4--complete fusion of the lobes with no evident fissural line. The relationship of the pulmonary artery to the oblique fissure is described by the term 'fissural balance'. The pulmonary artery lies centrally to the oblique fissure in a 'normally balanced' fissure. Anterior or posterior displacement of the artery is referred to as anterior or posterior 'imbalance'.

Endoscopy↗
PubMed1996

Alloantigen presentation to naive CD8+ T cells by mouse microglia: evidence for a distinct phenotype based on expression of surface-associated and soluble costimulatory molecules.

We previously showed that approximately one-third of mouse primary microglial clones derived from individual precursor cells residing in normal brain constitutively present alloantigens (alloAgs) to naive CD8+ T cells (Moore et al.: J Neuroimmunol 41:203, 1992). To understand the basis for this alloAg presenting (alloAgP) activity, we developed a panel of microglial cell lines that were characterized by patterns of alloAgP activity similar to that of the primary clones. Flow cytometric analysis revealed that microglia with and without alloAgP activity expressed similar levels of major histocompatibility complex class I molecules; however, CD80 (B7-1) and CD86 (B7-2) expression was primarily restricted to the alloAgP- cell lines. Monoclonal antibody (Mab) to CD80 only partially blocked the proliferative response of allogeneic CD8+ T cells cocultured with the presenting cell lines, whereas Mab to CD86 completely inhibited the response, indicating a significant role for this molecule in T-cell activation. Using an immunoassay, recombinant mouse cytokines, cytokine-specific Mabs, and the reverse transcriptase-polymerase chain reaction to detect specific cytokine mRNAs, we found the synthesis of interleukin (IL)-1 alpha, IL-6, IL-12, and tumor necrosis factor-alpha (TNF-alpha) to be restricted to the alloAgP- cell lines. Costimulatory roles were then identified for these molecules. We conclude that the ability to present alloAg is a property of a subset of microglia that constitutively express CD86 and secrete costimulatory cytokines that promote the expansion of the alloAg-stimulated CD8+ T cells.

Animals↗
PubMed1996

Oesophagogastrectomy for iatrogenic perforation of oesophageal and cardia carcinoma.

A casenote review identified 18 patients with carcinoma of the oesophagus and gastric cardia who underwent transthoracic oesophagectomy after instrumental perforation. Oesophagectomy was performed within 48 h in ten patients (early surgery group) and after a median delay of 22 (range 5-48) days in eight patients (delayed surgery group). All patients underwent resection via left thoracolaparotomy with immediate intrathoracic anastomosis using the stomach in 17 of 18 patients. There were no anastomotic leaks. Significant postoperative complications occurred in five of ten of the early group with two in-hospital deaths and a mean survival of 551 days. Six of eight patients in the delayed group developed postoperative complications with two in-hospital deaths and a mean survival of 297 days. Transthoracic resection with immediate intrathoracic anastomosis can be performed without anastomotic leakage but there is high associated respiratory morbidity. The timing of oesophagectomy has little effect on hospital morbidity or mortality rates but early surgery is associated with better long-term survival.

Adenocarcinoma↗
PubMed1996

Arachidonic acid activation of monocyte and neutrophil reactive oxygen in lung cancer patients undergoing pulmonary resection.

Reactive oxygen intermediate (roi) generation was investigated in phagocytes of 39 patients undergoing pulmonary resection for lung cancer and 39 paired healthy controls. Generation of roi in monocytes and neutrophils was monitored using 2',7'-dichlorofluorescin diacetate. Activation associated with hydrophobic interactions was probed by analysis of phagocyte roi activation by arachidonic acid and gamma-linolenic acid. Patient roi was measured pre-operatively and 2 and 7 days post-operatively. Elevated (P < 0.01) roi production was detected in neutrophils of lung cancer patients. Surgery was associated with an increase (P < 0.05-P < 0.01) in phagocyte roi at 2 and 7 days post-op. Phagocyte roi was stimulated by arachidonic acid and gamma-linolenic acid (1-40 microM) both pre- and post-operatively. Differences in arachidonic acid and gamma-linolenic acid stimulation between patient and control and pre- and post-op patient phagocytes suggest arachidonic acid involvement in phagocyte activation during reactive responses to lung carcinoma and surgery.

Arachidonic Acid↗
PubMed1996

Esophagectomy for carcinoma in the octogenarian.

BACKGROUND: Esophageal carcinoma is predominantly a disease of the elderly, a group often only considered for palliative therapies. METHODS: A case note review identified 31 octogenarians undergoing resection for carcinoma of the esophagus or gastric cardia over a 12-year period ending December 1994. RESULTS: Nineteen patients made either an uncomplicated postoperative recovery (n = 12) or suffered minor complications (n = 7). Of the 12 patients who suffered moderate or severe complications, 5 died (in-hospital mortality, 16%). The deaths included 2 of 3 patients who underwent emergency operation for esophageal perforation and 3 of 28 patients who underwent elective esophagectomy (elective mortality rate, 10.7%). Nineteen of the 26 survivors (73%) experienced no further dysphagia. The 5-year survival rate was 17%. CONCLUSIONS: Elective esophageal resection can be performed safety in selected octogenarians who have no or few coexisting medical problems and present with a localized carcinoma that is technically easy to resect. Patients undergoing emergency operations or in whom moderate or severe postoperative complications develop often have poor physiologic reserve and are therefore at risk of early postoperative death.

Adenocarcinoma↗
PubMed1996

Video-assisted thoracoscopic pulmonary surgery--current status and potential evolution.

The current status of video-assisted thoracoscopic surgery (VATS) of the lung has been reviewed. The published data support the view that VATS pulmonary surgery is feasible and safe. It is associated with decreased perioperative pain and opiate requirement, better postoperative pulmonary function, and probable overall neutral cost impact. A VATS approach is functionally superior to open thoracotomy for wedge resection, pneumothorax surgery and bullous lung disease and may allow surgical intervention in patients with pulmonary function which is in adequate for open resection. Major VATS pulmonary resection with lobectomy and pneumonectomy can be performed for early malignant disease without compromising established surgical principles. Specific training is needed in VATS surgery and background skills in general thoracic surgery are necessary to underwrite major interventions. Decreased cytokine activation and enhanced post surgical immune function may prove to be long-term benefits of VATS surgery.

Endoscopy↗
PubMed1996

A prospective randomized study comparing stapled with handsewn oesophagogastric anastomoses.

One hundred patients with carcinoma of the distal oesophagus or gastric cardia undergoing oesophagogastrectomy were randomized to receive either a stapled or handsewn oesophagogastric anastomosis. Five patients died in the early post-operative period at a mean of 16 days (in-hospital mortality 5%) allowing detailed follow up on the remaining 95 patients who were followed up to death or for a minimum of 36 months. A stapled anastomosis was quicker to perform (P < 0.001), resulting in a shorter operative time (P < 0.005) and was associated with decreased blood loss (P < 0.05). The number of anastomotic leaks, length of in-patient stay, stricture formation and survival in the two groups was not statistically different. A stapled oesophagogastric anastomosis fulfills all of the requirements for routine use in thoracic surgical practice when performing oesophageal resection for carcinoma of the distal oesophagus or gastric cardia. It is quick to perform allowing a shorter operating time and lower blood loss and does not appear to be associated with a previously noted increased incidence of benign anastomotic stricture formation when compared with handsewn anastomoses.

Aged↗
PubMed1996

Oesophagogastrectomy for carcinoma in patients under 50 years of age.

Oesophagogastrectomy for carcinoma of the oesophagus or gastric cardia has been reported as being associated with a poorer outcome in young adults than in older patients in an Oriental population. A retrospective analysis of 597 patients who underwent oesophagogastrectomy for carcinoma was undertaken to ascertain if resection in younger Scottish patients was associated with the same poorer outcome. Forty-seven patients aged less than 50 years were compared with 323 patients aged 50-69 years and 227 patients aged 70 years and older. Young patients had a higher incidence of distal third oesophageal tumours than older patients, who tended to have carcinomas of the gastric cardia. There were no differences with regard to tumour pathology, stage, extent of resection, hospital mortality or survival. In Scotland, carcinoma of the oesophagus or gastric cardia in young adults behaves similarly to that in older patients, and survival following resection is independent of age.

Adult↗