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Biomedical subjects

W S Walker

Publications and source records attributed to W S Walker.

At least 91 records · Page 5Linked to original sources
PubMed1990

Epitope mapping of horseradish peroxidase with use of monoclonal antibodies.

Nine mouse monoclonal antibodies (MAbs) to horseradish peroxidase (HRP) were used to develop an epitope map of the enzyme. The results of a competitive binding assay indicated three distinct patterns of reactivity. Two groups of MAbs (I and III) recognized epitopes located in separate antigenic regions on the molecule; another (II) bound to sites that overlapped with epitopes in either region I or III. Further definition of these regions was obtained by analyzing the MAbs for their binding to isolated heme, other peroxidases and heme-containing proteins, and to denatured and apo-HRP. None of the group I MAbs bound heme, suggesting that this region was removed from the active site of the enzyme. All of the group II and III MAbs bound heme as well as the other peroxidases and heme-containing proteins, indicating that they recognized heme-associated epitopes at or near the active site. Only one MAb (2A2) in groups II and III bound to apo-HRP but not to denatured HRP; it was also the only MAb in the entire panel that inhibited the catalytic activity of HRP. This suggests that the epitope recognized by 2A2 involves both the heme moiety and a conformationally dependent protein determinant near the active site.

Animals↗
PubMed1990

A comparison of cobalt (57Co) bleomycin scanning and contrast-enhanced CT scanning for assessment of the mediastinum in lung cancer.

Sixty patients with histologically proven lung cancer who had been accepted for mediastinoscopy or thoracotomy were prospectively entered into a study to evaluate computed tomographic (CT) scanning, 57Co-bleomycin scanning, and barium swallow in preoperative assessment of mediastinal lymph node metastasis. Fifty-six patients had thoracotomy at which all accessible lymph nodes were sampled. Twenty-four patients were found to have mediastinal tumor on histologic analysis of the resected mediastinal lymph nodes. Neither 57Co-bleomycin scanning nor barium swallow were clinically useful, with sensitivities of 21 percent and 11 percent respectively, whereas CT scanning was helpful. However, there was no clear cutoff point of node size to optimize sensitivity and specificity for CT scanning. When nodes greater than or equal to 15 mm were taken to indicate likely malignancy, the sensitivity was 58 percent and the specificity was 87 percent and when greater than or equal to 10 mm was used the sensitivity was 80 percent but the specificity was only 55 percent. There was no clear relationship between the size of the largest resected lymph node in each patient and the presence of malignant lymph nodes. Only 42 percent of patients with resected nodes greater than or equal to 2 cm had histologic evidence of metastases. We conclude that CT scanning should be used to indicate the presence and site of mediastinal lymph nodes, which, when visualized, should always be sampled and histologically examined prior to resection of primary tumor.

Aged↗
PubMed1990

Role of mediastinoscopy in the diagnosis of mediastinal masses.

In order to assess the diagnostic efficiency of mediastinoscopy in patients with undiagnosed mediastinal masses, a retrospective review was undertaken of the results obtained in a consecutive series of 42 patients presenting over a 5-year period. In 28 (67%) patients, a tissue diagnosis was made. Ten (24%) patients underwent a negative mediastinoscopy but were found to have significant pathology on further investigation (eight in a location outside the range of conventional mediastinoscopy). Four (10%) patients had negative findings and were confirmed to have no significant pathology on further investigation and follow-up. Overall, mediastinoscopy had a sensitivity of 74%, a specificity of 100% and an accuracy of 76%; however, for lesions within the range of mediastinoscopy, the sensitivity was 93%, the specificity 100% and the accuracy 94%. The predictive value of a negative examination was 66%. Mediastinoscopy is a valuable technique in the diagnosis of mediastinal masses but, because of the low predictive value of a negative examination, further evaluation, including thoracotomy if necessary, is still indicated if mediastinoscopy is unhelpful.

Adolescent↗
PubMed1989

Differential antigen presentation by cloned populations of mouse splenic macrophages.

Soft agar colonies of mouse splenic macrophages differ in their ability to process and present complex Ag to T cell hybridomas. To determine if the basis for this differential activity was the synthesis of molecules that might interfere with the activity of either the hybridoma or the indicator cells used for the bioassay of IL-2, culture supernatants were compared from Ag-presenting and nonpresenting cultures for their content of suppressor activity, using mitogen-treated mouse SC. No correlation was found between a colony's Ag-presenting activity and its secretion of suppressor factors, nor did colonies unable to present Ag release factors that interfered with the detection of IL-2. In a second approach, paired subcultures from individual colonies were tested for their ability to present, to the same hybridoma, both native Ag and the "preprocessed" peptide of the Ag. The presentation of native Ag was restricted to the progeny of a minority of the cloned macrophage progenitors, but all of the progeny cultures presented the peptide. Together, these results suggest that the basis for differential Ag presentation may be in the manner in which the cloned macrophages degrade and process ingested Ag.

Animals↗
PubMed1989

Percutaneous cricothyroidostomy (minitracheostomy) for bronchial toilet: results of therapeutic and prophylactic use.

In the period 1984 to 1988, 2,448 patients underwent major thoracic operations in our unit. Of these patients, 144 (5.9%) underwent percutaneous cricothyroidostomy (minitracheostomy) using a 20F pediatric silver tracheostomy tube. Minitracheostomies were performed for the treatment of sputum retention in 81 patients, prophylactically in 62 patients, and as a route for high-frequency jet ventilation in 1 patient. Minitracheostomy tubes remained in situ a median of four days. Suction function was satisfactory in 99% of patients, with only 2 patients requiring subsequent suction bronchoscopy and no occurrence of tube blockage. Ninety-four percent of minitracheostomies performed were entirely uneventful. Bleeding was the most common complication (3.5%), and no instances of subglottic stenosis have occurred. During the review period, there was a significant increase in the percentage of patients requiring major operations undergoing prophylactic, but not therapeutic, minitracheostomy (p less than 0.001). This was associated with a significant decrease in the percentage of patients requiring suction bronchoscopy (p less than 0.001). We conclude that prophylactic minitracheostomy with the 20F pediatric silver tracheostomy tube is a safe and effective procedure in the prevention of postoperative sputum retention.

Aged↗
PubMed1989

Comparison of ventricular septal surgery and mitral valve replacement for hypertrophic obstructive cardiomyopathy.

We have reviewed the results of two different forms of surgical management of hypertrophic obstructive cardiomyopathy refractory to medical therapy. Twenty-one patients were treated with 22 procedures between 1963 and 1987. Eleven underwent a ventricular septal procedure by myotomy with or without myectomy, and 11 underwent mitral valve replacement (MVR), 1 of whom had previously undergone a ventricular septal procedure. The groups were comparable with respect to severity and duration of symptoms, age range, electrocardiographic features, and hemodynamic changes. Mitral valve replacement produced a greater and more consistent reduction in the left ventricular outflow tract pressure gradient than a ventricular septal procedure (MVR, 68.3 mm Hg preoperatively and 2.5 mm Hg postoperatively; ventricular septal procedure, 60.1 mm Hg preoperatively and 13.4 mm Hg postoperatively). This was associated with better postoperative ventricular configuration in diastole and more apparent loss of midcavity narrowing in systole. Ejection fraction did not fall after a ventricular septal procedure but decreased significantly from a mean of 79% to a mean of 61% after MVR. Similarly, left ventricular end-diastolic pressure remained unchanged after a ventricular septal procedure but fell from a mean of 26.6 mm Hg to 17 mm Hg after MVR. Although both groups experienced a generally satisfactory symptomatic result, this appeared more reliable with MVR. We suggest that MVR offers a more predictable improvement than a ventricular septal procedure and may be the procedure of choice for units with limited experience with ventricular septal procedures.

Adolescent↗
PubMed1989

Long term survival after pulmonary resection for small cell carcinoma of the lung.

A retrospective review was undertaken of the long term survival of 97 patients with histologically proved small cell carcinoma of the lung resected during the 10 years January 1977-December 1986. Twenty seven patients (28%) had stage I disease, 29 (30%) stage II, and 41 (42%) stage III. Patients with stage I and II tumours were managed by resection alone. Patients with stage III disease received adjuvant chemotherapy (cyclophosphamide, doxorubicin, and vincristine). Pneumonectomy was undertaken in 75 patients, lobectomy in 21, and wedge resection in one patient. Three patients died within 30 days of operation. The cumulative five year survival of all patients, irrespective of tumour stage, was 17%. The cumulative five year survival was 35% for patients with stage I disease, 23% for stage II, and zero for stage III. The median survival for patients with stage III tumours was 17 months. There was no significant difference in cumulative survival between patients with stage I and II disease. Cumulative survival, however, was significantly better for patients with stage I and II disease than for those with stage III disease. The data suggest that for patients with stage I and stage II disease surgery offers the prospect of long term survival.

Adult↗
PubMed1988

Immortalization of cloned mouse splenic macrophages with a retrovirus containing the v-raf/mil and v-myc oncogenes.

The recombinant retrovirus J2, which contains the v-raf/mil and v-myc oncogenes, was used to immortalize mouse splenic macrophages that had been cloned in soft agar. When added to freshly harvested colonies, J2 failed to yield cell lines but it immortalized up to 30% of the clones if they had been maintained for at least 4 months in medium containing colony-stimulating factor 1 (CSF-1). All of the cell lines grew in agar in a CSF-1-independent manner, and they produced tumors in nude and syngeneic mice. The cell lines were judged to be macrophage based on morphological criteria and because they secreted lysozyme, were phagocytic for antibody-coated particles, and expressed both the Mac-1 antigen and the CSF-1 receptor. The cell lines could be divided into three groups based on their expression of Ia and their ability to present an antigen to a T-cell hybridoma. The majority of the lines did not constitutively express Ia or present antigen, but a lymphokine did induce Ia in all of the lines, with most of them also acquiring antigen-presenting activity. However, a small proportion of lymphokine-treated lines continued to lack antigen-presenting activity despite their ability to express Ia. The third and smallest group of cell lines constitutively expressed both Ia and antigen-presenting activity. These results show that the J2 recombinant retrovirus is a useful means of immortalizing functionally distinct populations of cloned splenic macrophages.

Animals↗
PubMed1988

In vivo activation of quiescent B cells by anti-immunoglobulin. II. Production of lysozyme-specific monoclonal antibodies of desired isotype.

We wished to determine whether injection of mice with anti-isotype antibody would be a means to regulate in vivo isotype expression and to obtain hybridomas secreting monoclonal antibodies (mAbs) of desired antigen specificity and isotype. Treatment with a rat mAb (7D2) reactive with both the IgG2a and IgG2b isotypes of mouse Ig resulted in large increases in the serum concentrations of mouse IgG2(a + b). Moreover, injection of antigen-7D2 conjugates had a profound effect on the isotype distribution of hybridomas subsequently obtained from these animals. Thus, while greater than 95% of anti-hen eggwhite lysozyme (HEL) mAbs prepared from mice immunized with HEL alone were of the IgG1 isotype, 12/15 (80%) of the mAbs from mice injected with HEL-7D2 conjugates were of the IgG2a or IgG2b isotype. When tested for effector functions using HEL-coated erythrocytes, the mAbs showed the expected activities, i.e., the IgG2, but not IgG1 anti-HEL mAbs were able to fix complement, bind protein A, and mediate antibody-dependent cytotoxicity and phagocytosis. These results indicate that in vivo immunization with anti-isotype-antigen conjugates can be used to produce hybridomas of predetermined antigen and isotype specificities.

Animals↗
PubMed1988

Post-transfusion purpura following open heart surgery: management by high dose intravenous immunoglobulin infusion.

We present three cases of post-transfusion purpura (PTP) developing in the immediate post operative period after open heart surgery. All had developed platelet specific antibodies and severe anaphylactoid reactions occurred to platelet transfusion in two cases. Treatment with high dose intravenous immunoglobulin (IV IgG) led to complete recovery in two patients one of whom demonstrated a marked biphasic response pattern to therapy. The other died from congestive cardiac failure. PTP is a potentially fatal complication which may well become more frequent with increasing blood product usage.

Aged↗
PubMed1988

Macrophage cell cycling: influence of proliferative state on the antibody-mediated activities of rat resident peritoneal macrophages.

Countercurrent centrifugal elutriation (CCE) was used to isolate fractions of rat resident peritoneal macrophages that were enriched in different phases of the cell cycle. The purpose was to assess the influence of the proliferative status of these cells on their antibody-mediated phagocytic activity. Autoradiographic analysis of the resident peritoneal cell population isolated 1 hr after an intravenous injection of [3H] thymidine showed that about 3% of the macrophages were in S-phase of the cell cycle. CCE yielded fractions of macrophages in which the proportions of S-phase cells ranged from 0% to about 10%. Results of flow cytometric analysis of propidium iodine-stained cells were consistent with the autoradiographic findings. Essentially all of the macrophages in the CCE fractions ingested antibody-coated particles, but there were marked differences in phagocytic capacity and in expression of Fc-receptors among discrete groups of cells. CCE fractions with the smallest cells and no S-phase macrophages ingested approximately six- to eightfold fewer particles than did macrophages from CCE fractions with the largest cells and enriched in S-phase macrophages. Similarly, smaller macrophages bound fewer antibody-coated particles than did larger macrophages. These results, which are identical to those previously reported for murine macrophage cell lines, show that the number of Fc-receptors and the phagocytic capacity of cycling resident peritoneal macrophages increase as the cells progress from G1 to G2. Thus, the proliferative state of macrophages does not determine whether they are phagocytic but rather their phagocytic capacity.

Animals↗
PubMed1988

Simplified peroperative placement of temporary right atrial pacing leads.

A simple technique for securing right atrial pacing leads is described. The method relies on pressure fixation by haemostatic clips. Clinical experience over a 2 year period has demonstrated that this system provides safe, reliable and rapid lead attachment. No problems with lead removal have been encountered.

Cardiac Pacing, Artificial↗
PubMed1988

High-dose folinic acid and 5-fluorouracil in the treatment of advanced colon cancer.

Forty-eight patients with measurable metastatic colorectal cancer were treated with leucovorin (FA), 80 mg/m2 as an intravenous (i.v.) infusion over 20 h, followed by 5-fluorouracil (5-FU), 400 mg/m2, i.v. push on days 1-3. This same dose of FA was then administered as a 1-h infusion on day 11 and weekly thereafter, followed by 5-FU, 400 mg/m2, slow intravenous (i.v.) push. Thirty patients had received no prior chemotherapy, and 18 patients had received chemotherapy with various other regimens. The drugs were well tolerated, with minimal hematologic toxicity and mild to moderate gastrointestinal and mucosal toxicity. Three complete responses (CRs) and nine partial responses (PRs) were observed. Nineteen additional patients remained stable for prolonged periods of time, and 12 patients continued to progress through treatment. The median survival for responders was 52.5 weeks. The patients who had received prior chemotherapy had lower response rates than the previously untreated patients, but responses were seen in both subsets. The CR plus PR rate in previously untreated patients was 30%, with 40% having stabilization of disease. The CR plus PR rate in patients previously treated with other chemotherapy regimens was 19%, with an additional 50% having stabilization of disease. Patients with stable disease appeared to have a clinical benefit similar to that of patients with PR. Toxicity was generally mild and acceptable and consisted mainly of nausea, vomiting, and mucositis. At these dosage levels, diarrhea was not a limiting toxicity. CRs and PRs occurred only in patients with Eastern Cooperative Oncology Group (ECOG) performance status 1 and 2. Carcinoembryonic antigen (CEA) levels generally reflected the type of clinical response and could often predict responders early on in the course of treatment, but did not quantitatively correlate with the degree of response. This regimen has efficacy at least similar to that of standard 5-FU regimens, and appears to have activity as a "salvage therapy" also. The minimal toxicity of this regimen, its convenience for outpatient use, and the relatively low expense as compared with regimens employing a higher dose of FA recommend it for further investigation.

Adenocarcinoma↗
PubMed1988

Surgical management of left ventricular aneurysm and diffuse coronary artery disease: immediate and long term results in patients receiving three or more grafts.

Because little information is available concerning the outcome of surgery for left ventricular aneurysm when multiple concurrent coronary grafts are required, we have reviewed 35 consecutive patients undergoing aneurysm surgery and multiple (greater than or equal to 3) grafts between December 1973 and April 1984. There were 6 operative deaths (17%). All occurred amongst those (16) undergoing LV plication procedures with no deaths amongst those (19) undergoing aneurysm resection (p less than 0.01). Operative mortality was not influenced by preoperative functional status, left ventricular end diastolic pressure, completeness of revascularisation, endarterectomy (13 patients) or whether cold crystalloid cardioplegia or intermittent aortic cross clamp with ventricular fibrillation was used. Overall 5-year actuarial survival was 70% with survival beyond surgery being 84% to 5 years and independent of the type of aneurysm procedure. Of the survivors, 16 were improved by 1-3 functional classes, 3 were unchanged and one was worse. Surgery in this group of patients offers the prospect of good symptomatic improvement and survival figures which at least equal the results of less complex ventricular aneurysm surgery and exceed those reported for medical management.

Adult↗
PubMed1987

Red blood cell homeostasis: recognition of distinct types of damaged homologous red blood cells by a mouse macrophage cell line.

The mouse macrophage (M phi) cell line IC-21 preferentially ingests a subpopulation of homologous red blood cells (MRBC) from normal mice. This subpopulation presumably bears the so-called transfusion lesion, a consequence of damage acquired during the drawing and processing of blood. To determine if all damaged MRBC were recognized by a common receptor site on IC-21 M phi, we prepared suspensions of MRBC damaged in vitro by treatment with tannic acid and compared the phagocytic uptake of these cells with those bearing the transfusion lesion. Trypsin treatment of IC-21 M phi rendered them unable to recognize MRBC bearing the transfusion lesion; but it had no effect on the uptake of tannic acid-damaged MRBC, showing that IC-21 M phi have separate recognition sites for these two populations of damaged MRBC.

Animals↗
PubMed1987

Expression of Ia antigen in colonies of bone-marrow-derived macrophages.

Cells in colonies of culture-derived mouse and rat bone marrow macrophages were examined for membrane Ia antigen to determine if the steady-state expression of the antigen was restricted to macrophages derived from a distinct population of progenitor cells. Multiple subcultures of macrophages derived from single soft-agar colonies were tested for Ia+ cells on three different days of culture. About one-half of the colonies gave rise to subcultures that never contained Ia+ cells, about 40% yielded subcultures that contained some Ia+ cells on at least 2 of the 3 assay days, and about 10% of the colonies produced subcultures that contained Ia-bearing cells on all 3 assay days. Thus, when cultures were assayed at any one time for their content of Ia-bearing cells, the results raised the possibility of phenotypically distinct subpopulations of progenitors. However, sequential analyses of the subcultures revealed the variable expression of Ia on cells from at least one-half of the colonies. We conclude that, under steady-state conditions, the presence of Ia antigen on bone marrow-derived macrophages is not clonally restricted. That a T-cell-derived lymphokine induced Ia antigen on essentially all the cells in most of the colonies of macrophages confirms their potential to express the antigen.

Animals↗
PubMed1987

Origins of macrophage diversity: functional and phenotypic analysis of cloned populations of mouse splenic macrophages.

Soft-agar colonies of mouse splenic macrophages were examined for surface and functional characteristics that might prove useful in studying the origin(s) of macrophage diversity. Flow cytoflurometric analysis revealed that essentially all cells in all of the colonies bore the Mac-1 and Mac-3 antigens. The colonies did not differ appreciably in their phagocytic activity or in their secretion of lysozyme, but did show different patterns of Mac-2 antigen expression. In most colonies, the cells expressed low levels of the antigen, and in the remainder they expressed a high or an intermediate level of Mac-2. The colonies also differed in their ability to present keyhole limpet hemocyanin (KLH) to an antigen-specific H-2-restricted T-cell hybridoma. About 6% of the colonies gave rise to subcultures with antigen-presenting activity. This presentation was always associated with subcultures containing a high proportion of Ia-bearing macrophages, but not all cultures with similarly high proportions of Ia-bearing cells presented KLH to the hybridoma. Indeed, the induction of Ia on all cells in all cultures increased the proportion of KLH-presenting subcultures only about twofold. The results show that not all splenic macrophages have the ability to process KLH and present it to a T-cell hybridoma. This suggests the presence of functionally specialized subpopulations of macrophages, possibly derived from distinct progenitors, in the spleens of mice.

Animals↗