Biomedical subjects

S J Mentzer

Publications and source records attributed to S J Mentzer.

At least 73 records · Page 4Linked to original sources

PubMed1995

Expression of membrane glycoconjugates on sheep lung endothelium.

BACKGROUND: Carbohydrates play an important role in both the regulation and expression of endothelial cell surface molecules. EXPERIMENTAL DESIGN: To investigate the molecular phenotype of endothelial cells in the sheep lung, we used a panel of 39 lectins and carefully titrated lectin histochemistry to identify small vessel glycoconjugates. Expression of glycoconjugates on isolated cells was studied by flow cytometry and lectin Western blotting. RESULTS: Eight lectins stained small vessel endothelium with minimal background staining. To confirm cell surface binding, endothelial cells from the peripheral lung were isolated and tested for lectin recognition by flow cytometry. Three lectins (Datura stramonium, Griffonia simplicifolia-1, Lycopersicon esculentum) also stained isolated lung cells by flow cytometry. A lectin Western transfer technique demonstrated common binding to a high molecular weight (100 to 130 kD) band. CONCLUSIONS: The use of lectins as probes of cell surface carbohydrate expression supports the possibility of selective glycoconjugate expression on sheep endothelium.

Animals↗

PubMed1995

Immunoreactivity in lung cancer.

Lung cancer has been associated with suppression of the cellular immune system. Recent experimental evidence suggests that recognition of HLA class I molecules by cytolytic T lymphocytes is important for tumor resistance. Augmentation of this interaction may soon play a role in cancer therapy.

Adjuvants, Immunologic↗

PubMed1994

o-phthaldehyde fluorescence microassay for the determination of antibody concentration.

o-Phthaldehyde (OPA) reagent reacts with primary amines in aqueous solution at room temperature. When the reaction occurs in the presence of 2-mercaptoethanol, a bright blue fluorescence is produced. We investigated the application of the OPA reagent in the routine determination of monoclonal antibody concentration. The OPA reagent produced maximal fluorescence within 30 min and was stable for 2 h. Buffers containing primary amines gave high background fluorescence; however, the OPA reagent gave reliable results with the most commonly used antibody solutions. The OPA reagent provided a rapid and simple measure of protein concentration from 1 microgram to 1 mg and was readily adapted for use with a 96-well fluorescence reader.

Amines↗

PubMed1994

Single-lung transplantation in situs inversus.

Situs inversus totalis is a rare anatomic condition characterized by the mirror-imaged arrangement of asymmetric thoracic and abdominal organs. Although associated cardiopulmonary disease is uncommon, end-stage lung disease can develop in patients with situs inversus, necessitating transplantation. In this report, we describe a 30-year-old patient with situs inversus totalis and end-stage pulmonary hypertension who underwent successful orthotopic left lung transplantation.

Adult↗

PubMed1994

Affinity membrane identification of immunoglobulin subclass in hybridoma screening.

Monoclonal hybridomas secrete immunoglobulins with a single antigen specificity and distinct class/subclass structure. Hybridoma management has commonly incorporated tests of antigen specificity into early screening procedures, but has not typically utilized assays of immunoglobulin structure. In this article, we describe a technique of class/subclass typing using polyvinylidene difluoride affinity membranes and a colorigenic enzymatic amplification system. The typing of monoclonal antibody structure was sufficiently sensitive to permit its routine use within several weeks of hybridoma fusion. The information obtained from early and routine class/subclass determinations included a semiquantitative assessment of monoclonal antibody concentration. In addition, the detection of a single immunoglobulin class/subclass in a microtiter well supernatant supported the possibility that the colony was monotypic. The application of class/subclass typing and Poisson statistics to hybridoma fusions provided a numerical estimate of the probability of colony monotypia.

Antibodies, Monoclonal↗

PubMed1994

Mediastinal invasion by bronchogenic carcinoma: CT signs.

PURPOSE: To determine the accuracy of computed tomographic (CT) signs in assessment of direct mediastinal invasion by primary bronchogenic carcinoma. MATERIALS AND METHODS: In 90 patients with primary bronchogenic carcinoma who underwent CT with thoracic surgical staging and thoracotomy, the pathologic and CT findings in 14 mediastinal structures were compared retrospectively. The degree of contact of the primary tumor with each structure and whether the structure was distorted or contained intraluminal tumor were recorded. A total of 785 mediastinal structures (25 with tumor invasion) were analyzed. RESULTS: When greater than 90 degrees of contact was considered a positive CT finding, the sensitivity of CT was 40% (10 of 25 structures); specificity, 99% (752 of 760 structures); and positive and negative predictive values, 56% and 98%. All structures with > 180 degrees of contact had pathologic involvement, but only 11 of 17 distorted structures (65%) and five of seven structures with intraluminal tumor (71%) were involved. CONCLUSION: CT is insensitive in detection of mediastinal invasion by primary bronchogenic carcinoma. The positive predictive value may be higher, depending on the criteria used.

Carcinoma, Bronchogenic↗

PubMed1994

Membrane glycoconjugates expressed on sheep airway epithelium.

In mammalian lung, selective airway inflammatory reactions have been associated with viral infections, transplant rejection, and autoimmune diseases. Although the molecular basis for this selective reactivity is unknown, the importance of carbohydrates in immunologic processes suggests a potential role for membrane glycoconjugates in tissue-specific inflammatory reactions. In the present work we examined a panel of 39 lectins for their pattern of reactivity in the peripheral airways of the sheep lung. The size of the panel facilitated a comprehensive description of the glycoconjugate localization on the airway epithelium. Four lectins (agglutinins for Helix aspersa, Psophocarpus tetragonolobus, Trichosanthes kirilowii, and Griffonia simplifolia II) revealed selective reactivity with the small airway epithelium. On lectin Western blotting, these four lectins demonstrated a common low molecular weight banding profile that was distinct from control lectins. The histochemical staining patterns and Western blotting profiles provided evidence for the selective expression of membrane glycoconjugates in the peripheral airways of the sheep lung.

Animals↗

PubMed1993

Oxygen tension regulates neutrophil adhesion to human endothelial cells via an LFA-1-dependent mechanism.

Extravasation of leukocytes at the sites of ischemia-reperfusion is thought to exacerbate the tissue injury. It has been proposed that leukocyte accumulation is a secondary effect of the ischemic damage, mediated by inflammatory cytokines. We have recently demonstrated that physiologically low levels of oxygen tension alone can have a direct effect on the adhesive characteristics of mesenchymal cells for lymphocytes. We now report that decrease of oxygen tension in the environment induces the adhesion of neutrophils to human endothelial cells in culture. Adhesion of human neutrophils to human umbilical vein, bovine aortic, and mouse microvascular endothelial cell monolayers, which had been incubated at pO2 of 50 torr for 3 hours, increased 2.5-fold, 2-, and 1.5-fold, respectively. The effects of decreased oxygen concentration on adhesion were not mediated by a soluble factor elaborated by the hypoxic cells. Low oxygen tension upregulates a saturable, endothelial cell-associated adhesion mechanism, capable of withstanding centrifugation forces greater than 160g. Hypoxia-induced adhesion was inhibited by LFA-1-specific (CD11a/CD18 integrin) antibodies, but not by antibodies directed against the ICAM-1 ligand for the LFA-1 receptor. These studies demonstrate that decreases in oxygen tension alone increase the adhesive properties of endothelial cells for leukocytes. In addition, they provide evidence for the existence of a new ligand for the LFA-1 molecule on endothelial cells which can be affected by hypoxic environments.

Animals↗

PubMed1993

Selected benefits of thoracotomy and chemotherapy for sarcoma metastatic to the lung.

To determine the benefit of aggressive surgical therapy, we studied 77 consecutive patients presenting to our sarcoma registry with pulmonary metastases. Detailed follow-up was available on all patients; the median follow-up of the 13 long-term survivors was 72 months from the date of diagnosis of the primary tumor. Survival of these 77 patients with metastatic disease was independent of the size, location, and histology of the primary tumor. Once metastases developed, survival of patients with pulmonary metastases was not influenced by the extent of surgical resection of the primary tumor or by the use of radiation therapy. Pulmonary metastases were initially treated with thoracotomy and metastasectomy in 34 patients. The median survival after thoracotomy was 26 months. Seven patients were alive more than 4 years after their diagnosis. Pulmonary metastases were treated with chemotherapy alone in 43 patients. Although the survival was shorter (median survival 14 months) in patients treated with chemotherapy, an objective response to chemotherapy was obtained in 13 (30%) patients. Four of these patients were alive 4 years after their diagnosis. These data demonstrate that both thoracotomy and chemotherapy are associated with long-term survival of patients with sarcoma metastatic to the lung.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1993

Staged antrectomy and thoracoscopic truncal vagotomy for perforated peptic ulcer disease.

We report the case of a 40-year-old man with a perforated duodenal ulcer who underwent antrectomy at laparotomy, and in whom standard truncal vagotomy was not technically possible due to an intraabdominal abscess. Thoracoscopic truncal vagotomy performed at the level of the inferior pulmonary vein was successful in completely eliminating symptoms due to peptic ulcer disease without producing clinically significant morbidity. The minimal morbidity and short hospital stay suggest that thoracoscopic truncal vagotomy provides a reasonable alternative in patients with complicated intraabdominal abscesses due to peptic ulcer disease.

Adult↗

PubMed1993

Hypoxia induces lymphocyte adhesion to human mesenchymal cells via an LFA-1-dependent mechanism.

We and others have previously reported that mesenchymal cells, including endothelial and muscle cells, sense oxygen tension and respond in a specific way during exposure to hypoxic environment. We have examined the interactions of human muscle and endothelial cells, which have been exposed to hypoxic environments, with T and B lymphoid cell lines and peripheral blood lymphocytes (PBL), not subjected to hypoxia. The adhesion of B lymphocyte cell line (JY) and the adhesion of T lymphocyte cell line (Jurkat) to muscle cell monolayers that had been incubated at PO2 of 50 Torr for 3 h increased more than four- and twofold, respectively. Hypoxia appears to upregulate a saturable muscle cell-associated adhesion mechanism, which is capable of withstanding distraction forces greater than 45 g, and is inhibitable by LFA-1-specific monoclonal antibodies (MAbs). Hypoxia also induced a reciprocal decrease in lymphocyte-muscle cell adhesion mechanisms inhibitable by VCAM-1- or VLA-4-specific MAbs. Cultured human endothelial cells when subjected to hypoxic conditions also increased their adhesion for lymphoid cells and cell lines. This induction of adhesion could again be attenuated by anti-LFA-1, but not by anti-ICAM-1 MAb, suggesting that hypoxia activates an adhesion molecule on human mesenchymal cells that is likely to be a new ligand for LFA-1. This report is the first demonstration of a direct induction of cell adhesion mechanisms by hypoxic environments.

Antibodies, Monoclonal↗

PubMed1993

Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma.

PURPOSE: We studied a multimodality approach using extrapleural pneumonectomy, chemotherapy, and radiotherapy in patients with malignant pleural mesothelioma. PATIENTS AND METHODS: From 1980 to 1992, 52 selected patients, underwent treatment. Median age was 53 years (range, 33 to 69). Initial patient evaluation was performed by a multimodality team. Pathologic diagnosis was reviewed and confirmed before therapy. Patients with no medical contraindication and potentially resectable mesothelioma on computed tomography (CT) (magnetic resonance imaging [MRI] when it became available) received extrapleural pneumonectomy, cyclophosphamide, doxorubicin, and cisplatin (CAP) chemotherapy, and radiotherapy. RESULTS: Perioperative morbidity and mortality rates were 17% and 5.8%, respectively. The overall median survival duration is 16 months (range, 1 month to 8 years). The 32 patients with epithelial histologic variant had 1-, 2-, and 3-year survival rates of 77%, 50%, and 42%, respectively. Patients with mixed and sarcomatous cell disease had 1- and 2-year survival rates of 45% and 7.5%; no patient lived longer than 25 months (P < .01). At resection, positive regional mediastinal lymph nodes were found in 13. Positive lymph nodes were associated with poorer survival than were negative nodes (P < .01). Patients with epithelial variant and negative mediastinal lymph nodes had a survival rate of 45% at 5 years. CONCLUSION: Multimodality therapy including extrapleural pneumonectomy has acceptable morbidity and mortality for selected patients. Prolonged survival occurred in patients with epithelial histologic variant and negative mediastinal lymph nodes. These data provide a rationale for a revised staging system for malignant pleural mesothelioma; furthermore, they permit stratification of patients into groups likely to benefit from aggressive multimodality treatment.

Adult↗

PubMed1993

Preoperative assessment of patients undergoing pulmonary resection.

A careful preoperative assessment of patients with lung cancer is essential for identifying those at high risk for morbidity and mortality related to the surgical procedure. The clinician must assess the risk associated with such treatment, decide whether the risk is prohibitive, and institute therapy to reduce such risk. Testing modalities used in the preoperative evaluation include spirometry, full pulmonary function tests, measurement of arterial blood gases, radionuclide lung scanning, exercise testing, invasive measurement of pulmonary artery pressure, and a variety of studies involving lobar occlusion or lateral position testing. Studies evaluating the utility of these procedures are reviewed. Additionally, the impact of advanced age on postsurgical outcome is evaluated, as are the possibility of operating on high-risk patients and the use of preoperative interventions.

Aged↗

PubMed1993

Surgical resection in the management of small-cell carcinoma of the lung.

Surgery has had little impact on long-term survival in patients with small-cell lung cancer (SCLC). With the evolution of modern techniques, however, surgery may play an increasingly valuable role in SCLC. Surgery may potentially cure a select minority of SCLC patients. Patients with peripheral nodules and those with regional disease achieving a complete response to chemotherapy may benefit from adjuvant surgical resection for removal of residual disease. In some cases, surgery may also be preferred over adjuvant radiotherapy, since the latter necessitates lowering the total chemotherapy dose administered to SCLC patients.

Carcinoma, Small Cell↗

PubMed1993

Extrapleural pneumonectomy in the setting of a multimodality approach to malignant mesothelioma.

The use of extrapleural pneumonectomy in a multimodality treatment setting for malignant pleural mesothelioma is described, presenting first the right-sided approach and then the left-sided. This technique used in a multimodality approach with CAP chemotherapy (cyclophosphamide 600 mg/m2, doxorubicin 60 mg/m2, cisplatin 75 mg/m2) 5 cycles at 3-week intervals, and radiotherapy (55 Gy radiation to sites of previous bulky disease or residual disease) to treat 44 patients with malignant pleural mesothelioma resulted in improved operative mortality and decreased length of hospital stay.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1993

Sleeve lobectomy, segmentectomy, and thoracoscopy in the management of carcinoma of the lung.

In patients with lung cancer, the goals of limited resection procedures of the lung and major airways are to provide an adequate cancer operation while preserving functioning lung tissue. Discussed in this article are sleeve lobectomy, an alternative to pneumonectomy in patients with cancer in a lobar orifice; segmentectomy or wedge resection, an alternative to lobectomy in those with a peripheral lung cancer; and thoracoscopy, an alternative to open thoracotomy for various chest malignancies.

Bronchi↗

PubMed1993

Multimodality therapy of patients with stage IIIA, N2 non-small-cell lung cancer. Impact of preoperative chemotherapy on resectability and downstaging.

To assess the effect of neoadjuvant platinum-based chemotherapy on resectability, stage of disease at resection, and patterns of recurrence and survival in patients with IIIA, N2 non-small-cell lung cancer, we examined the first 60 patients treated with neoadjuvant chemotherapy followed by attempted resection in our institution. Of 67 patients identified, 7 patients were ineligible because of comorbidities, 3 patients refused chemotherapy, and 1 consented but died before treatment. Fifty-six received neoadjuvant chemotherapy. Complications of chemotherapy were minor, with no deaths. Fifty-four patients had thoracotomy; 75% (n = 42) had complete resection and 25% (n = 14) had unresectable lesions. One postoperative death occurred (2%). Pathologic review of specimens and nodal groups revealed that 41% (n = 23) were downstaged, 39% (n = 22) remained stage IIIA, and 19% (n = 11) progressed. Squamous histologic type was predictive of resectability, 18 of 20 patients having resectable squamous cell tumors (p < 0.05). Actuarial survivals at 1 and 2 years were 74% and 52%, respectively. In patients with resectable tumors survivals at 1 and 2 years were 85% and 67%, respectively. For those with unresectable lesions, survivals were 43% and 14%. Relapse-free survivals at 1 and 2 years for patients with resectable lesions were 70% and 42%, respectively. Relapses were local in 25% (n = 4), at a distant site only in 50% (n = 8), combined local and distant in 25% (n = 4). Distant relapse occurred in the central nervous system only in 7 of 8 patients (88%). Complete resectability was highly predictive of improved survival (p < 0.0002). Weight loss did not affect resectability but was associated with decreased survival (p < 0.003). Neoadjuvant chemotherapy appears to improve resectability and to pathologically downstage N2 non-small-cell lung cancer from stage IIIA. Multiinstitutional randomized trials are needed to further demonstrate the efficacy of this approach.

Adenocarcinoma↗

PubMed1993

Patterns of lung involvement by malignant lymphoma.

BACKGROUND: Recent evidence has suggested that the anatomic distribution of malignant lymphomas may reflect important differences in biologic behavior. To determine if the anatomic distribution of malignant lymphomas in the lung correlated with the disease course, we examined the pattern of lung involvement in patients with Hodgkin's and non-Hodgkin's lymphomas. METHODS: We reviewed the medical records of 651 patients with a diagnosis of malignant lymphoma and identified 54 patients with histologically documented lung involvement. Based on radiologic and surgical findings, these patients had lung involvement characterized as either (1) bronchovascular-lymphangitic, (2) nodular, or (3) alveolar. The pattern of lung involvement was correlated with clinical manifestations and disease course. RESULTS: Distinct clinical courses were associated with these three patterns of lung involvement. In contrast, traditional histopathologic classification did not correlated with the pattern of lung involvement was a poor prognostic factor and was associated with a median survival of 12 1/2 months. Pleural effusions eventually developed in 24 patients and were associated with a median survival of only 3 months. CONCLUSIONS: These findings suggest that the anatomic pattern of lung involvement is a measure of biologic behavior and may be a useful variable in the staging of patients with malignant lymphoma.

Adolescent↗