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Biomedical subjects

J Linder

Publications and source records attributed to J Linder.

At least 109 records · Page 6Linked to original sources
PubMed1989

Bronchial epithelial cells release chemoattractant activity for monocytes.

Lung macrophages are monocyte-derived cells that play a central and essential part in local immunity. Because the bronchial epithelial cells that line the airway can modulate their local cellular environment by releasing chemotactic factors for neutrophils, lymphocytes, and fibroblasts, we postulated that the bronchial epithelial cells might release chemotactic activity for monocytes. To test this hypothesis, bovine bronchial epithelial cells were isolated and cultured. The supernatant fluids were collected at 12, 24, 36, 48, 72, 96, and 120 h and evaluated for monocyte chemotactic activity, using a blind-well chamber technique. The supernatant fluids possessed significantly greater chemotactic activity than medium alone, with optimal migration contained in supernatant fluids harvested at 72 h (5.8 +/- 2.3 vs. 39.8 +/- 2.8 cells/high-power field, P less than 0.001). Partial characterization of the released monocyte chemotactic activity revealed that the cells released a low-molecular-weight lipid-soluble chemotactic factor after 24 h in culture, but in contrast, a high-molecular-weight protein chemokinetic factor was released after 72 h in culture. These findings suggest that bronchial epithelial cells may release chemotactic activity for, and thus may modulate the recruitment of, monocytes into bronchial passages.

Adult↗
PubMed1989

Lung fibroblasts produce chemotactic factors for bronchial epithelial cells.

The interaction between the epithelial cells and the subjacent mesenchymal cells in the airway is thought to play a major role during tissue repair and morphogenesis. To evaluate this interaction, we cultured human lung fibroblasts and bovine bronchial epithelial cells and determined that fibroblast-conditioned medium has chemotactic activity for bronchial epithelial cells. This activity was nondialyzable, heat labile, pepsin labile, acid stable, lipid inextractable, and eluted from Sephadex G-150 column chromatography in the high-molecular-weight range. DEAE-Sephacyl ion exchange and gelatin-Sepharose affinity chromatography revealed two peaks containing chemotactic activity, one of which may be fibronectin, since it binds to gelatin, reacts in a specific immunoassay, and is inhibited of chemotactic activity by anti-fibronectin antiserum, and another of which does not appear to be fibronectin, since it does not bind to gelatin nor react in the immunoassay. Thus lung fibroblasts can produce at least two chemotactic factors for bronchial epithelial cells that may play a role during lung tissue repair and morphogenesis by modulating bronchial epithelial cell migration.

Animals↗
PubMed1989

Bronchial epithelial cells produce lung fibroblast chemotactic factor: fibronectin.

The interaction between the epithelial cells and the subjacent mesenchymal cells in the airway is thought to play a major role during tissue repair after airway injury and lung morphogenesis. To evaluate this interaction, we cultured human lung fibroblasts, and bovine and human bronchial epithelial cells, and determined that bronchial epithelial cell-conditioned medium has a chemotactic activity for lung fibroblasts. This activity had the characteristics of protein: it was nondialyzable, heat-labile, pepsin-labile, acid-stable, and lipid-inextractable. Molecular sieve chromatography on Sephadex G-150 and affinity chromatography on gelatin-Sepharose revealed that there was one peak of chemotactic activity in high molecular weight range, which bound to gelatin, thus suggesting that the chemotactic factor might be fibronectin. Production and secretion of fibronectin into the culture media were demonstrated by biosynthetic incorporation of radioactive amino acid into fibronectin followed by immunoprecipitation on SDS-PAGE and autoradiography. Release into the culture medium was confirmed by ELISA. The identity of fibronectin as the chemotactic activity was confirmed by the addition of antifibronectin antibody to the conditioned medium, which inhibited chemotaxis in dose-dependent manner. Thus, bronchial epithelial cells produce fibronectin which can function as a chemotactic factor for lung fibroblasts. This production of fibronectin by bronchial epithelial cells may play an important role in regulating interaction between the bronchial epithelial cells that line the lumenal surface of the bronchial epithelial wall and the mesenchymal fibroblasts that underlie the bronchial epithelial basement membrane.

Antibodies↗
PubMed1989

Clinical significance of immunophenotype in diffuse aggressive non-Hodgkin's lymphoma.

We performed a prospective study of the clinical significance of immunophenotype in 110 patients with aggressive non-Hodgkin's lymphoma (NHL) treated by oncologists in the Nebraska Lymphoma Study Group between October 1982 and May 1986. All patients were immunophenotyped from biopsies performed before therapy was administered. The patients were treated with a uniform protocol of radiotherapy for minimal nonbulky, stage I or II disease (seven patients) or a single, six-drug chemotherapy regimen cyclophosphamide, doxorubicin, procarbazine, bleomycin, vincristine, and prednisone (CAP-BOP) in patients with more extensive disease (103 patients). Ninety-one patients (83%) had B-cell lymphoma and 19 patients (17%) had T-cell lymphoma. The histologic diagnosis of diffuse mixed-cell lymphoma was significantly associated with T-cell immunophenotype (45% v 5%; P less than .001), and the diagnosis of diffuse large-cell lymphoma was significantly associated with B-cell immunophenotype (40% v 5%; P = .006). However, no significant difference in frequency of prognostic variables such as age, stage, systemic symptoms, tumor bulk, serum lactic dehydrogenase, or performance status was found between the B-cell and T-cell groups. Patients with B-cell NHL had a slightly higher complete remission rate (74% v 53%; P = NS), similar durability of complete remission (75% v 70% at 3 years; P = NS), and a slightly but not significantly better overall survival (50% v 41% at 3 years; P = NS). The slight advantage in response rate and survival for B-cell patients was related to a very poor outcome for patients with stage IV T-cell NHL. For patients with stage I to III disease, neither the complete remission rate (B-cell, 82% v T-cell, 91%; P = NS) nor overall survival (3-year survival for B cell, 58% v T cell, 73%; P = NS) were significantly different. However, with stage IV disease B-cell patients fared far better than those with T-cell NHL for both complete remission rate (67% v 0%; P = .002) and overall survival (3-year survival, 44% v 0%; P = .002). Immunophenotyping intermediate- and high-grade NHL allowed identification of a subgroup of patients who had a very poor prognosis with this treatment approach and for whom alternate therapy might be considered.

Antigens, CD↗
PubMed1989

Phenotypic analysis of infiltrating cells in human myocarditis. An immunohistochemical study in paraffin-embedded tissue.

To define the cellular subpopulations that infiltrate the heart in human myocarditis, formaldehyde-fixed, paraffin-embedded sections from 18 hearts with histologically proved myocarditis were examined immunohistochemically. Disease was classified on routine stains as follows: mixed mononuclear cell (7 cases), granulomatous (3), giant cell (1), rheumatic (2), and fungal (5) myocarditis, respectively. On immunohistochemical examination, T-lymphocyte and macrophage predominance was found in nearly every case, except in fungal myocarditis, in which polymorphonuclear leukocytes and macrophages prevailed. In contrast, B lymphocytes and natural killer cells were conspicuously absent, regardless of histologic classification. Giant cells in giant cell myocarditis and in the Aschoff lesions of rheumatic carditis expressed macrophage, but not myocyte, antigens, suggesting derivation along macrophage lineage. Immunohistochemical data obtainable in paraffin-embedded tissues supplement the study of myocarditis, providing information potentially relevant to immunopathogenesis, natural history, and therapy.

Cell Line↗
PubMed1989

Immunohistochemistry of Pneumocystis carinii.

The recent explosion in the acquired immune deficiency syndrome epidemic brought about an increased need for specific markers that recognize Pneumocystis carinii. Newly developed antibodies mark cyst and/or trophozoites, but have not been thoroughly characterized. While the sensitivity of the immunocytochemical method appears greater than that offered by the Giemsa strain, it is only slightly better than that of GMS stain. That slight edge in sensitivity warrants the use of immunostaining in specimens such as sputum, where identification of Pneumocystis carinii as the sole pathogen is more difficult than in bronchoalveolar lavage. In the latter specimen, we still recommend rapidly performed GMS with the microwave technique because of its utility in recognizing fungi. With refinements in the antibodies available, immunostaining may offer further advantages in patient management.

Animals↗
PubMed1989

Breast carcinoma in bronchoalveolar lavage. A cytologic and immunocytochemical study.

To evaluate the effectiveness of bronchoalveolar lavage in detecting pulmonary metastases of breast cancer, we examined lavage fluid from 20 patients with routine cytologic preparations and immunoperoxidase stains with monoclonal antibody B72.3. Bronchoscopy was performed for infection surveillance prior to autologous bone marrow transplantation (nine patients), or to assess abnormal chest roentgenogram (11 patients). Metastatic adenocarcinoma was identified on Papanicolaou-stained-membrane filters in seven patients (35%), corroborated by transbronchial biopsy in four patients. No patients with chest roentgenogram suggestive of metastatic cancer or transbronchial biopsy positive for metastatic cancer had a negative lavage. Monoclonal antibody B72.3 uniformly marked malignant cell aggregates and many single cells that were inapparent in routinely stained material. Because bronchoalveolar lavage may detect metastatic adenocarcinoma with sensitivity comparable to transbronchial biopsy but with less morbidity, it is useful in the evaluation of pulmonary infiltrates in patients with primary breast carcinoma. Staining with monoclonal antibody B72.3 can be readily performed on lavage specimens and may serve as an adjunct in diagnosing malignancy.

Adenocarcinoma↗
PubMed1988

Correlation of secondary cytogenetic abnormalities with histologic appearance in non-Hodgkin's lymphomas bearing t(14;18)(q32;q21).

Successful cytogenetic studies were performed on 69 biopsies from 64 patients with non-Hodgkin's lymphoma bearing a t(14;18)(q32;q21) translocation. This translocation appears to be a primary abnormality associated with the development of certain B-cell non-Hodgkin's lymphomas. We correlated the occurrence of secondary abnormalities, in addition to the t(14;18)(q32;q21), with histologic subtype to test the hypothesis that secondary abnormalities correlate with more aggressive histologic appearance. A large number of secondary abnormalities were identified, the most frequent being additional copies of chromosomes 7 (30%), 12 (22%), 18 (22%), 20 (16%), or 21 (14%), deletion of a portion of the long arm of chromosome 6 (17%), and either an additional chromosome 17 or an isochromosome for the long arm of chromosome 17 (13%). An extra chromosome 7 was highly associated with a diffuse histologic pattern; it was present in 52% of patients with a diffuse pattern and in only 15% of those with a follicular pattern (P = .002). A weaker association with a diffuse growth pattern was found for the addition of chromosome 17 or an i(17q); it was found in 24% of patients with a diffuse pattern and only 5% of those with a follicular pattern (P = .05). No other significant correlations between secondary chromosome abnormalities and histologic subtype were identified. Although the explanation for this association is not clear, it appears that patients with B-cell non-Hodgkin's lymphomas bearing the t(14;18)(q32;q21) translocation which also have an additional chromosome 7 are likely to exhibit a diffuse growth pattern.

B-Lymphocytes↗
PubMed1988

Flow cytometric DNA analysis of malignant fibrous histiocytoma and related fibrohistiocytic tumors.

Fibrohistiocytic neoplasms with similar histologic characteristics may have vastly different biologic behaviors. We studied 23 fibrohistiocytic tumors to determine if cellular DNA content was correlated with clinical outcome. Archival paraffin blocks of 9 malignant fibrous histiocytomas (MFH), 3 dermatofibrosarcoma protuberans, 9 dermatofibromas, 1 juvenile xanthogranuloma, and 1 nodular fasciitis were processed, stained with propidium iodide, and analyzed by flow cytometry. Five of 9 (56%) MFH and 1 of 3 (33%) dermatofibrosarcoma protuberans were aneuploid. All 11 benign fibrohistiocytic tumors were diploid. Local recurrence occurred in 3 of 5 (60%) cases of aneuploid MFH, but in none with a diploid MFH tumor. No cases of dermatofibrosarcoma protuberans or benign tumors recurred. Aneuploidy was associated with decreased survival, as 2 of 5 patients with aneuploid MFH died within 1 year of diagnosis whereas all 4 patients with diploid MFH tumors are alive after an average follow-up of 4 years (range, 1 to 11). The diploid and aneuploid groups did not differ in clinical stage at the time of diagnosis. Our results indicate that retrospective DNA analysis can detect aneuploidy in both MFH as well as other fibrohistiocytic tumors, and that aneuploidy in MFH may place the patient at increased risk for local recurrence and mortality.

DNA↗
PubMed1988

Rapid identification of cytomegalovirus in liver allograft biopsies by in situ hybridization.

Identifying the etiology of hepatic dysfunction in liver transplant patients is critical to their clinical management and in maintaining graft survival. While cytomegalovirus (CMV) is a well-known cause of posttransplant hepatitis, the morphologic diagnosis of CMV hepatitis in liver biopsies can be difficult. Because conventional tissue culture for CMV requires days to weeks, the final results often arrive too late to be clinically useful. In this study, 44 liver allograft biopsies from 21 patients with hepatic dysfunction were evaluated for CMV by routine light microscopy, conventional tissue culture, and in situ DNA hybridization (IH) using commercially available biotinylated CMV-specific DNA probes. Whereas 38.6% of the biopsy specimens were positive by IH, 15.9% were culture-positive biopsies and 13.6% were positive by routine light microscopy. Assuming tissue culture to be the standard, IH demonstrated a sensitivity of 100% and a specificity of 73%. In comparison, routine light microscopy showed a sensitivity of 71.4% and specificity of 97.3%. In addition, three biopsy specimens positive only by IH were from three patients who had other liver biopsies positive for CMV by either light microscopy or viral culture. In situ DNA hybridization allows rapid detection (5-6 h) of CMV in paraffin-embedded liver allograft biopsies; it also has a sensitivity that surpasses routine histologic examination and perhaps even tissue culture.

Adolescent↗
PubMed1988

Characteristic changes in psychiatric symptoms, cortisol and melatonin but not prolactin in primary hyperparathyroidism.

Psychiatric symptoms in primary hyperparathyroidism (PHPT) are usually characterized as depressive. In this study 13 patients with PHPT and six control patients with atoxic nodular goiter underwent psychiatric ratings with the comprehensive psychopathological rating scale (CPRS) the day before surgery. The 21 items in this scale were grouped into clusters. The ratings were repeated after successful removal of a parathyroid adenoma. Diurnal serum concentrations of cortisol, melatonin and prolactin were studied pre- and postoperatively in eight of the patients. Patients with PHPT had significantly higher CPRS total scores, 8.5 +/- 1.3, compared with goiter controls, 1.9 +/- 0.8, and showed a significant improvement of psychiatric symptoms after excision of the parathyroid adenoma, to 3.3 +/- 0.9. The preoperative diurnal and peak levels of cortisol and melatonin were higher (P less than 0.05) than after surgery. Serum melatonin fell to levels lower than those in healthy controls. Correlations were found between some clusters or items and cortisol or melatonin. Serum prolactin levels were normal and unaltered by parathyroid surgery. It is concluded that patients with PHPT show well defined psychiatric symptoms many of which are correlated to alterations in serum cortisol and melatonin accompanying PHPT. The improvement of symptoms seen after successful surgery further suggests that PHPT is associated with a specific psychiatric disorder similar to but distinguishable from major depressive disorder.

Adenoma↗
PubMed1988

Mechanisms of neutrophil recruitment to the lung by grain dust exposure.

Inhalation of grain dusts can cause symptoms of both acute and chronic bronchitis, which has been associated with a neutrophilic inflammatory response in the lung. Since this influx of neutrophils may potentially result in bronchial injury, mechanisms of neutrophil recruitment to grain dust were examined. Sterile, aqueous grain dust extracts were prepared from settled dusts of grain sorghum, corn, oats, and soybeans. The extracts were evaluated for their ability to directly attract human neutrophils using a blindwell neutrophil chemotaxis assay. Each extract was found to possess significant chemotactic activity compared to control (p less than 0.01). To evaluate if the dusts could attract neutrophils indirectly by activating humoral inflammatory mechanisms, the grain dust extracts were evaluated for their ability to activate the complement system. When incubated with normal human serum, each of the grain dusts caused cleavage of the complement proteins C3 and properdin factor B (PFB). Importantly, the grain dust extracts lead to the generation of C5a, a potent neutrophil chemoattractant generated by complement activation. Since activation of the alveolar macrophage to release chemotactic activity represents an additional indirect mechanism of neutrophil recruitment, an extract from grain sorghum dust was evaluated for its ability to stimulate guinea pig and human alveolar macrophages to release neutrophil chemotactic activity. The results demonstrate that supernatants obtained from alveolar macrophages cultured in the presence of grain sorghum dust extract possessed increased chemotactic activity compared to controls (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Biomechanical Phenomena↗
PubMed1988

Immunohistochemistry with monoclonal antibody B72.3 as an adjunct in the cytologic diagnosis of pancreatic carcinoma.

Due to the morbidity of open tissue biopsy, the cytologic diagnosis of pancreatic carcinoma by fine needle aspiration or examination of biliary tree fluid is highly desirable. Immunohistochemistry with monoclonal antibody B72.3 has been advocated as an adjunct in the identification of tumor cells in body fluids. To assess its usefulness as an adjunct in the diagnosis of pancreatic carcinoma, we examined cytologic specimens of the pancreas from 35 patients [24 pancreatic carcinoma, 6 metastases (4 adenocarcinoma and 1 each of Hodgkin's disease and melanoma), 5 with benign conditions] with an immunohistochemical procedure using B72.3 directly over the Papanicolaou-stained slides. Of the pancreatic carcinomas, 21 of 24 (87%) were cytologically positive and 21 of 24 (87%) marked with B72.3. With both techniques, 23 of 24 cases (96%) could be identified. Three of four metastatic adenocarcinomas were positive by both cytology and B72.3. No staining occurred in the metastatic melanoma, Hodgkin's disease, or 3 of 5 benign conditions. In two benign duodenal aspirates, an unusual reticular B72.3 staining occurred in the mucin of acinar and goblet cells which could be misinterpreted as positive staining. In our experience, B72.3 enhances the sensitivity of the cytologic diagnosis of pancreatic cancer. Unrecognized single tumor cells, cytologically uninterpretable cells, and tumor cell clusters that could be misinterpreted as reactive epithelium mark with B72.3. Care should be taken to avoid misinterpretation of nonspecific mucin staining with this antibody.

Adenocarcinoma↗
PubMed1988

Soluble interleukin 2 receptors in patients with malignant lymphoma.

We performed a retrospective analysis of serum interleukin 2 receptor (IL-2R) levels in a group of 35 patients with malignant lymphoma (ML; 13 T cell and 22 B cell) using a new enzyme immunoassay. Our objectives were to determine if elevated levels of soluble IL-2R occur in patients with active ML, whether serum IL-2R levels are prognostic, and whether prospective studies are warranted. Our preliminary data indicate that serum IL-2R levels correlate with disease activity and size of tumor, but not with grade or stage of the tumor. Five-year actuarial survival was 20% for patients with IL-2R levels greater than 1000 U/mL at any time during their course and 86% for patients who did not exceed that threshold. Furthermore, patients with IL-2R levels lower than 1000 U/mL were more likely to achieve a complete remission. Serum lactate dehydrogenase and uric acid levels did not show significant correlation with disease activity or prognosis. We conclude that serum IL-2R levels may have clinical and prognostic significance in patients with ML and that prospective studies are indicated.

Antibodies, Viral↗
PubMed1988

The presence of stage II melanosomes (premelanosomes) in neoplasms other than melanomas.

Aside from melanomas, other nonmelanocytic pigmented tumors synthesize melanin or contain benign passenger melanocytes. While Stage IV melanosomes (mature melanosomes) occur in neoplasms which synthesize melanin as well as in those with benign companion melanocytes, Stage II melanosomes (premelanosomes), which are found in melanocytes and cells of pigmented nonmelanocytic tumors of neural crest origin, are considered the morphologic hallmark of in vivo melanin synthesis. To test this widely held concept, we studied the ultrastructure of representative malignant melanomas and other pigmented tumors (pigmented variants of the nevocellular nevus, squamous cell carcinoma, schwannoma, basal cell carcinoma, and seborrheic keratosis). Discrete intracytoplasmic Stage II melanosomes were noted in neoplastic cells of tumors of neural crest origin (melanoma, schwannoma, and nevocellular nevus), which are widely believed to synthesize melanin. In addition, they were also detected in neoplastic epithelial cells of a squamous cell carcinoma, basal cell carcinoma, and seborrheic keratosis. In these epithelial tumors, a spectrum of melanosomes from Stage II through Stage IV were presumably acquired from nonneoplastic companion melanocytes, which were an integral part of the tumor. Because squamous epithelium has not been shown to synthesize melanin, this study suggests that the finding of intracytoplasmic Stage II melanosomes does not necessarily imply melanin synthesis. When accompanied by melanocytes, epithelial and perhaps other tumors may contain ingested Stage II melanosomes.

Basal Cell Carcinoma↗
PubMed1988

Monoclonal antibodies marking B-cell non-Hodgkin's lymphoma in paraffin-embedded tissue.

Traditional methods for the immunophenotypic analysis of the non-Hodgkin's lymphomas require fresh or snap-frozen tissue for flow cytometric or immunohistochemical studies. The monoclonal antibodies LN1, LN2, and L26 have been recently developed to recognize B-cell-specific antigens that survive routine tissue processing and paraffin embedding. In this study, the ability of these three antibodies to mark the neoplastic cells in 160 cases of paraffin-embedded non-Hodgkin's lymphoma relative to frozen section immunophenotype (42 T-cell, 118 B-cell), manner of fixation (B5 versus 10% buffered formalin), and histological subtype was examined. With B5-fixed tissue, the percentages of B-cell lymphoma marking with the antibodies were as follows: L26, 96.6%; LN1, 88.2%; LN2, 93.7%. With formalin-fixed tissue, the percentages of B-cell lymphoma reacting with the antibodies were: L26, 89.1%; LN1, 26.2%; LN2, 57.8%. Each of the antibodies marked a small percentage of paraffin-embedded T-cell lymphomas: L26, 4.7%; LN1, 4.7%; LN2, 7.1%. LN2, and to a lesser extent LN1, stained Reed-Sternberg cells, a feature not seen with L26. Nor did L26 mark nonlymphoid neoplasms, a feature previously reported with LN1 and LN2. Since a high percentage of B-cell lymphomas react with these antibodies and they are relatively specific for B-cells, they should prove highly useful for the evaluation of both diagnostic and experimental pathology specimens. L26 offers the distinct advantage of working well in both B5 and formalin-fixed tissues and seemingly not marking epithelial neoplasms.

Antibodies, Monoclonal↗