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J Linder

Publications and source records attributed to J Linder.

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

Lung fibroblasts produce growth stimulatory activity for bronchial epithelial cells.

Interaction between lung fibroblasts and airway epithelial cells may play an important role in lung morphogenesis and airway repair after injury. Even though many reports have suggested that mesenchymal fibroblasts have a growth stimulatory effect on surrounding epithelial cells, very few have attempted to confirm and characterize the growth stimulatory activity in isolated cell systems. We cultured human fetal lung (HFL-1) fibroblasts, harvested supernatant-conditioned media under serum-free conditions, and examined their growth stimulatory effect on bovine bronchial epithelial cells by a variety of techniques, including direct enumeration, thymidine uptake, and metaphase arrest. We also partially characterized the growth stimulatory activity and examined the effect of an inhibitor of DNA synthesis on its release. The results demonstrate that HLF-1 fibroblasts release growth stimulatory activity for bovine bronchial epithelial cells. This activity is nondialyzable, protease-sensitive, acid-stable, and lipid-inextractable and thus appears to have the property of protein; it may be produced by de novo synthesis. Molecular sieve chromatography on Sephadex G-75 indicates an approximate molecular mass of 6,000 D. This growth stimulatory activity is likely to play roles in lung morphogenesis and airway repair after injury.

Animals↗
PubMed1990

Pulmonary macrophages can stimulate cell growth of bovine bronchial epithelial cells.

Macrophages are thought to participate in tissue repair following injury by releasing growth factors into the local environment. To evaluate whether pulmonary macrophages can mediate airway epithelial repair, we attempted to determine if pulmonary macrophages can stimulate growth of bovine bronchial epithelial cells in vitro. Bronchial epithelial cells isolated by protease digestion of the bovine bronchi were plated into tissue culture dishes with and without macrophage-conditioned medium. Bronchial epithelial cells cultured with macrophage-conditioned medium showed a significantly greater cell growth than those without macrophage-conditioned medium when assessed by direct enumeration of the cell numbers and by clonal growth assay. Stimulation of proliferation was confirmed by autoradiography using [3H]thymidine uptake into cell nuclei. Co-culture of pulmonary macrophages with bronchial epithelial cells also led to an increase in cell number. Immunohistochemical staining of the proliferating cells showed that these cells were positively stained by anti-keratin antibodies confirming that they were bronchial epithelial cells. Partial characterization of the activity in macrophage-conditioned medium showed that it was nondialyzable, pepsin- and acid-labile, and lipid-inextractable. Sephadex G-75 column fractionation indicated this activity existed in a high molecular fraction, thus suggesting a peptide. DEAE ion exchange chromatography revealed 3 peaks of stimulating activity. One peak resulted in a decrease in cell number, suggesting a possible inhibitory activity. The DEAE results thus suggest that macrophages may release several factors that can affect bronchial epithelial cell proliferation. In conclusion, pulmonary macrophages stimulate cell proliferation of bronchial epithelial cells in vitro. The stimulatory activity that may be heterogeneous appears to have the properties of a peptide.

Animals↗
PubMed1990

Bronchial epithelial cells respond to insulin and insulin-like growth factor-I as a chemoattractant.

Migration of epithelial cells to cover areas of injury is thought to be important in the repair process following airway insult. Insulin is reported to be a growth factor for bronchial epithelial cells, and growth factors have been known to be chemotactic for many types of cells. Thus, we hypothesized that insulin may be a chemoattractant for bronchial epithelial cells. To evaluate this, we prepared bronchial epithelial cells and measured their chemotactic activity toward insulin. Bronchial epithelial cells were isolated by overnight digestion with bacterial protease, filtered through 100-microns nitex mesh, and then cultured at 1 x 10(6) cells/ml in tissue culture dishes in medium 199 supplemented with transferrin, insulin, epidermal growth factor, hydrocortisone, antibiotics, and 10% FCS for 3 d. The cultured cells were rinsed twice to remove supplements, trypsinized and resuspended at 1 x 10(6) cells/ml in medium 199 without supplements, and used as the cell source for chemotaxis. Chemotactic activity of bronchial epithelial cells was measured by the blindwell chamber technique using 8-microns Nuclepore filter membranes coated with 0.1% gelatin. The cells were added to the top wells in a 48-multiwell chamber with insulin in the bottom wells and incubated for 6 h at 37 degrees C, 5% CO2. Bronchial epithelial cells migrated in response to insulin in a dose-dependent manner up to an optimal dose of insulin, 100 micrograms/ml, and decreased at higher concentrations. The number of migrated cells per 10 high power fields was 33.7 +/- 1.9 at the optimum and 3.7 +/- 0.7 without insulin (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Separation of bovine bronchial epithelial cell subpopulations by density centrifugation: a method to isolate ciliated and nonciliated cell fractions.

Bronchial epithelial cells isolated by protease digestion can be cultured in vitro for the study of proliferation and differentiation. However, these cells represent a heterogenous population, the components of which likely interact with one another. We attempted to utilize density gradient centrifugation as a method to prepare subpopulations of these bronchial epithelial cells. The suspension of the cells obtained by protease digestion of the bovine bronchi was mixed with an equal volume of colloidal silica reagent, Sepracell-MN, and centrifuged to form a continuous density gradient. Two distinct cell layers were identified in addition to a cell pellet at the bottom. Cells from fraction A (top layer) were more than 95% ciliated cells by morphologic examination. These ciliated cells were recovered intact as assessed by trypan blue dye exclusion and by watching beating of their cilia. The cells from fraction C (bottom layer) were 89.9 +/- 3.88% nonciliated, small round cells with a densely staining nucleus and scant cytoplasm. Comparison of cell morphology of these cells with basal cells in vivo and electron microscopic examinations suggested that these cells were basal cells. These basal cells showed an exponential cell proliferation until confluence in Ham's F12 with supplements, LHC9, and a 1:1 mixture of Medium-199 and modified Eagle's medium with 2% fetal calf serum. In contrast, the cells from fraction A grew minimally in all conditions tested. This difference was also shown in the study of DNA synthesis by [3H]thymidine uptake. Enzyme-linked immunosorbent assay for release of bovine fibronectin into cultured media indicated that fraction C cells secreted much more fibronectin (532 +/- 5.28 ng/10(6) cells/h) than fraction A cells (73.4 +/- 1.00). We also used Percoll as a density-gradient reagent and showed potential usefulness in the preparation of cell fractions of bronchial epithelial cells. In conclusion, it was possible to separate ciliated and nonciliated, presumably basal, cells of bovine bronchial epithelial cells. These differed in growth and fibronectin secretion. Studies of airway cell biology may be aided by the availability of more homogenous cell populations.

Animals↗
PubMed1990

Detection of cytomegalovirus in bronchoalveolar lavage specimens. Spin amplification and staining with a monoclonal antibody to the early nuclear antigen for diagnosis of cytomegalovirus pneumonia.

To diagnose cytomegalovirus pneumonia in a hetergeneous population of patients, three methods for detection of CMV in bronchoalveolar lavage specimens were compared as follow: (1) spin amplification followed by staining with a monoclonal antibody to the early nuclear antigen (EA-assay); (2) conventional tissue cell culture; and (3) cytology. Cell differentials were performed on most specimens. Cytomegalovirus was detected by one or more method in 55 BAL specimens from 39 patients. Cytomegalovirus (CMV) pneumonia was diagnosed by lung tissue (primarily autopsy) histologic findings and conventional culture results or the presence of CMV in extrapulmonary tissue, fulfillment of specific clinical and radiographic criteria plus failure to recover a pathogen other than CMV from a respiratory specimen. Probable CMV pneumonia was diagnosed if only the latter two criteria were met. The EA-assay was positive in all patients with proven or probable CMV pneumonia and in 92 percent of those without documented pneumonia. Cytologic findings were positive only in patients with CMV pneumonia but were negative in one-third of those patients. As a diagnostic test for CMV pneumonia, the EA-assay, conventional culture, and cytology had positive predictive values of 45, 57, and 100 percent, respectively. Lymphocyte percentages in BAL specimens from patients with CMV pneumonia were significantly decreased compared with those of patients without CMV pneumonia (p less than 0.005). Although the EA-assay should not be used alone as a diagnostic test for CMV pneumonia in our patient population, the combination of alveolar lymphopenia and a positive BAL CMV EA-assay was highly suggestive of disease.

Adolescent↗
PubMed1990

LN-3: a diagnostic adjunct in cutaneous graft-versus-host disease.

Expression of HLA Class II antigen on keratinocytes has been advocated as a diagnostic marker of acute graft-versus-host disease (GVHD). LN-3 is a murine monoclonal antibody marking an HLA Class II antigen that survives formalin fixation and paraffin embedding. We analyzed the LN-3 staining pattern on 56 skin biopsies from patients treated with bone marrow or peripheral stem cell transplantation, non-transplant patients receiving conventional chemotherapy and/or radiation therapy and controls. Keratinocyte staining, endothelial staining, and the number of epidermal and dermal Langerhans cells were evaluated and analyzed with respect to the histologic and clinical diagnosis in a blind and retrospective fashion. The most predictive parameter for GVHD was marking of endothelial cells by LN-3 which was present in 12 of 16 (75%) biopsies from patients with GVHD. Endothelial staining was found in a total of 19 biopsies of which 12 (63%) had GVHD. These data suggest that LN-3 immunohistochemistry may help identify cutaneous GVHD and discriminate it from conditions that are histologically similar.

Antibodies, Monoclonal↗
PubMed1990

Immunohistochemistry in surgical pathology. The case of the undifferentiated malignant neoplasm.

An ideal immunohistochemical screening panel would be one in which each antibody is 100% sensitive and specific for the target cell type (e.g., markers for epithelial neoplasms, lymphomas, sarcomas, etc.). Anyone who has practiced immunochemistry is well aware that this situation does not exist. High sensitivity is hindered by the loss of key antigens through formalin fixation and routine tissue processing. Although sensitivity can be improved by dealing with fresh-frozen, lyophilized, or plastic-embedded specimens, these procedures are often perceived as inconvenient by pathologists. Specificity is a more insidious problem. With the advent of monoclonal antibody technology, many individuals equated the monospecificity (e.g., marking one antigen a determinant) with tissue specificity. This, of course, is not the case as determinants recognized by one monoclonal antibody may be expressed on cells of different lineage. High sensitivity and high specificity are important for different reasons. By definition, an undifferentiated neoplasm lacks morphologic features to unequivocally substantiate sarcoma, lymphoma, carcinoma, or melanoma. Thus, antibodies with low sensitivity that fail to mark a significant percent of cases will provide inconclusive or erroneous information. The failure of an antibody to stain a particular tissue could be a true-negative (valuable information) or a false-negative (misleading information) result. Obviously, when antibodies have a sufficiently low sensitivity, their use is a liability rather than an advantage. Specificity is obviously important. When an undifferentiated neoplasm is found to be "positive" for a particular marker, there is a tendency to immediately categorize the neoplasm. In this setting, when histologic features of cellular differentiation are totally lacking, an extreme degree of trust is being placed on the immunohistochemical technique. From our earlier discussion it is apparent that perfect sensitivity and specificity do not exist among most immunohistochemical reagents. Accordingly, the safest approach is to use a panel of antibodies that will disclose anomalous immunohistochemical reactions (e.g., a neoplasm positive for both keratin and LCA). Specimens from such cases should be carefully evaluated with additional monoclonal antibodies and scrutinized by light microscopy. Furthermore, while immunohistochemistry provides for rapid and cost-effective diagnosis, electron microscopy may still contribute valuable information. Despite our best intentions and desires, it is also clear that a small percentage of "undifferentiated" neoplasms will remain undifferentiated. Quality control and quality assurance are two final, but important, issues to address. An extraordinary large number of variables in tissue selection, fixation, and processing can skew results.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, Neoplasm↗
PubMed1990

Immunohistochemistry of Pneumocystis carinii infection.

Pneumocystis carinii is the pre-eminent pulmonary pathogen and leading cause of death in patients with acquired immunodeficiency syndrome (AIDS). The diagnosis of this organism depends upon the morphologic demonstration of the cyst wall, trophozoite, or sporozoite in specimens from the lower respiratory tract. A variety of histochemical stains have been used to identify P. carinii, each with considerable limitations in specificity. Extrapulmonary spread and unusually destructive pulmonary patterns associated with P. carinii, although once considered rare, are seen occasionally in patients with AIDS. Traditional stains have proven to be less reliable in extrapulmonary sites. In 13 patients with AIDS, we stained formalin-fixed paraffin-embedded autopsy lung and other visceral organ sections using monoclonal antibody 3F6 (Dako, Santa Barbara, CA) to P. carinii. The antibody stained P. carinii in the lungs of seven patients with P. carinii pneumonia by Gomori methenamine silver stain (GMS). Numerous aggregates of P. carinii cysts were marked within alveoli, as is usually seen with other stains. No antibody staining was present in autopsy lung sections from non-AIDS patients with viral, fungal, or bacterial pneumonia. Clinically occult extrapulmonary P. carinii infection was seen in 4/7 (57%) patients with P. carinii pneumonia at autopsy. Monoclonal antibody to P. carinii stained organisms in all four (100%) patients with disseminated disease, as compared with 1/4 (25%) staining with GMS. Antibody staining of P. carinii was demonstrated in sections of thyroid, adrenal, and carinal lymph node (one patient), esophagus (one patient), kidney (one patient), and heart, thyroid, kidney, adrenal, liver, stomach, pancreas, spleen, and bone marrow (one patient).(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1990

Neural patterns in inflammatory bowel disease: an immunohistochemical survey.

The differential diagnosis of inflammatory bowel disease remains a significant diagnostic problem for surgical pathologists. Neural abnormalities, such as hypertrophy of nerve plexi, hyperplasia of ganglion cells, and ultrastructural axonal degeneration have been described in patients with regional enteritis. We performed an immunohistochemical survey of forty cases of regional enteritis, ulcerative colitis, nonspecific colitis, and normal colon. A panel of antibodies, directed against neuron-specific enolase, S-100 protein, synaptophysin, neurofilament protein, and nerve growth factor receptor, was utilized to evaluate the distribution of nerve fibers in paraffin-embedded tissue. Anti-synaptophysin and anti-nerve growth factor receptor highlighted small, arborizing nerve fibers in the mucosa, not apparent in the routinely stained sections. Intense staining of these fibers was observed in regional enteritis with antinerve growth factor receptor. This antibody may aid the discrimination of inflammatory bowel disease from other causes of colonic inflammation and facilitate the identification of regional enteritis in endoscopic biopsies.

Colitis, Ulcerative↗
PubMed1990

Current concepts of immunodeficiency disorders.

The technical developments in immunology and molecular biology during the 1970s, the growing use of organ transplantation during this period, and the abrupt emergence of AIDS in 1981 made the 1980s a fruitful period for investigating basic mechanisms of immunodeficiency. Now armed with powerful molecular biologic techniques, such as the polymerase chain reaction, we can identify specific genes and viruses that result in immunodeficiency. Complications associated with immunodeficiency, such as malignant lymphoma and opportunistic infections, have provided pathologists with opportunities for investigating the pathogenesis of this and other related diseases. An impetus for developing new diagnostic immunologic and molecular biological methods will be sustained during the 1990s. Pathologists working in the 21st century will be participants in the use of gene therapy for primary immunodeficiency diseases and for conquering AIDS. Perhaps with the declining threat of thermonuclear annihilation, we will tackle the largest cause of acquired immune deficiency, protein-calorie malnutrition.

Adult↗
PubMed1990

Overview of digital imaging in pathology. The fifth wave.

During the last decade, pathologists have witnessed dramatic advances in computer hardware and software technology. The major impact of these technologies has been in the management of text information. Significant benefits, however, lie in the manipulation and use of digital images of pathology specimens. Digital images may be analyzed to extract feature information, processed to enhance the visual image, archived to aid diagnostic efforts and education, or transmitted to facilitate communication between pathologists. These components can be integrated with information management systems to form the basis for a work-station for diagnostic pathology. Such technology will likely improve the productivity and diagnostic ability of pathologists in the coming years.

Image Processing, Computer-Assisted↗
PubMed1990

[Effect of intravenous administration of SO4Mg in the acute phase of myocardial infarct].

Fifty four patients (p) with acute myocardial infarction (40M; 14F) were entered into a prospective study where they received either intravenous magnesium sulphate (group A-27 p) or placebo (group B-27 p). The incidence of arrhythmias necessitating treatment was greater in group B (37%) than in group A (15%). Mortality was 18.5% in group B and 3.7% in group A. These results suggest that magnesium sulphate administration reduces the incidence of arrhythmias and death after acute myocardial infarction.

Aged↗
PubMed1989

Peripheral T-cell lymphoma.

Peripheral T-cell lymphoma is the most common type of T-cell lymphoma seen in adults in the United States. Clinical data were reviewed from 134 cases of peripheral T-cell lymphoma diagnosed in three centers. The median age of the patients was 57 years (range, 4-97 years), 59% were male, and 36 patients (27%) had a history of a preceding disorder of the immune system. The tumors were grouped histologically into large cell (43%), mixed large and small cell (40%), and small cell (17%). The stage at diagnosis was I (7%), II (21%), III (22%), and IV (50%). B symptoms were present in 57%. The most frequent sites of extranodal involvement were bone marrow (35%), skin (13%), and lung (11%). Eighty patients were treated with a multiagent chemotherapy regimen with proven curative potential in aggressive non-Hodgkin's lymphomas and the remainder of the patients received less intensive chemotherapy (36 patients), radiotherapy (nine patients), or no treatment (nine patients). Fifty percent of the intensively treated patients achieved complete remission and the actuarial 4-year survival was 45%. However, the 4-year, disease-free survival in patients with Stage IV disease was only 10%. Although peripheral T-cell lymphomas appeared similar in many ways to their B-cell counterparts, disease-free survival by stage was low and patients with Stage IV disease had an especially poor outlook.

Adolescent↗
PubMed1989

Diffuse alveolar hemorrhage in autologous bone marrow transplant recipients.

PURPOSE: The purpose of our work was to evaluate pulmonary complications in autologous bone marrow transplant recipients. PATIENTS AND METHODS: A total of 141 consecutive autologous bone marrow transplant recipients were evaluated. In 29 patients, a clinical syndrome characterized by progressive dyspnea, hypoxia, cough, diffuse consolidation on chest roentgenography, and characteristic bronchoalveolar lavage findings developed over one to seven days. RESULTS: In 29 patients, bronchoalveolar lavage performed by sequential instillation and aspiration of 20-ml aliquots of normal saline resulted in recovered lavage fluid that became progressively bloodier with each recovered aliquot. Autopsy and bronchoalveolar lavage in these patients revealed no pathogens that accounted for the clinical findings. Since the later aliquots sample predominantly alveolar material, this syndrome was termed diffuse alveolar hemorrhage (DAH). DAH was associated with a high inpatient mortality rate (23 of 29 died versus 14 of 112 without DAH, p less than 0.001) and was associated with age over 40 years, solid malignancies, high fevers, severe mucositis, white blood cell recovery, and renal insufficiency (p less than 0.05, compared with patients without DAH). However, DAH was not associated with prolonged prothrombin or partial thromboplastin times or decreased platelet counts compared with patients without DAH. CONCLUSION: DAH is a frequent cause of respiratory compromise and a major cause of mortality in autologous bone marrow transplant recipients.

Adult↗
PubMed1989

Acute antidepressant effect of lithium is associated with fluctuation of calcium and magnesium in plasma. A double-blind study on the antidepressant effect of lithium and clomipramine.

In a double-blind study on 22 patients with major depressive disorder the effects of lithium and clomipramine on signs and symptoms and on calcium and magnesium in plasma were compared. Ratings of antidepressant and side effects were performed by 2 psychiatrists at the end of a placebo period of 5-7 days and after treatment for 2 and 4 weeks. Psychopathology was rated by 15 reported and 4 observed items from the Comprehensive Psychopathological Rating Scale (CPRS). Eleven items present in 72-100% of the patients were used to evaluate the effect of the two drugs. After 2 weeks of treatment the rated scores dropped for more than half of the CPRS items. After 4 weeks the scores for all but one item were reduced in both groups. The sums of scores were significantly reduced after 2 weeks in both groups and after 4 weeks global scores were reduced as well. The drugs had notable and similar antidepressant effects. Lithium treatment was associated with fluctuations in calcium and magnesium levels in plasma not seen during clomipramine treatment. Serum prolactin increased during clomipramine treatment but was unaffected by lithium treatment. No correlations were found between the sum of rating scores and blood levels of drugs, prolactin, calcium or magnesium.

Adult↗
PubMed1989

Calcium and magnesium concentrations in affective disorder: difference between plasma and serum in relation to symptoms.

Morning (0800) plasma and serum and mean diurnal (24-h) serum calcium (Ca) and magnesium (Mg) concentrations were investigated in 56 depressed patients, 32 with acute major depression, 26 of these restudied in remission, 24 patients with longstanding depression, mainly treated with lithium, and in 27 healthy controls. All subjects were rated with the Comprehensive Psychopathological Rating Scale (CPRS). Significant differences between the groups were found for 0800 and 24-h serum Ca and Mg, 0800 plasma Mg, but not for 0800 plasma Ca. Elevations of serum Ca and Mg, plasma Mg but not plasma Ca were noted in the lithium-treated patients. Sex differences for plasma but not serum levels were seen in remission and in the controls. Depressive symptoms were negatively correlated to 0800 plasma Ca in the acute state and positively to 0800 and 24-h serum Ca and Mg in remission and longstanding depression. This difference between plasma and serum in relation to symptoms could reflect a change in a calcium binding factor present in plasma but not in serum, connected with biological factors of affective disease.

Adult↗
PubMed1989

Bronchial epithelial cells release chemotactic activity for lymphocytes.

Lymphocytes can frequently be observed in association with bronchial tissues. One mechanism that might account for this association is that bronchial epithelial cells might release chemotactic factors for lymphocytes. To test this hypothesis, bovine bronchial epithelial cells were cultured in serum-free media, and the supernatant fluids were harvested and evaluated for lymphocyte chemotactic activity using a blind-well chamber technique. Media alone attracted few lymphocytes (12 +/- 2 cells/high power field), but in contrast, there was a significant increase in the number of cells attracted by supernatant fluids obtained from bronchial epithelial cell cultures (40 +/- 6 cells/high power field, P = 0.002). The activity was dose dependent and was demonstrated to be chemotactic activity by checkerboard analysis. Partial characterization of the activity revealed it was not extractable into ethyl acetate but was partially inactivated by trypsin and heat (100 degrees C, 15 min). The responding cells were predominantly T-helper lymphocytes as shown by monoclonal antibody staining, with a smaller proportion being B-lymphocytes. Molecular sieve column chromatography revealed multiple peaks of lymphocyte chemotactic activity, with three of the peaks preferentially attracting T-helper lymphocytes and one of the peaks preferentially attracting B-lymphocytes. These data demonstrate that bronchial epithelial cells can release chemotactic factors for lymphocytes and suggest that bronchial epithelial cells may modulate their local population of immune effector cells.

Animals↗