Thrombomodulin staining of mesothelioma cells.
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Biomedical subjects
Publications and source records attributed to R Schaefer.
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Thrombomodulin (TM) is a glycoprotein of molecular weight 75,000 kd that is normally present in restricted numbers of cells, including endothelial and mesothelial cells. In this study, the authors tested the possibility of using anti-TM to facilitate the diagnosis of mesothelioma. All of the 31 mesotheliomas and the two mesothelioma cell lines (MS-1 and MS-2) tested were stained positively with anti-TM. The specificity of anti-TM staining in mesothelioma cells was further confirmed by in situ hybridization of MS-1 cells with a TM-specific probe. The expression of TM in MS-1 cells was increased markedly when these cells were induced by 12-0-tetradecanyl phorbol 13-acetate (TPA) to differentiate. The expression of TM in mesothelioma cells, however, did not correlate with any particular phase of the cell cycle. In an attempt to differentiate pleural mesothelioma from pulmonary adenocarcinoma, the authors compared the expression of TM, carcinoembryonic antigen (CEA), and Leu M1 in these two types of tumors. Only four of 48 (8%) pulmonary adenocarcinomas were stained positively by antibodies to TM. Therefore, immunohistochemical staining with antibodies to TM yielded 100% sensitivity and 92% specificity for diagnosis of mesothelioma. All of the mesotheliomas stained negatively for CEA and Leu M1, except for one, which showed minimal focal positivity for Leu M1. In contrast, 79% and 60% of adenocarcinomas stained positively for CEA and Leu M1, respectively. These findings suggest that immunocytochemical staining with anti-TM should be added to the battery of tests to increase the diagnostic sensitivity and specificity for differentiating mesothelioma from pulmonary adenocarcinoma.
The clinical value of phospholipase measurements in serum is as yet an open question, particularly with respect to the prognosis quoad vitam. Sensitivities and specificities at different decision levels for unselected intensive care patients are reported and discussed.
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Cushing's group, operating on metastatic brain tumors in the 1920s, was the first to point out that lung cancer (usually adenocarcinoma in an upper lobe) was the most common primary tumor. Excision of a solitary metastasis could result in long-term survival. Magilligan and coworkers (J Thorac Cardiovasc Surg 1976;72:690) introduced the modern era of large series of combined lung-brain resection with low mortality (3%) and a 5-year outcome of 21%. Our results (92 patients) confirm their experience. Presenting symptoms were pulmonary (53), synchronous (28), or neurologic (11). Nonsquamous cell (48) predominated. Pulmonary resections (45) were pneumonectomy (five), lobectomy (27), segmentectomy (five), and wedge biopsy (eight). Craniotomy (68) and irradiation resulted in recurrence in seven patients. There was no operative mortality. The survival rate after curative lung and brain resection (27) was 52% at 1 year, 35% at 2 years, and 21% at 5 years. Median survival in noncurative combined resection (eight), craniotomy only (27), thoracotomy only (eight), or no surgery (22) groups, with or without irradiation or chemotherapy, averaged 6.4 months. Every effort should be made to give patients with this syndrome the benefit of combined surgery, which was not offered or agreed on in more than a third of our cases.
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We analyzed 384 veterans who had "curative" (sometimes conservative) resection from 1966 through 1986 for stage I, non-small-cell primary lung cancer to identify significant variables influencing survival. Operative mortality was 3.1%, mainly from heart attacks. Most patients were asymptomatic, presenting with other diseases of smoking. Five-year survival was 43%; deaths from lung cancer only, 63% (T1, 73%; T2, 49%). Two hundred fourteen (57.5%) of the 372 operative survivors had T1 and 158 (42.5%) had T2 disease. Sixty-five percent had peripheral nodules (84%, T1; 38% T2). Pure squamous cell predominated, in 63% overall (T1, 55%; T2, 74%). Systemic metastases caused most cancer deaths. Within T1, diameter was highly significant. Cell type and time of operation (before or after Dec 31, 1980) were also significant. Under T2, only scarring and differentiation were significant. Veterans in this group live longer if they have small squamous cell tumors.
The transformed phenotype of rat FE-8 cells transfected by an activated human HRAS gene was suppressed upon fusion with normal cells. An experimental approach was developed to identify and isolate a human gene capable of suppressing the transforming activity of the HRAS oncogene in FE-8 cells. Genomic DNA from human placenta was introduced into FE-8 cells by cotransfection with the plasmid pY3 conferring hygromycin B resistance. Transfectants were selected in medium containing hygromycin B. HRAS-transformed FE-8 cells showed an increased sensitivity toward ouabain when compared to their normal counterparts. Therefore, the population of transfected hygromycin B-resistant cells was treated with ouabain to eliminate cells with a transformed phenotype. Ouabain selection resulted in a small number of cell clones exhibiting a more normal phenotype. The clones had lost the morphology of transformed cells and required anchorage for growth. The tumorigenicity of transfectants in nude mice was reduced but not completely abolished. FE-8 revertants continued to express the p21 RAS protein. Human repetitive sequences contained in the DNA of a secondary transfectant were used for isolation of the suppressor gene from reverted FE-8 cells. The cloned DNA fragment was transfected into tumorigenic FE-8 cells and conferred a partial reversion of the transformed phenotype.
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In the study reported here the incidence and significance of translocations in antenatal diagnosis are described with reference to data of the cytogenic laboratory of Cologne University Gynecological Clinic. During the last 10 years 19 translocations were found in 4532 amnion cell cultures (0.44%), without exception in single pregnancies. In 18 cases the chromosome aberrations were balanced, i.e., the location of the genetic material was changed without loss or addition of parts of chromosomes. In one case the diagnosis of an unbalanced translocation in the form of a translocation mongolism led to termination of pregnancy. All of the other pregnancies were continued to term. Phenotypically and clinically the children were normal. The translocations were inherited in 78.9% (n = 15; 11 from the mother, 4 from the father), and de novo in 21.1% (n = 4). The results are in agreement with those of the DFG study, which identified 0.66% translocations in over 10,000 antenatal diagnoses. Of the balanced chromosome aberrations all of the newborns but one were clinically and phenotypically healthy. In cases of inherited translocations in particular, no increase in risk to the child could be determined. In cases of de novo chromosome aberrations there is a slight increase in the residual risk due to loss of minute portions of the gene. With careful technique this risk may be assumed to be very slight, so that in such cases also there is no indication for termination of pregnancy.
Color-coded computer graphics representations of the electrostatic potentials of trypsin, trypsin-inhibitor, prealbumin and its thyroxine complex, fragments of double-helical DNA, and a netropsin--DNA complex illustrate the electrostatic and topographic complementarity in macromolecule-ligand interactions. This approach is powerful in revealing intermolecular specificity and shows promise of having predictive value in drug design.
Myelin membranes purified from bovine brain are shown to form membrane vesicles when incubated in hypotonic buffer. Following restoration of isotonicity a resealing of the membrane occurs as judged by a significant decrease in 22Na+ permeability. Electron spin resonance measurements using stearic acid spin label I indicate a small decrease in membrane fluidity with increasing ionic strength between 50 and 80 mM NaCl. Iodination of myelin membrane vesicles by lactoperoxidase shows a four-fold increase in the amount of iodine incorporation into the myeline basic protein from 0--150 mM NaCl, while the iodination of the proteolipid protein remains essentially unaffected by the change in ionic strength. This dependence of the iodination of the myelin basic protein on the ionic strength can be explained by the electrostatic interactions of this protein with membrane lipids. In view of striking analogies with studies on model membranes correlating protein binding with membrane permeability changes, we suggest a similar structure-function relationship for the myelin basic protein.
Recent findings indicate that the presence of formant transitions aids the perception of the order of stimuli in repeating sequences of vowels or consonant-vowel (CV) syllables. In this study, 12 listeners reported the perceived order of four vowels or CVs in repeating sequences. Stimuli ranged in duration from 75 to 300 msec in 25-msec steps. Four stimulus sequences were used (1) varying vowels (Vv), (2) CVs with varying consonants but a constant vowel (CvVc), (3) CVs with a constant consonant but varying vowels (CcVv), (4) CVs with consonants and vowels varying (CvVv). Percentage of correct identification of order was significantly higher and mean threshold duration significantly lower for the CvVv and CvVc conditions than for the Vv condition. Mean number of sequences per response was significantly smaller for the CvVv condition than for the other conditions. Threshold durations ranged from 100 msec for the CvVv sequences to 135 msec for the Vv sequences. Ordering performance was nearly perfect for stimulus durations of about 225 to 250 msec. The results support the hypothesis that as stimuli in repeating sequences more closely resemble connected speech, listeners can more easily correctly identify the order of the stimuli.
After lobectomy a slight increase of pulmonary arterial pressure can already be observed in the state of rest. The resistance of the pulmonary vessels reveals a marked dependance on the date of operation, it increases moderately on strain, but more significantly in the state of rest. At the same time cardiac output is decreased due to the exhaustion of the myocard after straining. Cardiac insufficiency developing postoperatively is due to the reduction of pulmonary hypertension. The reduction of VC and a slight increase of resistance do not cause the arterial PO2 pressure to be lowered under conditions of strain or rest.
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From 1972 to 1975, 64 genetic amniocenteses and 72 cell cultures from amniotic fluids were done for antenatal karyotyping. In 3 cases a therapeutic abortion for genetic indication was carried out. The indications for antenatal karyotyping, the technique and complications of genetic amniocentesis in early pregnancy and the methods of cell cultures of amniotic fluid are discussed. A compilation of the results of 1918 antenatal karyotypings reported in the literature shows the following probability for the presence of an unbalanced chromosomal anomaly in the fetus: in mothers over age 40 4.25%, in mothers age 35-39, 1.45%, in cases with trisomy-21 in a previous sibling 0.73%, in cases with balanced chromosomal anomalies in the parents, 15.2%. In the next few years an increase of antenatal karyotyping in the different risk groups can be expected. In the individual case the indication for genetic amniocentesis must be balanced against the risk of complications.
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