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PubMed1990

Benign nerve sheath tumors: a light microscopic, electron microscopic and immunohistochemical study of 102 cases.

One hundred and two cases of benign nerve sheath tumors (NSTs) were studied with a combined approach using routine light microscopy (LM), immunohistochemistry (IH) for myelin basic protein (MBP) and S-100 protein as well as transmission electron microscopy (TEM) with the aim of obtaining greater insight into the true nature of these neoplasms, and also to establish the importance of IH and TEM in their diagnosis. Myelin basic protein was not identified in any of these tumors, whereas S-100 protein was positive to a variable degree in both schwannomas and neurofibromas. TEM revealed that Schwann cells predominated in tumors which were strongly positive for S-100 protein and appeared as schwannomas by LM. However, neurofibromas showing a variable patchy positivity for S-100 were composed of an admixture of Schwann cells, fibroblast-like cells and intermediate cells considered to be modified Schwann cells. Perineurial cells in typical form were not seen. It is concluded that all NSTs are basically of Schwann cell origin and that the intermediate cells and fibroblast-like cells are variants of Schwann cells. The different morphological appearances and biological behaviour of schwannomas and neurofibromas may be related to some other factors like micro-environment or genetic predisposition. Further, both IH, especially for S-100 protein, and TEM play an important role in establishing their diagnosis.

Cranial Nerve Neoplasms↗
PubMed1996

Biochemical markers of myocardial damage for early diagnosis and prognosis in patients with acute coronary syndromes. Minireview based on a doctorial thesis.

In patients with suspected AMI. Monitoring of a combination of myoglobin and CK-MB or tn-T allowed ruling-in AMI within 2-3 hours and ruling-out AMI within 3-6 hours in almost all patients admitted with chest pain and a nondiagnostic ECG. This might have a large impact on the early handling and treatment of these patients. The neural network methodology, with monitoring of myoglobin, CK-MB and tn-T allowed, within the first three hours, reliable diagnosis/exclusion of AMI/MMD and prediction of infarct size in patients admitted with suspicion of AMI. The computer system was faster than clinicians. Thus, neural network methodology might be a useful support for the early assessment of patients with suspected myocardial infarction. In patients with unstable CAD. The risk of subsequent cardiac events is increased by increasing maximal levels of tn-T obtained during the initial 24 hours. Thereby a normal, a slightly elevated and a clearly elevated tn-T level identified a low, intermediate and high risk group, respectively, for MI or death. The tn-T level was an independent prognostic variable for MI or death in a multivariate analysis comparing other early available risk indicators. Furthermore, tn-T seemed to be superior to CK-MB (mass) for risk stratification. In patients able to perform a predischarge ET both the tn-T level and the ET response were independent prognostic indicators for MI or death. The combination of tn-T and the ET response allowed a further improved risk stratification. In patients with tn-T elevation at inclusion, prolonged dalteparin treatment was beneficial. However, in patients without tn-T elevation, long term dalteparin treatment had no protective effect. Thus, tn-T determination provides independent and important prognostic information in unstable CAD. In the selection of treatment strategy for the individual patient, this simple, inexpensive and early available biochemical test might be useful.

Aged↗
PubMed1989

Combining clinical and thallium data optimizes preoperative assessment of cardiac risk before major vascular surgery.

STUDY OBJECTIVE: To determine whether clinical markers and preoperative dipyridamole-thallium imaging are both useful in predicting ischemic events after vascular surgery. DESIGN: Retrospective, observational study. SETTING: University medical center. PATIENTS: Two hundred fifty-four consecutive patients referred to a nuclear cardiology laboratory before surgery. Forty-four patients had surgery cancelled or postponed after clinical evaluation and dipyridamole-thallium imaging. Surgery was not confirmed for ten. Two hundred patients receiving prompt vascular surgery were the study group. MEASUREMENTS AND MAIN RESULTS: Thirty patients (15%) had early postoperative cardiac ischemic events, with cardiac death in 6 (3%) and nonfatal myocardial infarction in 9 (4.5%). Logistic regression identified five clinical predictors (Q waves, history of ventricular ectopic activity, diabetes, advanced age, angina) and two dipyridamole-thallium predictors of postoperative events. Of patients with none of the clinical variables (n = 64), only 2 (3.1%; 95% CI, 0% to 8%) had ischemic events with no cardiac deaths. Ten of twenty (50%; 95% CI, 29% to 71%) patients with three or more clinical markers had events. Eighteen of one hundred sixteen (15.5%; 95% CI, 7% to 21%) patients with either 1 or 2 clinical predictors had events. Within this group, 2 of 62 (3.2%; 95% CI, 0% to 8%) patients without thallium redistribution had events compared with 16 events in 54 patients (29.6%; 95% CI, 16% to 44%) with thallium redistribution. The multivariate model using both clinical and thallium variables showed significantly higher specificity at equivalent sensitivity levels than models using either clinical or thallium variables alone. CONCLUSIONS: Preoperative dipyridamole-thallium imaging appears most useful to stratify vascular patients determined to be at intermediate risk by clinical evaluation. For patients with one or two clinical predictors, thallium redistribution correlates with substantial change in probability of events. For nearly half the patients, however, thallium imaging may have been unnecessary because of very high or low cardiac risk predicted by clinical information alone.

Age Factors↗
PubMed2000

Automated oxyhemoglobin dissociation curve construction to assess sickle cell anemia therapy.

Oxyhemoglobin dissociation curves measure the most important function of red blood cells - the affinity for oxygen and its delivery to the tissues. This function may be deranged in sickle cell anemia and some other hemoglobinopathies. An automated oxyhemoglobin dissociation curve analyzer constructed dissociation curves in 55 patients with hemoglobinopathies and in 24 control subjects while maintaining constant temperature and pH. Sigmoid curves were converted to rectilinear ones using the Hill equation. Oxygen affinity of red cells was assessed by calculation of P50 (the PO2 at which hemoglobin is half saturated). Results revealed separation of oxyhemoglobin dissociation Hill plots according to phenotype but with wide variability. Mean oxygen affinity of fetal hemoglobin was greatest, whereas that of sickle hemoglobin was least. Other hemoglobins were intermediate. A positive correlation between decreased oxygen affinity and carboxyhemoglobin confirmed the decreased oxygen affinity of sickle hemoglobin and decreased oxygen affinity and increased diphosphoglycerate in red cells. Hill plots are less sensitive discriminators of oxygen affinity than traditional sigmoid dissociation curves and offer no particular advantage. Serial studies in a subset of three sickle cell anemia patients treated conservatively suggest automated oxyhemoglobin dissociation curves may be useful in assessment of effectiveness of newer therapies of sickle cell anemia after refinement of the method and studies of larger populations.

Adult↗
PubMedDate not supplied

Topoisomerase I-DNA covalent complexes in human colorectal cancer xenografts with different p53 and microsatellite instability status: relation with their sensitivity to CTP-11.

The topoisomerase I poison CPT-11 has proved efficient for the treatment of untreated metastatic colorectal cancers (CRC) and those refractory to fluoropyrimidines. However, the interpatient variability is important. A previous in vitro study suggested that measurements of the level of topoisomerase I-DNA intermediates trapped by camptothecin may be useful to estimate the chemosensitivity of colon carcinoma cell lines. To verify this hypothesis, we developed an immuno-assay to detect covalent topoisomerase I-DNA complexes in a series of human colorectal cancers xenografted in nude mice. Six human CRCs were selected for their distinctive p53 and microsatellite instability (MSI) status. Tumour lysates, prepared from mice untreated or treated with CPT-11, were fractionated onto CsCl gradients to separate free and DNA-bound topoisomerase I by centrifugation. Interestingly, significant levels of DNA-topoisomerase I complexes were detected in the tumours most responsive to the treatment with CPT-11, irrespective of their MSI and p53 phenotypes. Our in vivo study fully agrees with the predictions from the in vitro data indicating that evaluation of topoisomerase I-DNA complexes would be useful to predict the response of CRC to a treatment with CPT-11.

Animals↗
PubMed2005

A clinical and immunohistochemical study of gastrointestinal stromal tumours.

AIM: To study the clinical features, histology and immunohistochemical properties of gastrointestinal stromal tumours (GISTs); and establish any parameters that can help prognosticate the malignant potential. METHODS: Twenty-six patients with GISTs who were seen in Sultanah Aminah Hospital Johor, Malaysia from 1999 to 2003 were selected for study. Patient, clinical characteristics and outcome based on surgical records were analysed. Tumour variables (tumour size, cellularity, mitotic count, necrosis and haemorrhage) were compared between very low to low risk groups and intermediate to high risk groups. The immunohistochemical properties of GISTs were also studied. RESULTS: Patients with GISTs presented mainly with pain, palpable mass or gastrointestinal tract bleeding. The tumours were seen in stomach (50%) followed by small intestine (38.5%) and rectum (11.5%). In the period of study, six patients had metastasis, mainly in the liver or peritoneum. Immunoreactivity for CD117, CD34, vimentin, S100, neuron specific enolase, alpha-smooth-muscle-actin and desmin were observed in 100%, 76.9%, 61.5%, 46.1%, 80.8%, 11.5% and 0% of tumours respectively. The behaviour of GISTs was largely dependent on tumour size and number of mitosis. Necrosis and haemorrhage were seen in tumours with high risk potential.

Actins↗
PubMed1990

Cervical spine motion in the sagittal plane (I) range of motion of actually performed movements, an X-ray cinematographic study.

A fast method has been developed to determine the position of the outlines of bony structures on X-ray photographs of the cervical spine movements in the sagittal plane (105 mm spot film camera; 4 frames per second; about 10 seconds per complete anteflexion-retroflexion or vice versa). This method corrects for incongruity of the vertebral contours on consecutive frames due to motion in another than the sagittal plane. It also automatically corrects erroneously marked points. This method has been used to determine segmental range of motion (SROM) and total range of motion of the head with respect to the seventh cervical vertebra (TROM). It is shown that SROM may be larger when frames of intermediate instead of extreme positions of the film are considered. In ten test persons without cervical complaints the interindividual variability of SROM turned out to be comparable to the ones found with older methods. Intraindividual variability of SROM and TROM was determined by registration at three different measuring sessions (0, 2 and 10 weeks). This intraindividual variability is high, especially in the cranial and caudal parts of the cervical spine. It is concluded that SROM and TROM are unsuitable to be used as a parameter of cervical spine mobility.

Adult↗
PubMed1987

Oral anticoagulant therapy control: evidence that INR expression improves the inter-laboratory comparability of results--the Bologna oral anticoagulant control exercise.

The aims of the present study were: 1) interlaboratory normalization of prothrombin time (PT) testing for anticoagulant therapy control through calibration of customary thromboplastins against international reference materials, and 2) "on field" validation of the advantages offered by expression of results as International Normalized Ratio (INR) as opposed to percentage activity. PT tests were carried out over 8 days on the same normal subjects (16) and patients on oral anticoagulants (48) in the 9 laboratories of the Bologna area. The use of customary thromboplastins and coagulometers was maintained in all labs throughout the study. The main results were: 1) the interlaboratory CV of the prothrombin ratios obtained for each sample with all customary thromboplastins (5 different brands) was 15%, but was reduced to levels of 5.8 to 8.9 when using constant thromboplastin brands and batches; 2) the International Sensitivity Index (ISI) values obtained in the different labs were only slightly influenced by the use of different coagulometers; 3) comparable ISI values were obtained through direct calibration with the international reference material and through intermediate calibration with a locally selected standard; 4) use of INR values instead of percentage activity greatly reduced interlaboratory variability and significantly improved uniformity of anticoagulation level measurements, thus reducing the possibility of erroneous prescriptions. The Bologna exercise is therefore of educational value for laboratory and community doctors of the area in understanding and accepting the INR system.

Administration, Oral↗
PubMed1984

Coronary flow reserve measured during cardiac catheterization.

The degree of arteriographically visualized narrowing in coronary arteries has been the most important criterion for evaluating coronary disease for more than 20 years. Increasing data, however, suggest that anatomy alone does not predict the physiologic consequence of individual stenoses. We have applied a new digital arteriographic method for measuring coronary flow reserve (CFR) in patients undergoing diagnostic, postbypass, and postangioplasty catheterizations. All vessels with high-grade stenoses (greater than or equal to 70%) were found to have lower CFRs than those of normal arteries (1.01 +/- 0.15 v 1.84 +/- 0.36). However, considerable CFR variability was found in vessels of lesser stenoses. Coronary arteries that had undergone successful bypass surgery or angioplasty had intermediate CFR levels (1.44 +/- 0.18 and 1.51 +/- 0.16, respectively). Our study suggests that CFR assessed during cardiac catheterization may be useful for evaluating intermediate coronary lesions and the efficacy of interventions.

Adult↗
PubMed1993

[Biology of secondary nodal follicular b-lymphomas. A patho-dynamic study].

PURPOSE: To assess the aggressivity factors and tumour prognosis in a series of non-Hodgkin lymphomas by the use of computer-quantified specific antibodies and flow cytometry. PATIENTS AND METHODS: Sixty-one cases of follicular B-cell lymphoma: 34 of the germinal centre (24 centroblastic-centrocytic, CB-CC, and 10 centroblastic, CC) and 27 of the follicular cortex (FCL), were studied. All the cases had been diagnosed between 1971 and 1992 at the Pathology Department of the Fundación Jiménez Díaz. Morphologic and immunophenotype diagnosis was made on each case. Tumour proliferation studies were performed after labelling nuclei with proliferent nucleic acid-associated protein (PC 10); the positive nuclear areas were later quantified in a CAS-200 image analyser by means of proliferation programmes (PI) and nuclear receptors (ER). A flow cytometry study of ploidy was carried out on each case. The values attained were correlated with survival in months. The Wilcoxon's test for independent variables was used for the statistical study. RESULTS: The PI programme showed lowest proliferation for FCL (7.4%) followed by intermediate proliferation in CB-CC (16.9%) and high proliferation in CB (31.7%). The PC-10 results attained with both PI and ER programmes showed statistically significant correlation (p < 0.01). The correlation between ploidy, as quantified by flow cytometry, and survival showed statistically significant differences between diploid and aneuploid cases (p < 0.01); similar findings apply for diploids and diploids with high synthesis phase (p < 0.01). CONCLUSION: These findings support the usefulness of cell kinetics studies in lymphoma, and contribute to validate different evolutive patterns in accordance with the histologic subtype.

Biomarkers, Tumor↗
PubMed1993

[Comparative hierarchic structure of the genetic language].

The genetical texts and genetic language are built according to hierarchic principle and contain no less than 6 levels of coding sequences, separated by marks of punctuation, separation and indication: codons, cistrons, scriptons, replicons, linkage groups, genomes. Each level has all the attributes of the language. This hierarchic system expresses some general properties and regularities. The rules of genetic language being determined, the variability of genetical texts is generated by block-modular combinatorics on each level. Between levels there are some intermediate sublevels and module types capable of being combined. The genetic language is compared with two different independent linguistic systems: human natural languages and artificial programming languages. Genetic language is a natural one by its origin, but it is a typical technical language of the functioning genetic regulatory system--by its predestination. All three linguistic systems under comparison have evident similarity of the organization principles and hierarchical structures. This argues for similarity of their principles of appearance and evolution.

Genetic Code↗
PubMed1998

[Current principles of diagnosis and treatment of chronic lymphocytic B-cell leukemia].

Chronic lymphocytic leukaemia is the most frequent form of malignant hematological diseases in the Western countries, it comprises 30-40% of all the leukaemias and it manifests itself between 60-65 years of age. Clinical features are caused in 93% of the cases by the accumulation and proliferation of immunologically incompetent, anergic, long lived, CD5 positive B-lymphocytes, expressing monoclonal IgM or IgD immunglobulin, in the bone marrow, the peripheral blood, the lymphoid and in other organs. In the etiology genetic basis is highly supposed, whereas affect of toxic agents and radiation exposure can be neglected. The prognosis of patients is variable and is determined by the clinical stage and the proliferative activity of the disease. Treatment is indicated in intermediate and high-risk clinical stages only with signs of disease activation on the basis of individual patient's risk. As first line treatment, Chlorambucil is indicated in high doses. Results achieved by combined chemotherapy are generally not superior compared to high-dose Chlorambucil treatment. For patients who developed resistance to alkilating agents purin analogues are recommended. Out of them the most favorable results had been accumulated with Fludarabine as second line treatment. For minority of the cases hemopoetic stem cell transplantation as the only curative therapeutic measure is being introduced in an increasing number. This review gives an account of the recent advances in the diagnosis and therapy of the disease.

Alkylating Agents↗
PubMed2003

Variability in factor VIII concentrate measurement: results from SSC field collaborative studies.

Seven 'field' collaborative studies on factor (F)VIII concentrate potency measurements were carried out, using local routine methodology, standards and calculation of results. Data from five of the 12 different concentrates studied are described in detail. These studies revealed that, for the intermediate-purity and the recombinant FVIII concentrates, one-stage potencies were significantly lower than chromogenic potencies, whilst for the two high-purity FVIII concentrates one-stage potencies were significantly greater than chromogenic potencies. On comparing predilution methods for the intermediate-purity concentrate, equivalent potencies were obtained using either buffer or FVIII-deficient plasma as prediluent. For the two high-purity and the recombinant concentrates, potencies obtained using buffer as prediluent were significantly greater and lower, respectively, than potencies obtained using FVIII-deficient plasma as prediluent. Interlaboratory variabilities were compared over all 12 concentrates studied and coefficients of variation (CVs) for one-stage assays were found to be much greater than for chromogenic assays. This was true for all concentrates except for the intermediate-purity concentrate and samples A and B from the first study, where the reverse was true. Furthermore, much better CVs were obtained when using FVIII-deficient plasma than when using buffer as prediluent, for all FVIII concentrates except for the intermediate-purity concentrate where the reverse was true, and sample B where CVs were equivalent. Overall, CVs were far worse than those obtained in controlled collaborative studies. Generally, however, CVs were better with chromogenic assays and predilution in FVIII-deficient plasma, as is recommended by the International Society on Thrombosis and Haemostasis/Scientific and Standardization Committee, particularly for higher purity and recombinant concentrates.

Chromogenic Compounds↗
PubMed2004

In vitro assembly properties of mutant and chimeric intermediate filament proteins: insight into the function of sequences in the rod and end domains of IF.

The factors and mechanisms regulating assembly of intermediate filament (IF) proteins to produce filaments with their characteristic 10 nm diameter are not fully understood. All IF proteins contain a central rod domain flanked by variable head and tail domains. To elucidate the role that different domains of IF proteins play in filament assembly, we used negative staining and electron microscopy (EM) to study the in vitro assembly properties of purified bacterially expressed IF proteins, in which specific domains of the proteins were either mutated or swapped between a cytoplasmic (mouse neurofilament-light (NF-L) subunit) and nuclear intermediate filament protein (human lamin A). Our results indicate that filament formation is profoundly influenced by the composition of the assembly buffer. Wild type (wt) mouse NF-L formed 10 nm filaments in assembly buffer containing 175 mM NaCl, whereas a mutant deleted of 18 NH2-terminal amino acids failed to assemble under similar conditions. Instead, the mutant assembled efficiently in buffers containing CaCl2 > or = 6 mM forming filaments that were 10 times longer than those formed by wt NF-L, although their diameter was significantly smaller (6-7 nm). These results suggest that the 18 NH2-terminal sequence of NF-L might serve two functions, to inhibit filament elongation and to promote lateral association of NF-L subunits. We also demonstrate that lengthening of the NF-L rod domain, by inserting a 42 aa sequence unique to nuclear IF proteins, does not compromise filament assembly in any noticeable way. Our results suggests that the known inability of nuclear lamin proteins to assemble into 10 nm filaments in vitro cannot derive solely from their longer rod domain. Finally, we demonstrate that the head domain of lamin A can substitute for that of NF-L in filament assembly, whereas substitution of both the head and tail domains of lamins for those of NF-L compromises assembly. Therefore, the effect of lamin A "tail" domain alone, or the synergistic effect of lamin "head" and the "tail" domains together, interferes with assembly into 10-nm filaments.

Amino Acid Sequence↗
PubMedDate not supplied

Risk factors, confounding, and the illusion of statistical control.

When experimental designs are premature, impractical, or impossible, researchers must rely on statistical methods to adjust for potentially confounding effects. Such procedures, however, are quite fallible. We examine several errors that often follow the use of statistical adjustment. The first is inferring a factor is causal because it predicts an outcome even after "statistical control" for other factors. This inference is fallacious when (as usual) such control involves removing the linear contribution of imperfectly measured variables, or when some confounders remain unmeasured. The converse fallacy is inferring a factor is not causally important because its association with the outcome is attenuated or eliminated by the inclusion of covariates in the adjustment process. This attenuation may only reflect that the covariates treated as confounders are actually mediators (intermediates) and critical to the causal chain from the study factor to the study outcome. Other problems arise due to mismeasurement of the study factor or outcome, or because these study variables are only proxies for underlying constructs. Statistical adjustment serves a useful function, but it cannot transform observational studies into natural experiments, and involves far more subjective judgment than many users realize.

Bias↗
PubMed1991

Virucidal efficacy of saturated intermediate length straight-chain alcohols in biologically active protein solutions.

Manufacturing processes for therapeutic products derived from recombinant DNA and hybridoma technology have required a re-assessment of the parameters traditionally applied for inactivation of endogenous viruses. Historically, time, temperature and concentration of the virucidal agent were the variables considered, whereas pH and ionic environment were restricted by physiological concerns to neutral pH and isotonic buffered solutions. Newer processes are less restrictive of pH and ionic environment, and this has permitted exploration of a wider range of virucidal agents and conditions. Intermediate length straight-chain alcohols are highly virucidal at low pH, with diminished activity at higher pH. Decreased activity was demonstrated by derivatives of the alcohols depending on the position of the hydroxyl group. Applications to proteins include monoclonal antibodies.

Alcohols↗
PubMed1986

Relationship of angiographically defined coronary artery disease to serum lipoproteins and apolipoproteins in young survivors of myocardial infarction.

The relationship of serum lipoprotein and apolipoprotein concentrations to angiographically determined coronary artery disease was investigated in 105 consecutive male survivors of myocardial infarction under the age of 45. Concentrations and composition of lipoproteins, lipid indexes, and nonlipid risk factors (tobacco consumption, hypertension, reduced glucose tolerance, and obesity) were related to a recently developed scoring system for semiquantitative estimation of diffuse coronary atheromatosis, as well as to the number and severity of significant coronary artery stenoses. The concentrations of cholesterol in very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), in combination with serum triglyceride or VLDL triglyceride level, comprised the best set of independent discriminatory lipid variables between patients and control subjects. In the patients, LDL cholesterol and apolipoprotein B levels showed strong relationships to the extent and severity of coronary atheromatosis but not to the number and severity of distinct coronary stenoses. HDL2 cholesterol concentration correlated inversely with the coronary atheromatosis score, whereas other variables reflecting HDL concentration and composition or VLDL lipids were not independently related to any of the coronary scores. The LDL triglyceride level, an index of intermediate-density lipoprotein (IDL) accumulation, was significantly correlated to the coronary atheromatosis score in univariate analysis. Nonlipid risk factors were correlated neither to coronary atheromatosis nor to severity of stenoses. Stepwise multiple regression analyses of data adjusted for age, cumulative tobacco consumption, and weight indicated that 18% of the variation in the coronary atheromatosis score could be accounted for by levels of apolipoprotein B. Addition of other lipoprotein variables or the nonlipid variables hypertension and glucose tolerance did not significantly increase the value of R2. When ratios of lipoprotein lipids and apolipoproteins were included in the regression model, the highest multiple correlation coefficient was obtained with the LDL/HDL cholesterol ratio alone (R2 = .22). The present data demonstrate the importance of elevated LDL cholesterol and apolipoprotein B concentrations for the development of coronary atheromatosis in young male survivors of myocardial infarction. The lack of correlations between the levels of lipoprotein lipids and serum apolipoproteins and the severity of coronary stenoses suggests that mechanisms other than disturbances of lipoprotein metabolism may be involved in the progression of more advanced coronary lesions.

Adult↗
PubMed1992

Two-dimensional electrophoretic analysis of transformation-sensitive polypeptides during chemically, spontaneously, and oncogene-induced transformation of rat liver epithelial cells.

Recently, we described the establishment of a computerized database of rat liver epithelial (RLE) cellular polypeptides (Wirth et al., Electrophoresis, 1991, 12, 931-954). This database has now been expanded to include the analysis of cellular polypeptide alterations during chemically (aflatoxin B1; AFB), spontaneously, and oncogene (v-Ha-ras, v-raf, and v-myc/v-raf)-induced transformation of RLE cells. Two-dimensional mapping of [35S]methionine-labeled whole cell lysate, cell-free in vitro translation products and [32P]orthophosphate-labeled polypeptides revealed subsets of polypeptides specific for each transformation modality. A search of the RLE protein database indicated the specific subcellular location for the majority of these transformation-sensitive proteins. Significant alterations in the expression of the extracellular matrix protein, fibronectin, as well as tropomyosin- and intermediate filament-related polypeptides (vimentin, beta-tubulin, the cytokeratins, and actin) were observed among the various transformant cell lines. Immunoprecipitation and Western immunoblot analysis of tropomyosin expression in four individual AFB-, as well as four spontaneously induced, and each of the oncogene-transformed cell lines indicated that five major tropomyosin (Tm 1-5) isoforms were variably expressed in the various cell lines, including one polypeptide tentatively identified as Tm6. Whereas alterations in tropomyosin expression appeared to be transformation-specific, alterations in the individual intermediate filament polypeptides were related more to the differentiation state of the individual cell lines rather than to the transformation phenotype. These studies extend our earlier efforts toward the establishment of a comprehensive computerized database of RLE cellular proteins and demonstrates how such a database may serve as a useful source for studies concerning the regulation of growth and differentiation as well as transformation of RLE cells.

Actins↗