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L Pedersen

Publications and source records attributed to L Pedersen.

At least 91 records · Page 5Linked to original sources
PubMed1993

Vimentin expression in 98 breast cancers with medullary features and its prognostic significance.

The expression of vimentin, as assessed by immunohistochemistry, has been evaluated in 69 medullary carcinomas of the breast: 28 typical medullary carcinomas (TMC), 41 atypical medullary carcinomas (AMC), and 29 invasive ductal carcinomas with subtle medullary features that, however, did not fulfill the strict criteria of TMC or AMC. Immunoreactivity of at least 10% of the component cells was found in 14 of the medullary carcinomas (5 out of 28 TMC, 9 out of 41 AMC whereas only 1 of the invasive ductal carcinomas was vimentin-positive. The patients were followed for 8-13 years. No difference in recurrence-free survival or overall survival could be documented between vimentin-positive and vimentin-negative carcinomas with medullary features. No biological significance could be established for vimentin labelling in these lesions.

Breast Neoplasms↗
PubMed1992

Molecular dynamics simulation of bovine prothrombin fragment 1 in the presence of calcium ions.

Early solvation-induced structural reorganization of calcium prothrombin fragment 1 is simulated with molecular dynamics. Initial coordinates are those of the 2.2-A resolution crystal structure [Soriano-Garcia, M., Padmanabhan, K., de Vos, A. M., & Tulinsky, A. (1992) Biochemistry 31, 2554-2556]. The molecular dynamics code AMBER, appropriately modified to include long-range (less than or equal to 22.0 A) ionic forces, was employed. The solution structure appears to equilibrate within 100 ps. Although minor changes are seen in various structural domains, the early solution structure basically maintains an intricate network of nine gamma-carboxyglutamic acid (Gla) residues encapsulating seven calcium ions. However, the Gla domain moves with respect to the kringle domain. This motion is mainly due to the movement of Ser34-Leu35 that appears to be a flexible hinge between the domains. The N-terminus of Ala 1 is in a tightly bound complex with three Gla residues that remains stable in the solution structure when the long-range electrostatic cutoff is employed and the near planar alignment of the seven calcium ions is only slightly distorted. The simulation structure is discussed in terms of experiments that studied calcium ion-induced quenching of the intrinsic fluorescence, protection of the N-terminal amino group from acetylation by calcium ions, chemical modification of the N-terminus to a trinitrophenyl derivative, and the possibility of a calcium-binding site(s) in the kringle domain.

Amino Acid Sequence↗
PubMed1992

Molecular cloning of osteoma-inducing replication-competent murine leukemia viruses from the RFB osteoma virus stock.

We report the molecular cloning of two replication-competent osteoma-inducing murine leukemia viruses from the RFB osteoma virus stock (M. P. Finkel, C. A. Reilly, Jr., B. O. Biskis, and I. L. Greco, p. 353-366, in C. H. G. Price and F. G. M. Ross, ed., Bone--Certain Aspects of Neoplasia, 1973). Like the original RFB osteoma virus stock, viruses derived from the molecular RFB clones induced multiple osteomas in mice of the CBA/Ca strain. The cloned RFB viruses were indistinguishable by restriction enzyme analysis and by nucleotide sequence analysis of their long-terminal-repeat regions and showed close relatedness to the Akv murine leukemia virus.

Animals↗
PubMed1991

Medullary carcinoma of the breast, proposal for a new simplified histopathological definition. Based on prognostic observations and observations on inter- and intraobserver variability of 11 histopathological characteristics in 131 breast carcinomas with medullary features.

In a previous study of 131 breast carcinomas with medullary features, we evaluated the diagnostic inter- and intraobserver variation and its prognostic implications using the criteria of typical (TMC) and atypical (AMC) medullary carcinoma of the breast put forward by Ridolfi et al. (1977). We found a considerable interobserver variation as well as intraobserver variation, with significant implication on prognosis, and concluded that the histopathological definition of MC must be sharpened and simplified in order to increase the diagnostic reproducibility. In the present study of the same population of 131 patients with breast carcinomas with medullary features we have examined inter- and intraobserver variation concerning 11 histopathological characteristics. Furthermore, we have analysed the prognostic importance of these 11 histopathological features, and the prognostic implications of the observed inter- and intraobserver variation. Based on the observations, we have eliminated criteria with poor inter-/intraobserver agreement as well as those implying no or minimal impact on the prognosis. We propose a new simplified histopathological definition of medullary carcinoma of the breast (MC), retaining reproducible, prognostically significant criteria (syncytial growth pattern and diffuse, moderate or marked mononuclear infiltration). The prognosis of MC, based on this definition, is significantly better than those of infiltrating ductal carcinomas grade II + III.

Breast Neoplasms↗
PubMed1990

Determination of transient or stable neo expression levels in mammalian cells.

We report an extension of the neomycin phosphotransferase II dot-blot assay to allow more rapid and sensitive quantitative determination of the neo gene product in crude mammalian cell extracts. Our procedure, based upon the dot-blot assay of Platt and Yang [Anal. Biochem. 162 (1987) 502-514], measures both the enzymatic activity and the protein content of a cell extract by scanning with an enzyme-linked immunosorbent assay reader, using the same sample rather than parallel samples for both measurements. We show this assay to be comparable to the chloramphenicol acetyltransferase assay in sensitivity. Therefore, apart from being a useful selectable marker gene, the neo gene is a convenient reporter gene in studies of stable, as well as transient, expression.

Animals↗
PubMed1990

[Access to case records at the County Hospital in Vordingborg].

During 1987, all requests for access to case records at the Psychiatric Hospital in Vordingborg were registered prospectively. Fifty-nine patients made a total of 69 requests for access to case records. The total time used by the staff in connection with the requests was 51 hours and 47 minutes. Of all the patients admitted to the hospital in 1987 only 3.7% asked for access to case records. No serious problems in relation to this were registered. There was a significant tendency for the younger patients, the patients with non-psychotic disorders, and especially patients with borderline disorders to ask for access to their records more frequently.

Adolescent↗
PubMed1990

Pathogenicity of BALB/c-derived N-tropic murine leukemia viruses.

N-tropic murine leukemia viruses have been observed in connection with radiation-induced osteosarcomagenesis in BALB/c mice. We have investigated the bone disease-inducing potential of molecularly cloned, BALB/c-derived N-tropic viruses in the random-bred NMRI mouse strain. The germ-line virus and an exogenous virus isolate were found to induce high incidences of osteopetrosis and lymphomas and a lower incidence of osteomas. Two viruses derived from somatically acquired proviruses of independent radiation-induced osteosarcomas induced lower incidence of osteopetrosis and lymphomas. Nucleotide sequence analysis of the long terminal repeat regions and RNase T1 fingerprint analysis revealed only few differences between the isolates. The possible involvement of N-tropic murine leukemia viruses in radiation-induced osteosarcomagenesis in the BALB/c mouse strain is discussed.

Animals↗
PubMed1990

The development of an observer-scale for measuring social dysfunction and aggression.

Scales for measuring aggressive cognitions and behaviour have mainly been administered by nursing-staff or been self-ratings. During recent years we have made an attempt to construct an observer-scale for aggression analogous to the Hamilton scale for depression. The Social Dysfunction and Aggression Scale (SDAS) consists of 9 items (SDAS-9) covering outward aggression and 2 items (SDAS-2) covering inward aggression. The inter-observer reliability of the SDAS has been found adequate in terms of intra-class coefficients. In a pilot study on 82 inpatients from different centres in Denmark and Sweden the SDAS was compared to three-item scales for outward and inward aggression and to a global scale for outward aggression. The results showed that the SDAS-9 correlated positively with the other outward observer-scales, and the SDAS-2 with the other inward scale. A divergent validity was seen between the outward and inward scales, indicating that it is necessary to measure both dimensions. Preliminary ranks-according-to-frequency scores showed the following order of the nine outward items: irritability, dysphoric mood, social disturbances, nondirected verbal aggressiveness, negativism, directed verbal aggressiveness, physical violence towards staff, physical violence towards things, and physical violence towards persons other than staff.

Aggression↗
PubMed1990

Codeine in analgesic doses does not depress respiration in patients with severe chronic obstructive lung disease.

Nineteen normocapnic patients with chronic obstructive lung disease participated in an open single dose safety study (part one) followed by a randomized double-blind cross-over study comparing two seven-days treatment periods of 1 g of paracetamol t.i.d. with 60 mg of codeine plus 1 g of paracetamol t.i.d., respectively (part two). In part one, continuous monitoring after a single dose of 2 g of paracetamol and 120 mg of codeine revealed no deterioration in the respiration and gas tensions. In part two, respiratory parameters and arterial gas tensions were recorded one hour after the last morning dose. PaCO2 increased insignificantly (0.05 less than P less than 0.10) by a median of 0.38 kPa during treatment with codeine and paracetamol compared to treatment with paracetamol alone. PaO2 decreased by 0.12 kPa (P greater than 0.10). There was no correlation between changes in PaCO2 and changes in PaO2. FVC, FEV1 and dyspnoea at rest were unchanged. Gastrointestinal side effects were reported significantly (P less than 0.02) more often during treatment with codeine plus paracetamol. There was no correlation between the plasma concentration of codeine or morphine and changes in respiratory parameters or adverse effects. The limitation for the short time clinical use of codeine as an analgesic to normocapnic patients with severe chronic obstructive lung disease in stable phase seem to be gastrointestinal side effects.

Acetaminophen↗
PubMed1990

The prognostic importance of syncytial growth pattern in medullary carcinoma of the breast.

The histopathological criteria for medullary carcinoma of the breast (MC) used by most pathologists today were delineated by Ridolfi et al. in 1977. The prime criterion is: "A predominantly syncytial growth pattern", predominantly being defined as including 75% or more of the tumour. However, no indication has been given as to why this limit was set at 75%. The present study analyzes the prognostic importance of the extent of syncytial growth in a population of 102 breast cancers with medullary features. Generally, we find a positive prognostic influence of an extensive syncytial growth. The prognostic importance of setting the limit for predominantly syncytial growth at 90% and at 75%, respectively, is evaluated. This comparative study provides no basis for changing the definition of predominantly syncytial growth pattern.

Breast Neoplasms↗
PubMed1989

Inter- and intraobserver variability in the histopathological diagnosis of medullary carcinoma of the breast, and its prognostic implications.

One hundred thirty-one breast carcinomas with medullary features, registered in the Danish Breast Cancer Cooperative Group from 1977-1982, have been histopathologically reviewed by two senior pathologists and classified as typical medullary carcinoma (TMC), atypical medullary carcinoma (AMC), and non-medullary carcinoma (NMC). Diagnostic criteria were based on those put forward by Ridolfi et al. and Fisher et al. The procedure was repeated with an interval of about one year by both pathologists. The diagnostic interobserver agreement was 72% with a Kappa of 0.55. The intraobserver agreement was 77% and 63% with Kappa values of 0.64 and 0.44, respectively. To see whether the observed inter- and intraobserver variability had any prognostic implications, diagnostic subgroups for both pathologists were analyzed with Kaplan Meier plots for recurrence-free survival (RFS) and with log rank tests. In the first evaluation pathologist 1 segregated a group of TMC with a significantly better RFS than for the NMC group, and pathologist 2 segregated a group of TMC with a corresponding strong trend. These findings could not, however, be reproduced in the second evaluation. The study indicates that the criteria of TMC and AMC as proposed by Ridolfi et al. need to be sharpened and simplified in order to reduce inter- and intraobserver variability. Larger studies with a control group of infiltrating ductal carcinomas are mandatory to elucidate the clinical importance of the diagnoses of Typical and Atypical Medullary Carcinoma of the breast.

Actuarial Analysis↗
PubMed1989

Inhibition of insulin receptor phosphorylation by peptides derived from major histocompatibility complex class I antigens.

Peptides from the alpha 1 region (residues 61-85) of the D and K molecules of the major histocompatibility complex class I antigens inhibit insulin-induced tyrosine kinase activity of the purified human insulin receptors (IRs) as measured both by autophosphorylation and IR-mediated substrate [poly(Glu,Tyr)] phosphorylation. Half-maximal effect of the Dk-(61-85) peptide on IR autophosphorylation is obtained at 1.2 microM, and almost complete inhibition of IR kinase activity is obtained at 10 microM peptide. The corresponding K kappa-(61-85) peptide has a significantly weaker effect on autophosphorylation. No such effects are observed with nine peptides of similar length, but unrelated to major histocompatibility complex class I antigens. Neither of the major histocompatibility complex class I-derived peptides has any effect on the constitutively active kinase of a genetically engineered cytoplasmic IR domain. Further, insulin binding to IR is unaltered in the presence of the major histocompatibility complex class I-derived peptides. The inhibitory activity of the peptides on insulin-induced IR phosphorylation facilitated the observation that IRs require insulin to become substrate for an independent tyrosine kinase. In the presence of an inhibitory peptide, the constitutively active cytoplasmic IR kinase domain only phosphorylates the intact IR in the presence of insulin. We conclude that the tyrosine kinase activity of IRs may be altered by peptide interaction at an allosteric site and, moreover, IRs require insulin to assume a conformation permitting phosphorylation by an independent kinase.

Allosteric Site↗
PubMed1988

Influences of solvent water on protein folding: free energies of solvation of cis and trans peptides are nearly identical.

Peptide bonds interact so strongly with water that even a modest difference between the free energies of solvation of their cis and trans isomers could have a significant bearing on protein structure. However, proton magnetic resonance studies at high dilution in deuteriated solvents show that N-methylformamide exists as the cis isomer to the extent of 8% in water, 10.3% in chloroform, 8.8% in benzene, and 9.2% in cyclohexane. Integrated intensities of proton and carbon resonances show that N-methylacetamide exists as the cis isomer to the extent of only 1.5% in water, not changing much in nonpolar solvents. Quantum mechanical calculations using the 6-31G basis set reproduce these relative abundances with reasonable accuracy and show that there is little difference between the dipole moments of the cis and trans isomers, for either amide. The remarkable insensitivity of cis/trans equilibria to the solvent environment and the heavy preponderance of trans isomers regardless of the polarity of the surroundings (ca. 98.5% for N-methylacetamide, whose properties may resemble those of a typical peptide bond) accord with the overwhelming preference of peptide bonds for the trans configuration that is consistently observed in the three-dimensional structures of globular proteins.

Acetamides↗
PubMed1988

Amplification of endogenous proviral MuLV sequences in radiation-induced osteosarcomas.

The endogenous ecotropic provirus of BALB/c mice was found to be amplified in 17 out of 29 radiation-induced osteosarcomas. In contrast, 19 clonal cell lines established from bone-marrow cells of a tumor-bearing mouse, which were used as controls, did not reveal newly acquired ecotropic proviruses. Ecotropic viral RNA was expressed in tumors that showed reintegrated proviruses. DNA probes from 2 tumors, derived from cellular sequences flanking the newly integrated proviruses, did not detect DNA rearrangements in any of the other tumors. The possible role of activated endogenous retroviruses in the development of radiation-induced osteosarcomas is discussed.

Animals↗
PubMed1988

Forensic aspects of haptoglobin: electrophoretic patterns of haptoglobin allotype products and an evaluation of typing procedure.

A procedure used for haptoglobin (Hp) typing in paternity cases has been evaluated. All serum samples have been subtyped with a one-dimensional isoelectric focusing/immunoblotting method, and samples with rare or questionable patterns have been further examined by two-dimensional electrophoresis with isoelectric focusing in the first dimension followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the second dimension. The electrophoretic Hp-patterns of common and rare alpha- and beta-chain variants are shown, including allotype patterns of two new beta-chain variants and three new alpha-chain variants. Retyping of nearly 2000 individuals at intervals between 1 to 12 months revealed a typing error frequency of about 0.3%, which is considered acceptable, provided new blood samples are required in every case of paternity exclusion. Comparison of typing results obtained with the present procedure and with routine starch gel electrophoresis in more than 5000 serum samples gave conflicting results in 6 samples. The sensitivity of the described one-dimensional subtyping method was slightly better than that of starch gel electrophoresis. In 4110 unrelated individuals, involved in cases of disputed paternity the Hp 2SS 0.038, Hp 2FF 0.004, and Hp 3 (Johnson) 0.0005. These allele frequencies give a theoretical paternity exclusion rate of 32.5%, which is in accordance with the observed rate in 2200 paternity cases with more than 600 non-fathers. It is concluded that the present procedure represents a definite improvement for Hp subtyping in practical paternity diagnostics. Preliminary results with retyping of weak Hp patterns using a staining technique involving the biotin/avidin complex indicate that the sensitivity of the one-dimensional subtyping method may be substantially increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophoresis, Gel, Two-Dimensional↗
PubMed1988

Repeated fine needle aspirations in the diagnosis of soft tissue metastases in breast cancer.

In 36 patients, treated for breast cancer and with a suspected metastasis in the subcutis, the diagnostic efficacy of repeated fine needle aspiration (FNA) has been evaluated in 39 tumours. By increasing FNA from one to three, the diagnostic sensitivity was increased from 0.59 (95% C.L. 0.33-0.82) to 0.83 (95% C.L. 0.52-0.98). Diagnostic specificity for one aspiration was 0.95 (0.77-1.00), and for two and three aspirates it was 0.96 (0.80-1.00) if suspicious aspirates were considered as positive, and 1.00 for one, two and three aspirations when only aspirates with tumour cells were considered positive. Statistically, three aspirates were significantly better than one in establishing the diagnosis of a soft tissue tumour in patients with breast cancer.

Biopsy, Needle↗