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Biomedical subjects

L Pedersen

Publications and source records attributed to L Pedersen.

At least 109 records · Page 6Linked to original sources
PubMed1988

Effect of calcium (II) and magnesium (II) ions on the 18-23 gamma-carboxyglutamic acid containing cyclic peptide loop of bovine prothrombin. An AMBER molecular mechanics study.

The effect of calcium (II) and magnesium (II) ions on the conformation of the 18-23 cyclic peptide loop of bovine prothrombin are investigated by the molecular mechanics program AMBER (Assisted Model Building with Energy Refinement). The work is an extension of an earlier paper (Eastman et al., Int. J. Peptide Protein Res. 27, 1986, 530-553) that employed the program ECEPP (Empirical Conformational Energy Program for Peptides). In the absence of either metal ion, or in the presence of either one Ca(II) or one Mg(II) ion, the lowest-energy forms found by AMBER have the Gla21-Pro22 peptide bond in a trans conformation. In the presence of two Ca(II) or Mg(II) ions, the loop form of lowest energy is decidedly cis. The coordination about the Ca(II) and Mg(II) ions is different in both the single and double metal cases. In addition, the peptide chains that emerge from the loop are oriented parallel to each other in the lowest-energy complex with two Ca(II) ions, but are not parallel in the lowest-energy complex with two Mg(II) ions.

1-Carboxyglutamic Acid↗
PubMed1987

Combined treatment of advanced malignant melanoma with coumarin and cimetidine. A phase II study.

Immunostimulant therapy with coumarin and cimetidine was evaluated in 17 patients with advanced malignant melanoma. Induction therapy with coumarin 100 mg daily was given for 8 weeks, whereupon cimetidine 1000 mg daily was added. No patients had been previously treated with cytotoxic drugs, and all patients had a good performance status. In 16 patients progressive disease was observed, and only 1 patient experienced no change in condition, lasting 30 weeks. We conclude that treatment with this schedule of coumarin and cimetidine is without effect in advanced malignant melanoma.

Adult↗
PubMed1987

Polychlorinated biphenyls and related compound interactions with specific binding sites for thyroxine in rat liver nuclear extracts.

Thyroid hormone analogues, polychlorinated biphenyls (PCBs), and their derivatives were shown to bind specifically to thyroxine-specific binding sites in rat liver nuclear extracts. The structure-binding relationship for thyroxine binding prealbumin was qualitatively similar to that for the nuclear receptor. In general for both binding proteins, increased binding affinity was seen for the more linear and in some cases rectangular shaped (as opposed to the angular shaped thyroid hormones) chlorinated aromatic hydrocarbons with chlorine concentrated in lateral positions (3,3',5,5'-substitution on biphenyl nucleus). However two groups of compounds showed distinct quantitative differences. The relatively less polar and more lipophilic nonhydroxylated PCBs bound the nuclear receptor with significantly lower affinities while two compounds that are structurally related by the potential for equilibrium interconversion to a rigid planar structure bound with significantly higher affinities. This latter class of compounds represents soluble dioxin (TCDD) approximate isosteres and has an extended (polarizable) pi-system brought about by a planar structure (or conversion to the same) and lateral halogenation. These structure requirements are maximally expressed in 3,3',5,5'-tetrachlorodiphenoquinone (TCDQ), which shows a remarkably high affinity (Ka = 1.84 X 10(11) M-1) for the nuclear receptor. Thus, the nuclear receptor shows the expected structural specificity and sensitivity for possible involvement in the high toxicity of these classes of compounds. The physiological significance of these binding results is supported by the dose-dependent regulation (increase) of the thyroxine nuclear receptor number by dioxin, although the mechanism responsible for this increase is not clear. The nuclear binding component was further analyzed by sucrose density gradient centrifugation and was found to have a sedimentation coefficient of 4.3 S under high salt conditions. A crude estimate of the molecular weight (45,200) was obtained from a linear plot of standard globular protein fraction number (sedimentation coefficient) vs. log molecular weight. Although direct evidence is not provided, the thyroxine nuclear receptor may cooperate with a second receptor in binding the TCDQ type ligand or exists as a multimeric species with binding properties of both prealbumin and the dioxin (or Ah) receptor.

Animals↗
PubMed1986

Fine needle aspiration and Tru-Cut biopsy in the diagnosis of soft tissue metastases in breast cancer.

Soft tissue is a common site of the first recurrence in patients with breast cancer, and soft tissue lesions are often used to assess the efficacy of systemic therapy. It is therefore desirable to obtain histological/cytological verification of such lesions. It is our experience that FNA and TCB in psycho-social respects are superior to a surgical biopsy. Using a surgical biopsy as the key-diagnosis we have compared the diagnostic value of Fine-Needle Aspiration (FNA), Tru-Cut Biopsy (TCB) and clinical evaluation. The FNA was found to be significantly better than TCB in establishing the diagnosis. The diagnostic specificity and sensitivity for FNA was 1.0 and 0.65, while the corresponding figures for TCB and the clinical diagnosis were 1.0 and 0.36 and 0.76 and 0.33, respectively. Since no false positive results were obtained by use of FNA, this procedure seems to be a sufficient diagnostic procedure. However, in case of a negative outcome of the FNA, the diagnosis must be obtained by a surgical biopsy.

Adult↗
PubMed1986

Combined cytotoxic and endocrine treatment of postmenopausal patients with advanced breast cancer: preliminary results of a phase II study of the combination of prednimustine, novantrone, methotrexate, 5-fluorouracil, and tamoxifen.

Postmenopausal patients with advanced measurable and/or evaluable breast cancer entered a phase II trial of multiple agent cytotoxic therapy combined with endocrine therapy. Cycles of PNMF (prednimustine, novantrone, methotrexate, and 5-fluorouracil) were repeated every 4 weeks as follows: P, 100 mg/m2 PO on days 1 to 5; M, 40 mg/m2 IV on day 1; F, 600 mg/m2 IV on day 1, and N, 14 mg/m2 IV on day 8. The endocrine therapy was tamoxifen given continuously, 10 mg three times daily. As of May 1985, 32 eligible patients had entered the study, 20 of whom had been treated for a sufficient time to enable evaluation of response. Ten patients responded (one complete, nine partial), five experienced no change, and five patients experienced progressive disease. The treatment regimen was fairly well tolerated, the dose-limiting factor being the hematologic toxicity. Conclusions from the trial must await the inclusion of more patients and longer time of follow-up.

Adult↗
PubMed1985

Subtyping of haptoglobin--presentation of a new method.

A method is described for large scale routine phenotyping of haptoglobin (Hp) which allows complete subtyping without prior purification of the Hp molecule. The procedure includes polyacrylamide gel isoelectric focusing of reduced, neuraminidase treated serum or plasma samples, and nitrocellulose blots developed with the immunoperoxidase technique. Different variables including sample treatment, electrofocusing, blotting procedures, and immunoperoxidase visualization are discussed. Characteristic alpha-chain patterns allow identification of the common allotypes 2FS, 2SS, 2FF, IS, IF, and Johnson. Isoelectric variations in the beta-chain may also be recognized. For comparison, two-dimensional Hp-patterns are presented. The results from concurrent typing of 600 samples by ordinary starch gel electrophoresis and by the described isofocusing technique, are evaluated.

Electrophoresis, Polyacrylamide Gel↗
PubMed1985

Endocrine treatment with anti-estrogen, anti-androgen or progestagen of advanced malignant melanoma: three consecutive phase II trials.

Malignant melanoma is generally considered as a hormone-independent tumour. However, epidemiological, clinical and experimental data suggest that steroid hormones can influence the growth of this tumour. The therapeutic efficacy of endocrine treatment was evaluated in three consecutive phase II trials with the anti-estrogen tamoxifen, the anti-androgen cyproterone acetate and the progestagen medroxyprogesterone acetate. The 53 evaluable patients were mainly untreated with other forms of systemic therapy. Using response criteria in accord with WHO, none of the patients in the three trials obtained an objective remission. In summary, the present trials have demonstrated that the clinical course of advanced malignant melanoma is indifferent to competitive and additive endocrine treatment.

Adult↗
PubMed1985

Conformational properties of molecules by ab initio quantum mechanical energy minimization.

The recent literature on the determination of minimum energy conformations by ab initio quantum mechanical techniques is reviewed. The availability of computer-coded analytical first and second derivatives of the Hartree-Fock energy makes possible calculations that will be of significant assistance in structure determination of molecules. A short review of recent progress in empirical energy minimization and molecular dynamics is provided.

Models, Chemical↗
PubMed1981

Visual, auditory and somatosensory pathway involvement in hereditary cerebellar ataxia, Friedreich's ataxia and familial spastic paraplegia.

Pattern-reversal visual, auditory and somatosensory evoked potentials were recorded from 11 patients with hereditary cerebellar ataxia, 13 with familial spastic paraplegia and 7 with Friedreich's ataxia. In all the 31 patients the conduction velocity along the median and tibial nerves to the level of the spinal cord was normal. Five of the 7 patients with Friedreich's ataxia had reduced sural nerve sensory potentials. There was electrophysiological evidence of malfunction along one or several pathways within the CNS in 8 of the 11 patients with cerebellar ataxia, 4 of the 13 with familial spastic paraplegia, and in all 7 cases of Friedreich's ataxia. The increase in latency of visual, auditory and somatosensory evoked cortical potentials is attributed to nerve fibre loss in the central pathways with associated slowing of conduction.

Adolescent↗
PubMed1980

Hereditary ataxia in a large Danish pedigree.

A Danish pedigree with olivo-ponto-cerebellar ataxia, transmitted as an autosomal dominant trait through six generations, has been studied. Forty-nine individuals were affected, and the main signs were staggering, ataxic gait, dysmetria and dysarthria. Early symptoms were always imbalance and clumsiness. Clinical features varied greatly, and many types of heredo-familial ataxia had previously been assigned to the family members. Ten had been diagnosed as having multiple sclerosis (MS), although symptoms typical of MS, such as paresthesias, mental disturbances and optic atrophy were extremely uncommon. The variations in the clinical picture show that the manifestations of a single dominant gene may appear to mimic different clinical entities unless the genetic evidence is taken into account.

Adolescent↗