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R Michalski

Publications and source records attributed to R Michalski.

At least 19 recordsLinked to original sources
PubMed1998

DerivFit: a program for rate equation parameter fitting using derivatives.

A C program for fitting parameters in enzymatic rate equations is presented. The DerivFit program employs the reaction scheme in the form of ordinary differential equations (ODEs). The kinetic parameters are fitted to the experimental data by minimizing the sum of squared deviations of experimental points from theoretically predicted progress curves. In the minimization process we use the Gradient, Newton, and Marquardt algorithms. The gradients are calculated explicitly by solving a set of additional ODEs that are automatically attached by the program, taking advantage of a general formulation of the basic ODEs that determine the reaction's time course. The program is applied to simple enzymatic systems including slow tight-binding inhibition.

Algorithms↗
PubMed1998

Allelic losses and DNA methylation at DNA mismatch repair loci in sporadic colorectal cancer.

Normal and tumor DNA samples of 35 patients with sporadic colorectal carcinoma were analyzed for microsatellite alterations at 12 markers linked to mismatch repair loci: hMLH1, hMSH2, hMSH3, hMSH6, hPMS1 and hPMS2. Remarkably, no correlation was observed between the replication error phenotype (RER+) and allelic losses at these loci. Hemizygous deletions, seen in 6/35 (17%) informative cases at hMLH1, 4/27 (15%) at hMSH2/hMSH6 and 6/34 (18%) at hMSH3, were rarely found in RER+ tumors. Since mismatch repair protein components act in molecular complexes of defined stoichiometry we propose that hemizygous deletion of the corresponding loci may be involved in colorectal tumorigenesis through defects in cellular functions other than replication error correction. The analysis of the methylation status of the promoter region of hMLH1 revealed that methylation might be an important mechanism of this locus inactivation in RER+ sporadic colorectal cancer.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Trichinella spiralis thymidylate synthase: developmental pattern, isolation, molecular properties, and inhibition by substrate and cofactor analogues.

Thymidylate synthase specific activity was found to remain at a constant level in crude extracts from muscle larvae, isolated (1-15 months after infection) by pepsin-HCI digestion, as well as from adult worms of Trichinella spiralis. The enzyme was purified and its molecular (monomer mol. wt 35 kD) and kinetic (sequential mechanism with the K(m) values 3.1 and 19 microM for dUMP and N5,10-methylenetetrahydrofolate, respectively) properties determined. 5-Fluoro-dUMP was a competitive, slow-binding inhibitor of the parasite enzyme. N5,10-methylenetetrahydrofolate analogues 10-propargy1-5,8- dideazafolate (CB3717), ZD1694, BW1843U89, and AG337 were weaker inhibitors of the parasite than regenerating rat liver enzyme. Inhibition by 10-propargyl-5,8-dideazafolate was strengthened by an increasing number of glutamate residues. Thymidine kinase activity could not be detected in the muscle larvae crude extracts.

Animals↗
PubMed1991

Immunolocalization of prealbumin (transthyretin) in renal cell carcinoma.

Fourteen primary and nine metastatic renal cell carcinomas were examined with a commercially available antibody against prealbumin (transthyretin) using the avidin-biotin-peroxidase complex (ABC) technique. Twenty-two of the 23 tumours expressed prealbumin, and in 16 of them more than 50% of the tumour cells showed immunoreactivity. The same tumours were subjected to immunostaining with antibodies against low molecular weight keratin, carcino-embryonic antigen, S-100 protein and epithelial membrane antigen for comparison. We conclude that prealbumin, which was absent in 14 adenocarcinomas from other organs, should be included in the panel of markers for differentiating metastatic adenocarcinoma of renal origin from those of other primary tumours.

Carcinoma, Renal Cell↗
PubMed1989

Serous cystadenocarcinoma of the pancreas: a new entity?

Microcystic cystadenoma of the pancreas is a well-recognized although rare pathological entity. All previously reported examples of this tumor have been uniformly benign in behavior. In this case report, we present a primary tumor of the pancreas that was histologically indistinguishable from microcystic adenoma, but which behaved in a malignant fashion. Metastases were found in the stomach and liver. We believe that this case represents a new entity, which we have termed "serous cystadenocarcinoma of the pancreas."

Aged↗
PubMed1977

A heparin analogue with specific action on antithrombin III.

The effects of heparin and a semi-synthetic heparin analogue were compared in vivo and in vitro. The two drugs differed strikingly in their in-vitro behaviour: unlike heparin, the heparin analogue had little effect in a specific heparin assay or on overall clotting, as measured by the kaolin-cephalin clotting time (K.C.C.T.). When given by parenteral injection, the heparin analogue had almost the same potentiating effect on antithrombin III as mucous heparin, but without a comparable effect on the K.C.C.T. These observations suggest that the heparin analogue may have desirable characteristics for the prophylaxis of venous thrombosis, since it selectively potentiates antithrombin III in vivo while having little effect on overall clotting.

Adult↗
PubMed1977

Comparison of heparin and a semi-synthetic heparin analogue, A73025. I. Kinetics of clearance from the circulation of man following intravenous injection.

A study has been made of a low molecular weight semi-synthetic heparin analogue, A73025, that may be clinically useful as an antithrombotic agent because of its reported high specificity for antithrombin III. The clearance from the circulation of both heparin and the analogue has been studied in man following intravenous injection. Heparin obeyed almost first order kinetics when assayed using a specific anti-Xa assay and first order kinetics when measured with KCCT. At high concentrations the heparin analogue was cleared with first order kinetics when assayed both with the anti-Xa assay and with KCCT. At low concentrations the analogue produced between one half and two-thirds of the anti-Xa activity of an equal dose of heparin, producing only a small prolongation of KCCT. With increasing dose, the more specific anti-Xa potentiating effect of A73025 decreased because of a flattening of its anti-Xa dose-response curve. These results suggest that the analogue might be useful as an antithrombotic agent when it is used as a prophylactic agent.

Adult↗
PubMed1977

Comparison of heparin and a semi-synthetic heparin analogue, A73025. II. Some effects on platelet function.

A comparison has been made of some effects of a semi-synthetic heparin analogue, A73025, and heparin upon platelet function. In several of the in vitro tests performed, such as their potentiating effects on ADP and adrenaline induced aggregation and their effects on the aggregation of washed platelets by activated factor X, heparin proved to be more potent than A73025. Following intravenous injection of twice the quantity of A73025, an equivalent anti-factor Xa activity was obtained, in the agreement with our previous studies. However, it was found that PRP containing heparin and A73025 with comparable anti-Factor Xa acitvity responded differently to the addition of thrombin, as A73025 barely inhibited thrombin induced aggregation. Similarly, A73025 had little effect on the dilute thrombin clotting time of plasma, following intravenous injection. Heparin and A73025 were neutralized to approximately the same degree by a crude PF4 preparation.

Adenosine Diphosphate↗
PubMed1977

Occurrence of malignant neoplasms in patients with chronic lymphatic leukaemia.

In a group of 280 patients with chronic lymphatic leukaemia, a coexistence of malignant tumours diagnosed simultaneously with the leukaemia was found in 14 cases or 5.0%. No significant difference was observed between the development of the second malignant neoplasm in the patients studied and the expected incidence in the general population, taking into account also the sex and age of patients and their place of residence. No statistically significant relation was found between the duration of CLL and the occurrence of second malignancies. No significant correlation was found between the total dose of cytostatic drugs, corticosteroids or radiotherapy and the incidence of cancer.

Adult↗
PubMed1976

[To treat or not to treat chronic lymphocytic leukemias with a mild course?].

The study is based on a material of 60 patients with chronic lymphocytic leukaemia of mild course with survival over 4 years. The method used was a comparison of the patients treated from the time of diagnosis establishment with the group of similar patients not treated throughout the whole period of follow-up and with another group of patients treated from the time of exacerbation of the proliferative process. The following data were taken into account: survival length, degree of splenomegaly and lymphadenopathy, leucocyte and platelet counts, haemoglobin level, infectious complications. It was demonstrated that cytostatic and/or hormonal treatment started at the time of diagnosis establishment did not prolong the survival. A statistically significant prolongation of survival time was observed, on the other hand, in cases treated from the time of exacerbation. Cytostatic agents increased the risk of infections and the risk of thrombocytopenia.

Acute Disease↗
PubMedDate not supplied

[Course of chronic lymphatic leukemia in 2 age groups: older and younger patients].

The authors analysed 202 cases of chronic lymphatic leukaemia comparing the course of this disease in patients above and below 60 years of age. The observation included patients with various forms of this disease--with morphological and clinical findings compatible with mild disease and cases with severe course with complications. It was observed that in severe form of lymphatic leukaemia the course of the disease is similar in both groups of patients and the shorter survival of patients in the older group is frequently due to coexistence of other diseases impairing the general condition and changes connected age. On the other hand, a mild, oligosymptomatic course of the disease was observed more frequently in older patients who did not require intense treatment in hospitals.

Adult↗