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M Makowski

Publications and source records attributed to M Makowski.

17 recordsLinked to original sources
PubMed2006

Heme oxygenase-1 protects tumor cells against photodynamic therapy-mediated cytotoxicity.

Photodynamic therapy is a promising antitumor treatment modality approved for the management of both early and advanced tumors. The mechanisms of its antitumor action include generation of singlet oxygen and reactive oxygen species that directly damage tumor cells and tumor vasculature. A number of mechanisms seem to be involved in the protective responses to PDT that include activation of transcription factors, heat shock proteins, antioxidant enzymes and antiapoptotic pathways. Elucidation of these mechanisms might result in the design of more effective combination strategies to improve the antitumor efficacy of PDT. Using DNA microarray analysis to identify stress-related genes induced by Photofrin-mediated PDT in colon adenocarcinoma C-26 cells, we observed a marked induction of heme oxygenase-1 (HO-1). Induction of HO-1 with hemin or stable transfection of C-26 with a plasmid vector encoding HO-1 increased resistance of tumor cells to PDT-mediated cytotoxicity. On the other hand, zinc (II) protoporphyrin IX, an HO-1 inhibitor, markedly augmented PDT-mediated cytotoxicity towards C-26 and human ovarian carcinoma MDAH2774 cells. Neither bilirubin, biliverdin nor carbon monoxide, direct products of HO-1 catalysed heme degradation, was responsible for cytoprotection. Importantly, desferrioxamine, a potent iron chelator significantly potentiated cytotoxic effects of PDT. Altogether our results indicate that HO-1 is involved in an important protective mechanism against PDT-mediated phototoxicity and administration of HO-1 inhibitors might be an effective way to potentiate antitumor effectiveness of PDT.

Animals↗
PubMed2005

Physics-based protein-structure prediction using a hierarchical protocol based on the UNRES force field: assessment in two blind tests.

Recent improvements in the protein-structure prediction method developed in our laboratory, based on the thermodynamic hypothesis, are described. The conformational space is searched extensively at the united-residue level by using our physics-based UNRES energy function and the conformational space annealing method of global optimization. The lowest-energy coarse-grained structures are then converted to an all-atom representation and energy-minimized with the ECEPP/3 force field. The procedure was assessed in two recent blind tests of protein-structure prediction. During the first blind test, we predicted large fragments of alpha and alpha+beta proteins [60-70 residues with C(alpha) rms deviation (rmsd) <6 A]. However, for alpha+beta proteins, significant topological errors occurred despite low rmsd values. In the second exercise, we predicted whole structures of five proteins (two alpha and three alpha+beta, with sizes of 53-235 residues) with remarkably good accuracy. In particular, for the genomic target TM0487 (a 102-residue alpha+beta protein from Thermotoga maritima), we predicted the complete, topologically correct structure with 7.3-A C(alpha) rmsd. So far this protein is the largest alpha+beta protein predicted based solely on the amino acid sequence and a physics-based potential-energy function and search procedure. For target T0198, a phosphate transport system regulator PhoU from T. maritima (a 235-residue mainly alpha-helical protein), we predicted the topology of the whole six-helix bundle correctly within 8 A rmsd, except the 32 C-terminal residues, most of which form a beta-hairpin. These and other examples described in this work demonstrate significant progress in physics-based protein-structure prediction.

Amino Acid Sequence↗
PubMed2005

[Lymph kinetics with technetium-99m labeled radiopharmaceuticals. Animal studies].

UNLABELLED: Aim of this study was to characterize suitable technetium-99m labeled tracers for lymphoscintigraphy by comparative animal tests. ANIMALS, METHODS: To evaluate the influence of the particle size and the organ tracer-uptake on lymphtransport animal experiments were performed on six different agents (including one control group). Activity distributions were examined in Sprague-Dawley-rats by lymphoscintigraphy; the maximum uptake (count-rate) of the whole body and in lymph nodes were analyzed by regions-of-interest-technique, respectively. Additionally, for characterization of lymphatic and extralymphatic traceruptake an intra-individual relative count-rate ratio of the liver, lung, kidneys, and spleen has been calculated following organ extraction. RESULTS: Organ specific differences of distribution were clearly demonstrated. Our results indicate that the kinetics of lymphoscintigraphic (99m)Tc-bound agents substantially depends on particle size. Reliable transport from the interstitium to initial lymph vessels and lymph node uptake suggested for tracers suited for lymphoscintigraphy a median size of about <100 nm. CONCLUSION: Our data could improve standardization of diagnostic methods and lead to an objective consideration of therapeutic procedures.

Animals↗
PubMed2001

Antitumor activity of tributyrin in murine melanoma model.

Butyric acid has been known to inhibit growth and to induce differentiation of a variety of tumor cells. Butyrate-treated tumor cells have also been observed to undergo apoptosis. Although butyrate compounds have demonstrated antitumor activity in murine tumor models and have already been admitted to clinical trials in tumor patients, the exact mechanism of their antitumor effects has not been elucidated. The results of our study showed antitumor activity of tributyrin, a butyric acid prodrug, in murine melanoma model and are strongly suggestive that antiangiogenic effects could participate in antitumor effects of butyrate compounds in vivo.

Animals↗
PubMed2001

Synthesis of tetrapeptide p-nitrophenylanilides containing dehydroalanine and dehydrophenylalanine and their influence on cathepsin C activity.

Three dehydrotetrapeptides of rationally varying structure were prepared and tested as affectors of cathepsin C. These compounds appeared to be substrates of the enzyme, being equipotent with their classical counterparts. Thus, replacement of amino acid in a short peptide by corresponding dehydroamino acid does not prevent cathepsin C in recognizing dehydropeptide as its substrate.

Alanine↗
PubMed2000

[Cyclic vomiting with ketosis as a cause of acute kidney dysfunction: own clinical experience].

The aim of the study was to evaluate renal activity during cyclic vomiting with ketosis. The clinical material was obtained from 50 cases of children hospitalized in Department of Pediatrics Military Medical University within 1993-1999 what makes about 1% of all patients. The examined group consisted of 26 boys (52%) and 24 girls (48%). Three of the children were repeatedly hospitalized (3 to 8 times) because of acetonemic vomiting. The special attention during the laboratory studies was paid to evaluation of renal activity. Vomiting with ketosis were associated with temporary kidneys acute dysfunction in 46% of cases. In 98% of cases the parenteral hydration was necessary. Ketonemic vomiting with kidneys dysfunction was observed mainly with the children in pre-school age.

Acute Disease↗
PubMed2000

[Nephropathy in the course of inflammatory connective tissue diseases].

The aim of the study was to assess the frequency of renal complications and also evaluation of renal efficiency with regard to sex and age in children with inflammatory connective tissue diseases. The examination embraced 18 children out of 5657 hospitalised in 19991-1998 in Military University School of Medicine-Dpt of Pediatrics suffering from inflammatory connective tissue diseases, which constitutes 0.32%. They found the following number of isolated cases: 9 cases of juvenile chronic arthritis (JCA), 6 cases of rheumatic fever (RF), and 3 cases of systemic lupus erythematosus (SLE). There were 9 girls and 9 boys. The most frequent symptom of kidneys affection was erythrocyturia. Due to chronic course, reccurrence and the possibility of further complications, children with inflammatory connective tissue diseases, after discharging from hospital, should stay under the care of rheumatological outpatient clinic.

Arthritis, Juvenile↗
PubMed2000

[Nephropathy in the course of Schönlein-Henoch purpura].

The aim of the study was to assess the frequency of renal complications and also evaluation of renal efficiency with regard to sex and age in children with Schonlein-Henoch purpura. 31 children with Schonlein-Henoch disease out of 5004 hospitalised in 6 years time (1994-1999) in Mil. Medical University-Dpt of Pediatrics, underwent the examination, which is 0.62% of all patients. The group of analysed cases consisted of 19 girls (61.3%) and 12 boys (38.7%). 15 of them had changes in kidneys, which constitutes 48.4%. The average age of examined children was 9.1 years. In the most cases upper respiratory tract infections preceded symptoms of the Schonlein-Henoch purpura. The most often complications found in the course of the Schonlein-Henoch purpura were renal ones. The most numerous renal complications affected children between 7 and 9 years of age. Because of chronic and insidious course of the disease, children, after discharging from hospital should stay under specialistic medical care.

Adolescent↗
PubMed2000

[Advanced abdominal angina due to atherosclerosis with atypical celiac arteries].

It is generally accepted that the abdominal angina develops only when at least two of the three splanchnic vessels-mesenteric arteries and the celiac trunk exhibit a critical obstruction. That common opinion does not, however, take into account anatomical variants of arteries supplying the blood to the intestines. We present a case of a wasted, 40 year old male with a wide spread arteriosclerosis and postprandial pain. The ultrasound examination revealed total occlusion of the superior mesenteric artery (SMA). Celiac trunk (CT) and inferior mesenteric artery (IMA) were patent. The ultrasound indicated that only one splanchic vessel was obstructed; the systemic disorder, the neoplasm, as well as the malabsorption were ruled out. An arteriography of the abdominal aorta and of splanchnic arteries confirmed patency of CT and IMA, also lack of flow in the SMA. Atypical origin of the middle colic artery originating from the bed of CT was also shown. Lack of collaterals between IMA and SMA, typically conducting a sufficient blood flow, resulted in a fully symptomatic abdominal angina. Symptoms were relieved following surgical revascularization.

Abdominal Pain↗
PubMed1995

Thymidylate synthases from Hymenolepis diminuta and regenerating rat liver: purification, properties, and inhibition by substrate and cofactor analogues.

Comparative studies of thymidylate synthases, isolated from the tapeworm, Hymenolepis diminuta, and regenerating liver of its host, rat, aimed at a possibility of specific inhibition of the helminthic enzyme, are presented. While similar in structure (dimers with monomer molecular masses of 33.7 kDa and 34.9 kDa, respectively) and parameters describing interactions with substrates and products, the tapeworm and rat enzymes differed in the dependences of reaction velocity on temperature (Arrhenius plots biphasic and linear, respectively). The tapeworm, compared with the host, enzyme was less sensitive to the competitive slow-binding inhibition by 5-fluoro-dUMP and its 2-thio congener, but equally sensitive to inhibition by 4-thio-5-fluoro-dUMP, N4-hydroxy-dCMP and N4-hydroxy-5-fluoro-dCMP, the latter being more potent inhibitor of the parasite enzyme than 5-fluoro-dUMP. alpha-Anomer of 5-fluoro-dUMP behaved as a very weak competitive slow-binding inhibitor of both enzymes. Both enzymes differed markedly in sensitivity to inhibition by 10-propargyl-5,8-dideazafolate and its di- and triglutamates (pddPteGlu1-3), with pddPteGlu1 being stronger inhibitor of the mammalian enzyme, but pddPteGlu3 showing opposite specificity. Sulfonamidobenzoylglutamate analogue of pddPteGlu (pddPteSO2Glu) and 2-desamino-2-methyl derivative of this analogue (CH3pddPteSO2Glu) were weaker inhibitors of both enzymes than the parent compound. Substitution of the glutamyl residue in CH3pddPteSO2Glu with either norvaline or alanine increased inhibition potency, whereas similar substitutions with glycine, valine or phenylglycine were without a distinct effect with the host enzyme but weakened inhibition of the tapeworm enzyme.

Animals↗
PubMed1985

Null cell identification and characterization with OKT16: an anti-p40 monoclonal antibody.

A murine monoclonal antibody, OKT16, specific for human lymphocytes of T lineage, was isolated by standard immunization and hybridization techniques. The distribution of the antigen defined by OKT16 was similar to the antigen reactive with monoclonal antibodies 3A1 and WT1. This identity of antigen targets was confirmed in an enzyme-linked immunosorbent assay system and by sequential immunoprecipitation. Under reducing conditions, OKT16 reacted with an antigen of 40K daltons; however, under nonreducing conditions this antigen appeared as an 84K-dalton molecule, which suggests that the p40 antigen exists as a disulfide-linked dimer. By indirect immunofluorescence, OKT16 reacted with a greater fraction of nonrosetting, non-B (null) lymphocytes than with antibodies to other T cell-specific proteins. Two-color immunofluorescence demonstrated the coexpression of the T16 antigen and the C3bi receptor on most null cells. The T10 antigen (found on cortical thymocytes and activated peripheral T cells) was restricted to most T16-bearing null cells and expression of the Fc receptor for aggregated IgG (defined by monoclonal antibody 73.1) was restricted to a major subset of T16-bearing null cells. The T cell-specific markers defined by OKT8, OKT11, and OKT17, as well as the monocyte marker defined by OKM5, were expressed by smaller subsets of OKT16-reactive null cells. These studies support by phenotypic analysis the functional heterogeneity ascribed to null cells. The 40K-dalton T16 antigen has the most extensive null cell representation of all the T lineage markers described to date.

Antibodies, Monoclonal↗
PubMed1984

Distinct classes of human T-cell activation antigens.

The characterization of three groups of antigens expressed by activated human T lymphocytes and detected by monoclonal antibodies is reported. Antigens defined by OKT19, OKT21, and OKT22 do not appear on in vitro activated T cells until increases in DNA synthesis become apparent and are not detected on most Interleukin 2 (IL-2)-independent cell lines and normal peripheral blood lymphocytes, monocytes, and granulocytes. Cell surface molecules reactive with the monoclonal antibodies OKT23 and OKT24 are displayed prior to any notable increase in DNA synthesis and are present on IL-2 independent cell lines, irrespective of lineage. T23 and T24 do not appear on peripheral blood cells and their distribution more closely resembles that of the T9 antigen (the receptor for transferrin) than antigens of the other groups. The third group of antigens, T14 and T20, have been classified as "early" antigens relative to DNA synthesis. They are expressed by distinct populations of normal lymphoid cells as well as by some IL-2-independent cell lines. Display of each group of activation antigens on T lymphocytes can be induced by either phytohemagglutinin, purified protein derivative from tuberculin, or allogeneic non-T cells, is not restricted to the OKT4+ or OKT8+ subsets, and is predominant on cells exhibiting the light-scattering properties of blast cells. The relative lack of expression of these antigens among normal peripheral blood cells make them attractive candidates for identifying changes in the status of immune activation.

Antibodies, Monoclonal↗
PubMed1983

Patterns of antigenic expression on human monocytes as defined by monoclonal antibodies.

A series of seven monoclonal antibodies directed at determinants on human peripheral blood monocytes were produced and characterized. The antibodies were separated into three groups based on cell distribution and percentages of monocytes bearing antigen. Hybridoma antibodies, termed OKM1, OKM9, and OKM10, recognized antigen(s) expressed on the majority of adherent monocytes, null cells, and granulocytes. The second group, comprising OKM5 and OKM8, reacted with most adherent monocytes and platelets. OKM3 and OKM6, comprising a third group of antibodies, reacted with a subpopulation of adherent monocytes and platelets. OKM antibodies were not expressed on lymphocytes, thymocytes, and lymphoblastoid cells, with the exception of OKM3 which reacted with three B-cell lines. SDS gels of immunoprecipitates formed with OKM antibodies yielded the following tentative molecular weight results: OKM1 and OKM9 antigens appeared to be 160,000 (nonreduced) and 170,000 (reduced); OKM10 precipitated two polypeptides of 170,000 and 115,000 (reduced); OKM5 and OKM8 precipitated a single polypeptide of 88,000 (reduced, nonreduced); OKM6 antigen appeared to be 116,000 (nonreduced) and 130,000 (reduced).

Animals↗
PubMed1983

Classification of human lymphocytes and monocytes with the OK series of monoclonal antibodies.

Membrane antigens expressed by either peripheral blood B cells, monocytes, or activated T cells have been identified by monoclonal antisera. OKB1, OKB2, OKB4, and OKB7 react with all or most circulating Smlg+ cells and have differential effects on the generation of plaque forming cells in the reverse hemolytic plaque assay. Of the new monocyte antibodies, OKM5 displays more restricted specificity for monocytes than the previously described OKM1, whereas OKM3 and OKM6 define monocyte subsets. In addition, several new T-cell "activation" antigens have been identified that differ in their expression depending on the nature of the triggering stimulus. These reagents should be of diagnostic and perhaps therapeutic utility.

Animals↗
PubMedDate not supplied

Butyric acid enhances in vivo expression of hTNF-alpha in transduced melanoma cell line.

Butyric acid (NaBut) and its derivatives are well-known agents eliciting tumor cell differentiation and apoptosis. In experimental models, NaBut is also used to enhance the efficacy of viral vectors. With the use of B78 murine melanoma cells transduced with the retroviral vector containing human tumor necrosis factor alpha (hTNF-alpha) gene, we investigated the ability of NaBut to increase the cytokine expression. We observed an increase in hTNF-alpha expression in vitro after incubation with NaBut. We also describe that the NaBut pro-drug tributyrin is able to increase hTNF-alpha expression in transduced B78 cells in a tumor vaccination model in mice. This observation strongly suggests a novel potential role for NaBut and its derivatives in tumor therapy. It could be used not only as a therapeutic directly acting on tumor cells but, in parallel, as a genetic vaccine "enhancer".

Animals↗