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Biomedical subjects

J Cermák

Publications and source records attributed to J Cermák.

At least 19 recordsLinked to original sources
PubMed1999

Double minute chromosomes in a patient with myelodysplastic syndrome transforming into acute myeloid leukemia.

Presence of double minute chromosomes (dmin) is rare in bone marrow cells in patients with preleukemia and leukemia. We describe a case of myelodysplastic syndrome-refractory anemia with excess of blasts (MDS-RAEB) associated with two unrelated pathological chromosomal clones that developed during the progression of the disease. The patient was followed cytogenetically for a period of 4 years. At the time of transition into RAEB-T and later to acute myeloid leukemia (AML), dmin were associated with resistance to chemotherapy. Fluorescence in situ hybridization study proved that the dmin in this case were c-MYC amplicons. At the terminal stage of the disease, dmins were present in all 50 analyzed cells.

Blast Crisis↗
PubMed1999

[A preventive ostomy in low rectal resections].

Dehiscence of the anastomosis after low resection of the rectum is a serious complication with the possible development of sepsis and multiorgan failure. This complication is reported in 10-20% of operations. The incidence of dehiscences can be reduced when known principles of preoperative care are respected but in particular by correct surgical technique. The serious character of this surgical complication can be reduced by a primary derivative stomy. Based on their experience the authors recommend to implement a preventive ileostomy in low resections of the rectum which can be closed already two weeks after the primary operation.

Aged↗
PubMed1998

[Interferon alpha--the drug of choice for patients with chronic myeloid leukemia].

BACKGROUND: The conventional, or standard, treatment of chronic myeloid leukaemia (CML) with hydroxyurea and busulfan has no marked influence on its course or duration. Interferon (IFN) alpha administration has, on the other hand, been shown to induce not only a haematological but also cytogenetic response, i.e. partial or complete bone marrow repopulation by Ph-negative cells. This has triggered studies comparing IFN and conventional chemotherapy. The present work had the purpose to gain experience with IFN alpha treatment and compare the results with hydroxyurea and busulfan treatment, in the chronic phase of CML. METHODS AND RESULTS: Therapeutic results obtained in 30 patients given IFN alpha and 30 others given conventional chemotherapy were evaluated retrospectively. In spite of the short time of IFN administration (4-27 months), significantly more complete haematological responses (83%) were observed in this than the conventional chemotherapy group (57%). Cytogenetic responses were achieved in 36%, complete cytogenetic remission in 20% of IFN-treated patients. Conventional chemotherapy produced no cytogenetic effect. CONCLUSION: The results obtained confirm the value and efficacy of IFN-alpha treatment in CML patients, especially if it is started early and the dose is effective. Regular cytogenetic monitoring is necessary. Longer follow-up of the patients will be necessary for evaluation of the IFN effect on the length of their survival.

Adult↗
PubMed1998

Cyclosporin A therapy in hypoplastic MDS patients and certain refractory anaemias without hypoplastic bone marrow.

We report 17 cytopenic patients with myelodysplastic syndrome (MDS) of refractory anaemia (RA) subtype with hyper-, normo- or hypo-cellular bone marrow (BM), who were treated with cyclosporin A (CyA). Substantial haematological response was observed in 14 patients (82%): their anaemia improved and all transfusion-dependent patients achieved transfusion independence. Complete trilineage recovery was observed in four patients (23%). The CyA therapy has not yet failed in any of the 14 successfully treated patients during follow-up times ranging from 5 to 30 months. CyA was well tolerated in 14 patients; serious side-effects required termination of the therapy in three patients in whom the blood count rapidly deteriorated to former levels upon cessation of therapy. Two patients benefited from a combination therapy of CyA and erythropoietin. Six patients experienced various autoimmune phenomena. CyA could thus offer an alternative treatment for certain MDS patients with RA regardless of hyper-, normo- or hypo-cellularity of bone marrow (BM). The mechanism of the beneficial effect of CyA is discussed and remains the subject of an ongoing study.

Adult↗
PubMed1998

P230 BCR/ABL protein may be associated with an acute leukaemia phenotype.

The BCR/ABL rearrangement, the molecular hallmark of chronic myelogenous leukaemia (CML), is rare in acute myeloid leukaemia (AML), being detected in approximately 1% of cases. In the vast majority of CML cases the breakpoint on chromosome 22 falls in the so-called major breakpoint cluster region of the BCR gene. Only a few cases of CML with breakpoint in the minor or in the micro bcr region have so far been reported. The micro breakpoint position has been associated mainly with a mild form of CML, defined as Philadelphia chromosome-positive chronic neutrophilic leukaemia (Ph-positive CNL). Using reverse transcription-polymerase chain reaction (RT-PCR) we report a patient with an acute myeloid leukaemia phenotype at diagnosis who showed a BCR/ABL rearrangement with a breakpoint located in the micro bcr region (e19a2 junction). Cytogenetic analysis showed a progression of the malignant clone, finally leading to cells with two Ph chromosomes, trisomy 8, isochromosome 17q and deletion of the long arms of chromosome 7. The findings of chromosomal changes point to a possibility of blast crisis of CML with a clinically silent chronic phase. Immunoprecipitation and auto-phosphorylation assay revealed the expression, by the patient's blast cells, of an abnormal P230 BCR/ABL protein, which showed for the first time that this protein was constitutively activated in primary cells from patients. This finding may contribute to the understanding of the role of the BCR/ABL rearrangements in determining different leukaemia phenotypes ranging from acute lymphoid and myeloid leukaemias to mild chronic neutrophilic leukaemias.

Acute Disease↗
PubMed1998

[Haplotypes of the beta-globulin locus in Czechs and Slovaks with beta-thalassemia and structurally variant hemoglobins].

In 29 Czech and Slovak families with the most frequent and newly identified beta-thalassaemic alleles and with some structural haemoglobin variants (Hb E, Hb Haná, Hb Santa Ana) haplotypes of the beta-globin locus of alleles with these mutations were identified. In most instances haplotypes I and V were involved which were found in 57% of the patients. The bond of the most common beta-thalassaemic mutation: IVS-I-1, IVS-I-110, CD 39 (C-T), IVS-II-745, IVS-I-6 with alleles with the same haplotypes as in the mediterranean region suggests a mediterranean origin of these mutations. In Hb Santa Ana a hitherto not described haplotype was identified (-(+)-(-)-(+3), indicating a de novo origin of the mutation. Also in newly identified beta-thalassaemic mutations in CD 7/8 (+G), in CD 38/39 (-C) and in HbE and Hb Haná de novo development is probable.

Czech Republic↗
PubMed1998

[Explorative thoracotomy in patients with bronchogenic carcinoma].

The authors analyse in a retrospective study a group of 31 patients with explorative thoracotomy, which was performed on account of inoperable bronchogenic carcinoma. The causes of inoperability were assessed and the period of survival after explorative thoracotomy was evaluated. From the total number of 496 patients indicated in 1985-1990 for surgery on account of bronchogenic carcinoma 465 pulmonary resections were made and 31 (6.25%) explorative thoracotomies. In all these patients the c TNM and p TNM classification was assessed. Disagreement in the evaluation of these parameters was found in particular in parameter T which was in agreement only in three instances. Conversely agreement was more frequent in parameter cN and pN (n = 18). The most frequent cause of inoperability was penetration of the tumour into the mediastinum (n = 25). Death within 30 days after surgery was not recorded in the group, three patients of 31 survived 5 years after exploration. Explorative thoracotomy did not exert a negative effect on the period of survival which corresponded to the given stage of the disease. Due to improving preoperative examination methods the number of explorative thoracotomies will probably decline in future, but at present it cannot be completely eliminated.

Adult↗
PubMed1998

[The significance of cytokines in the early diagnosis of postoperative intraabdominal sepsis].

The objective of the investigation was to evaluate the possible use of selected cytokines and cytokine receptors in the early diagnosis of postoperative intraabdominal sepsis. The investigation was focused on the dynamics of plasma levels of tumour necrotizing factor-alfa (TNFalfa), interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-10, soluble receptors IL-2 and IL-6 (sIL-2R and sIL-6R) and the receptor antagonist IL-1 (IL-1ra). The investigated parameters were tested on model operations (resection of large bowel and resection of pancreas). These two groups were compared with values recorded in patients with sepsis and with healthy subjects. Based on the assembled results the authors recommend to use for postoperative investigations the first 48 hours and to follow up the following parameters: IL-6, IL-ra or sIL-2R. During the first 48 hours these indicators differentiate sufficiently specifically incipient sepsis from an uncomplicated postoperative condition. During the subsequent period, i.e. more than 48 hours after surgery, it is useful to include in the examination pattern also some acute stage proteins (C reactive protein, alfa1-antitrypsin and haptalobin) which differentiate sepsis between the 3rd and 5th day after surgery.

Abdomen↗
PubMed1998

Cysteine proteases and cysteine protease inhibitors in non-small cell lung cancer.

In this study we investigated the levels of two lysosomal cysteine protease proteins cathepsin B (CB) and cathepsin L (CL) and the levels of three cysteine protease inhibitor proteins stefin A (SFA), stefin B (SFB) and cystatin C (CNC) in squamous-cell lung carcinoma (SQCLC) and matched lung parenchyma specimens and examined the inhibition of CB and cathepsin C (CC) activities by endogenous inhibitors in extracts from SQCLC, lung adenocarcinoma (LAC) and lung parenchyma specimens. We found that Stage I SQCLCs contained significantly increased levels of CB protein, CB activity and SFA protein as compared to matched lungs. Neither the levels of CL protein nor the levels of SFB protein nor the levels of CNC protein in Stage I SQCLCs and the lungs were significantly different, but the levels of CB and CL proteins as well as the levels of SFA and SFB proteins showed significant positive correlation in SQCLCs. In SQCLCs as well as in the lungs the level of SFB protein was significantly higher than the level of SFA protein or the level of CNC protein. In the lungs the levels of SFA protein and CNC protein revealed a weak negative correlation trend. In extracts from SQCLCs the level of SFA protein showed a weak negative correlation with the residual CB activity (i.e. the activity remaining after extract preincubation) whereas in extracts from the lungs the level of CNC protein displayed a weak negative correlation trend with the residual CB activity and with the residual CC activity. We observed that SQCLCs and LACs contained not only a significantly increased activity of CB but also a significantly higher inhibitory potential against the activity of endogenous CB as compared to matched lungs. Leupeptin, a small inhibitor of CB, was capable to protect CB in lung carcinoma and lung parenchyma extracts from preincubation-induced inhibition, revealing an active-site directed and competitive nature of CB inhibition by endogenous cystatins. Ultrafiltration passaged protein preparations of nominal Mr < or = 30,000 obtained from extracts of SQCLCs inhibited significantly higher quantities of activity of purified bovine spleen CC than did such protein preparations from matched lungs. Reaction courses of purified bovine spleen CC that had been preincubated with such protein preparations resembled those of endogenous CC from SQCLC and lung extracts showing a slow steady-state approach. These observations and the relaxation kinetics of CC from SQCLC and lung extracts suggest that CC in the extracts may be complexed with some cystatins. In conclusion, our results indicate that quantitatively different combinations of cystatins are the major constituents of the inhibitory potential against CB and CC in SQCLCs and the lungs.

Adenocarcinoma↗
PubMed1997

[Mixed myelodysplastic and myeloproliferative syndromes].

BACKGROUND: An injury to the hemopoietic stem cell may lead to the aplasia of hemopoiesis, myelodysplasia and to an unregulated myeloproliferation. There is not a strict demarcation of them, so that mixed syndromes can develop as are hypoplastic syndromes on one side and mixed myelodysplastic and myeloproliferative syndromes (MDS-MPS) on the other side. METHODS AND RESULTS: Among our 616 pts with MDS we looked for those cases, who had beside myelodysplasia signs of myeloproliferation with increased number of blood cells. They were examined in detail including bone-marrow histology, bone marrow cultivation, cytogenetics and bcr-abl gen. Signs of MDS-MPS were found in 22 patients at the first contact with the patient (13 patients had thrombocytemia and 9 patients had leukocytosis). Further 7 patients were diagnosed as MDS, proliferative syndrome developed after several months (MDS-MPS in evolution). The level of thrombocytemia was relatively stable, the number of leukocytes was progressive. All subtypes of MDS were found. All subjects had variable degree of anemia. Ring-sideroblasts and myelofibrosis were frequent finding in MDS-MPS. Men prevailed in patients with leukocytosis. Cytogenetic and cultivation findings were similar to MDS cases, deletion of long arm of chromosome 20 was present in 3 patients. Five patients transformed to acute myeloid leukemia. CONCLUSIONS: Sings of myelodysplasia and myeloproliferation were found in 4% of our MDS patients, designated as mixed myelodysplastic and myeloproliferative syndrome (MDS-MPS). In this syndrome beside evident signs of myelodysplasia thrombocythemia or leukocytosis with the release of bone marrow precursors are present. In only one case polycythemia was encountered.

Adult↗
PubMed1997

Solid-phase extraction in malondialdehyde analysis.

Malondialdehyde (MDA) has been widely used as an index of lipoperoxidation in biological and medical sciences as well as in the food industry. A solid-phase extraction (SPE) of the condensation product of the MDA with 2-thiobarbituric acid (TBA) was developed using LiChrolut C18ec, 200 mg (Merck, Darmstadt, Germany), as a SPE cartridge and methanol as an eluent for sample pretreatment before HPLC analysis. The samples of blood plasma, platelet concentrates, or erythrocyte membranes (ghosts) were deproteinized by acetonitrile in the presence of sodium hydroxide prior to the reaction with TBA. The reaction mixture was processed using SPE. The SPE extracts (800 microL of methanol) were put to dryness and after dissolution with 100 microliters of mobile phase, 50 microliters was analyzed by RP-HPLC with fluorescence detection (excitation at 514 nm, emission at 556 nm). The mean MDA concentration in plasmas of 32 healthy donors was 0.37 +/- 0.25 mumol/L and the mean MDA concentration in normal ghosts was 8.3 +/- 4.1 pmol/microgram of protein content. In the case of a patient with a severe form of beta-thalassemia, the concentration of plasma MDA was raised to 1.22 mumol/L and the amount of MDA in erythrocytal ghosts was raised to 21.05 pmol/microgram of protein content. MDA concentration in platelet concentrates (six bags) in the first day of storage was 0.46 +/- 0.18 mumol/L and in the fifth day of storage was 0.55 +/- 0.44 mumol/L.

Blood Platelets↗
PubMed1997

[Results of resection of a stage IIIA/N2 non-small cell bronchogenic carcinoma].

The authors analysed a group of 80 patients who were operated in 1985-1990 on account of non-small cell carcinoma of the lungs in stage IIIA with affection of the ipsilateral mediastinal nodes. The patients were not treated by neoadjuvant chemotherapy and systematic dissection of the mediastinal nodes was not performed. The results of five-year survival in the group of patients with affection of the mediastinal nodes (N2) were compared with those in the group of patients without affection of the mediastinal and hilar nodes (NO). Patients with affected N2 nodes who survived five years were significantly fewer than patients with negative mediastinal and hilar nodes. The probability of five-year survival in N2 was 15.8%, in patients with NO 28.0%. From data in the literature it is known that neoadjuvant chemotherapy and subsequent complete resection of the lung with the tumour combined with dissection of the mediastinal nodes may improve long-term survival after surgery. The authors assume that introduction of the described methods in their department will improve postoperative results.

Adult↗
PubMed1997

[Relation between types of erythrocyte membrane defects and the clinical picture in hereditary spherocytosis].

From total number of 130 patients with hereditary spherocytosis from 75 families in 119 patients from 69 families a defect of membrane proteins was detected. In 23 families (33.3%) a spectrin defect was involved, in 32 families (46.3%) a combined defect of spectrin and ancyrine and in 14 families (20.3%) a defect of band 3 proteins. Investigation of the membrane defect and the clinical and laboratory picture revealed that the band 3 protein defect of spectrin and ancyrine. There are significant differences in the clinical picture of the two latter defects.

Adult↗
PubMed1997

Cathepsin B, thiols and cysteine protease inhibitors in squamous-cell lung cancer.

We investigated activities of the cysteine protease cathepsin B (CB; EC 3.4.22.1), the levels of reduced glutathione (GSH) and cysteine and the activity of gamma-glutamyltransferase (gamma-GT; EC 2.3.2.2) in squamous-cell lung carcinoma (SQCLC) and the lung parenchyma specimens from surgically treated patients. The basal CB activity, assayed in tissue extracts in the absence of exogenous activators, was significantly higher in SQCLC compared to the lung. The residual CB activity, remaining in tissue extracts after preincubation at 37 degrees C, was not any longer significantly different in SQCLC and the lungs. The inhibited CB activity, calculated as the difference between the basal and residual CB activities, was significantly higher in SQCLC compared to the lung. In the case of the cysteine protease cathepsin C (CC; EC 3.4.14.1), neither the basal nor the residual nor the inhibited CC activities in SQCLC and the lung were significantly different. Compared to CC, the powerfulness of endogenous cysteine protease inhibitors to inhibit CB was much higher in both SQCLC and the lung. The cysteine protease inhibitors from SQCLC and the lung which effectively inhibited CB could be related to the inhibitors with an apparent M(r) ranging from 10,000 to 30,000. Isoelectric focusing studies indicated significant differences in the progress of inhibition of the activity of CB isoforms in SQCLC and lung parenchyma extracts. The levels of both GSH and Cys were significantly higher in SQCLC compared to the lung and the level of GSH was significantly higher in Stage III tumors compared to Stage I tumors. The activity of gamma-GT was not significantly different in SQCLC and the lung but it was significantly higher in Stage I tumors compared to Stage III tumors and showed a significant negative correlation with GSH level in SQCLC. Dithiothreitol did not increase the basal activity of CB from SQCLC and the lung which indicates that reversibly oxidized forms of CB do not accumulate in the tumors and the lungs. The basal activity of CB from SQCLC and the lung was competitively inhibited by Cys. Moreover, increasing Cys concentrations had a modulatory effect on the basal activity of CB from SQCLC and the lung which was featured by Cys-induced inhibition of CB activity and by subsequent Cys-effected recovery of CB activity from its previous inhibition by Cys.

Adult↗
PubMed1996

Lysosomal dipeptidyl-peptidases I and II in human squamous cell lung carcinoma and lung parenchyma.

In the present work we studied the levels of activities of dipeptidyl-peptidase I (or cathepsin C, DPP-I) and dipeptidyl-peptidase II (DPP-II) and examined their isoelectric focusing profiles in matched pairs of human squamous cell lung carcinoma (SQCLC) and the lung from surgically treated patients (n = 33). The mean specific activities of DPP-I and DPP-II were higher in SQCLC (Stages I and II) than in the lung, but only the activity of DPP-II in Stage I SQCLC was significantly higher compared to the lung. The activities of both enzymes were higher in the tumor than in the lung in 10 of 20 Stage I SQCLC patients, but only in 3 of 13 Stage II SQCLC patients. The specific activities of DPP-I and DPP-II in the lungs showed a good correlation while the correlation of both enzyme activities in SQCLCs was poor. We observed only a small and mutually comparable activation of DPP-I in extracts from SQCLCs and from the lungs by dithiothreitol. The isoelectric focusing profile of several DPP-II forms in SQCLCs and the lungs was similar and the single major DPP-II isoform revealed in the tumors and lungs showed a pIapp of 5.3-5.2. The isoelectric focusing profile of DPP-I showed multiple enzyme forms in SQCLCs (pIapp 6.3-4.5) as well as in the lungs (pIapp 6.4-4.8). In SQCLCs, as well as in the lungs, the activities of the DPP-I forms with pIapp values < or = 5.6 were shifted by neuraminidase treatment to the site of the major DPP-I isoform with pIapp of about 6.0 and the zymograms then showed an another DPP-I with pIapp of 5.7, which was less discernible in the lung. In some patients, the DPP-I forms with pIapp values < or = 5.6 from SQCLC retained a greater percentage of activity distribution than did the DPP-I pIapp-counterparts from the lung.

Adult↗
PubMed1996

[Acute resection of the large intestine].

The authors evaluate the results of 32 acute resections of the large intestine on account of a malignant process or an inflammatory aetiology causing obstruction. They recommend to prefer this method to multi-stage operations even in patients of advanced age, if their general condition permits it.

Adult↗
PubMed1995

Multiple forms of cathepsin B in human lung cancer.

In this study we have examined, by means of isoelectric focusing (IEF) in native polyacrylamide gel and contact-print fluorescence zymography, whether human lung carcinomas and the lung parenchyma contain different pools of multiple charge forms of the cysteine proteinase cathepsin B. The isoelectric point (pI) patterns of cathepsin B from lung carcinoma and matched lung were similar, particularly with regard to 2 major intermediate acidic enzyme pI forms designated as I and II (pIapp of 5.10 and 4.93 in tumors, and 5.11 and 4.94 in lungs, respectively). The slightly acidic cathepsin B pI forms (pIapp 5.47-5.19) in squamous-cell lung carcinoma (SQCLC) were significantly more numerous than such enzyme pI forms in lungs. The numbers of the highly acidic cathepsin B pI forms (pIapp 4.82-4.33) were significantly higher in SQCLC and lung adenocarcinoma (ACL) than in matched lung. The activity distribution percentage in the set of highly acidic cathepsin B pI forms was significantly higher in SQCLC and ACL than in matched lung. We also observed that cathepsin B from SQCLC and matched lung was fully recoverable by IEF from inhibition by leupeptin. Using the cysteine-proteinase-specific inactivator E-64, we revealed by IEF that some cathepsin B isoforms (charge forms) from SQCLC were more resistant to inactivation by this compound than the corresponding enzyme isoforms from lungs. After IEF, the enzyme isoforms apparently lost their resistance to E-64. Our results indicate that the pool of multiple charge forms of cathepsin B in SQCLC and ACL is different from that in the lung, and also that there may be an increased level of loose complexes between cathepsin B and some proteins or polypeptides in SQCLC compared to the lung.

Adenocarcinoma↗