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Biomedical subjects

M Růzicka

Publications and source records attributed to M Růzicka.

At least 19 recordsLinked to original sources

[Solid pseudopapillary tumor of the pancreas: 5 case reports].

Solid pseudopapillary tumor of pancreas belongs to rare tumors of exocrine pancreas, which typically affects young women. In a retrospective study the authors reviewed their experience obtained with five cases of this tumor from 1994 until the present time. The group included four women (from 16 to 47 years, mean age 25 years) and one man (43 years old). Clinical symptoms were characterized by abdominal pain in three cases, two years lasting domed belly and an incidental finding in another case. The palpation examination of epigastrium revealed a palpable tumor, visible in sonographic examination and CT. All patients underwent surgical resection of the tumor. The tumor affected cauda of the pancreas (pancreatic tail) in four cases and head of the pancreas in one case. Histopathological examination established the diagnosis of solid pseudopapillary tumor of pancreas in four cases and solid pseudopapillary carcinoma in one case. A typical immunophenotype of tumorous cells was demonstrated and in four cases there was positivity of progesterone receptor. The progesterone and estrogen receptors were negative in the male patient. Solid pseudopapillary tumor of pancreas is the tumor of low malignancy with excellent prognosis. Correct diagnosis and surgical removal of the tumor results in curing up in most cases.

Adolescent↗

Mitochondrial uncoupling proteins--facts and fantasies.

Instead of a comprehensive review, we describe the basic undisputed facts and a modest contribution of our group to the fascinating area of the research on mitochondrial uncoupling proteins. After defining the terms uncoupling, leak, protein-mediated uncoupling, we discuss the assumption that due to their low abundance the novel mitochondrial uncoupling proteins (UCP2 to UCP5) can provide only a mild uncoupling, i.e. can decrease the proton motive force by several mV only. Contrary to this, the highly thermogenic role of UCP1 in brown adipose tissue is not given only by its high content (approximately 5 % of mitochondrial proteins) but also by the low ATP synthase content and high capacity respiratory chain. Fatty acid cycling mechanism as a plausible explanation for the protonophoretic function of all UCPs and some other mitochondrial carriers is described together with the experiments supporting it. The phylogenesis of all UCPs, estimated UCP2 content in several tissues, and details of UCP2 activation are described on the basis of our experiments. Functional activation of UCP2 is proposed to decrease reactive oxygen species (ROS) production. Moreover, reaction products of lipoperoxidation such as cleaved hydroperoxy-fatty acids and hydroxy-fatty acid can activate UCP2 and promote feedback down-regulation of mitochondrial ROS production.

Animals↗

Amplification and overexpression of HER-2/neu in invasive ductal carcinomas of the pancreas and pancreatic intraepithelial neoplasms and the relationship to the expression of p21(WAF1/CIP1).

Overexpression of HER-2/neu was described in pancreatic intraepithelial neoplasia (PanIN) and in invasive ductal adenocarcinoma of pancreas in a variable proportion of cases. The effects of HER-2/neu overexpression on mitogenic signalling and cell cycle progression were studied in breast luminal epithelial cells and mitogen activated protein kinase-dependent induction of p21(WAF1/CIP1) was found to be necessary for G1 phase progression. Overexpression of p21(WAF1/CIP1) was described as an early event in the development of PanIN by Biankin et al. (2001) and this finding was supported by our previous study that, moreover, did not confirm the possible role of activating K-ras mutations in the induction of p21(WAF1/CIP1) overexpression. Relationship between p21(WAF1/CIP1) expression and HER-2/neu status in PanIN lesions and ductal adenocarcinoma of the pancreas was investigated in our study. Expression levels of p21(WAF1/CIP1) and HER-2/neu were examined imunohistochemically and the amplification of HER-2/neu gene was evaluated by fluorescence in situ hybridisation in HER-2/neu overexpressing adenocarcinomas. Fourty nine pancreatic resection specimens from patients with invasive adenocarcinoma were included into the study. A large spectrum of PanIN lesions adjacent to the structures of infiltrating adenocarcinoma was also examined. The possible role of HER-2/neu in an induction of p21(WAF1/CIP1) overexpression was not confirmed and p21(WAF1/CIP1) overexpression seems to be HER-2/neu independent in pancreatic ductal adenocarcinoma according to our results. Increasing levels of HER-2/neu expression were demonstrated in pancreatic intraepithelial neoplasia and in 18.75% of pancreatic adenocarcinoma. The only 2 from 9 HER-2/neu overexpressing adenocarcinomas showed the amplification of HER-2/neu gene. Based on these results, the overexpression of HER-2/neu in pancreatic adenocarcinoma seems to be a result of increased transcription rather than gene amplification. Therefore HER-2/neu represents a good target for therapy of pancreatic adenocarcinoma only in isolated cases.

Adenocarcinoma↗

[Molecular diagnosis in pancreatic carcinoma].

Present diagnostic possibilities virtually do not make it possible to diagnose early stages of pancreatic cancer. Likewise, it is very difficult to differentiate between pancreatic cancer and chronic pancreatitis. The methods of visualization are insufficiently sensitive and the determination of certain genes could enrich our diagnostic opportunities. Considerable attention in this direction has been devoted to the determination and evaluation of the presence of oncogene K-ras. Our initial experience with the determination of K-ras in preparations from patients with pancreatic cancer or with chronic pancreatitis confirmed that K-ras in an oncomarker associated with adenocarcinoma of pancreas, whereas in patients with chronic pancreatitis it occurs in about 10% of the examined samples.

Adenocarcinoma↗

[Apoptosis and expression of bcl-2 protein in invasive ductal adenocarcinoma of the pancreas].

Apoptosis plays a central role in the development and/or progression of cancer. There are several methods for detection of apoptotic cells in tissue sections including light and electron microscopy, in situ nick end-labeling (ISEL), TdT-mediated dUTP nick-end labeling (TUNEL) and immunohistochemical detection of proteins associated with apoptosis. Apoptosis was assessed by the monoclonal antibody M30 CytoDEATH (M30), which is specific for neo-epitope in cytokeratin 18 that becomes available at an early caspase cleavage during apoptosis. Expression of bcl-2 protein was evaluated, because bcl-2 protein plays an important role in the regulation of apoptosis. Twenty-six invasive ductal adenocarcinomas of the pancreas were studied immunohistochemically with antibodies M30 and bcl-2. The mean apoptotic index (AI, the percentage of apoptotic cells of the total tumor cells number) was 2.75%. High AI (> 10%) was observed in 4 cases of the 26 pancreatic carcinomas (15%). Protein bcl-2 was expressed in 3 cases (11.5%). The AI did not correlate with the expression of protein bcl-2. In conclusion, the detection of neo-epitope in cytokeratin 18 by monoclonal antibody M30 can be used for quantification of apoptotic cells with immunohistochemical techniques in tissue sections. It is a new approach to evaluate apoptosis in pancreatic carcinomas. The low positivity of bcl-2 expression in pancreatic adenocarcinomas suggests that bcl-2 protein does not play a central role in pancreatic tumorigenesis and cancer progression.

Adult↗

[Chronic pancreatitis as a risk factor for pancreatic carcinoma].

Carcinoma of the pancreas is a very serious disease as regards early diagnosis, effective therapy and screening of the disease. Possible risk factors of development of carcinoma of the pancreas include chronic pancreatitis. In the submitted investigation the authors evaluated 213 patients under long-term (more than 5 years) dispensary care with the diagnosis of chronic pancreatitis. In these patients they proved unequivocally carcinoma of the pancreas on the background of chronic pancreatitis in 11 instances, incl. 71.8% where from the etiological aspect chronic alcoholic pancreatitis was involved. Practically all patients were smokers, incl. 8 who were regular smokers of more than 10 cigarettes per day for a number of years. Carcinoma of the pancreas is a serious disease, patients with long-term chronic pancreatitis are at risk (prevalence of carcinoma 5.1) and within the framework of dispensary care they must be systematically examined with regard to possible malignant growth on the background of chronic pancreatitis.

Adult↗

[Therapeutic results and changes in prognosis in patients with multiple myeloma in central and northern Moravia over the past 40 years].

OBJECTIVE: The objective of the investigation is evaluation of therapeutic results and the development of the prognosis of patients with multiple myeloma (MM) as a result of consecutive changes of therapeutic procedures in patients of central and northern Moravia in the course of the last 40 years. METHODS AND RESULTS: The analyzed group of 562 patients with MM was concentrated at the Ist and IIIrd Medical Clinic of the Faculty Hospital Olomouc in 1959 - 2000, median age 63 (28-91) male/female ratio 1.1: 1.0. From analysis of Kaplan-Meier survival curves and the results of statistical analysis (log rank test p = 0.0000) ensued that during the evaulated period a very substantial change of prognosis occurred with improvement of theraupeutic results and a significant prolongation of survival in general. The first " turning point" was the introduction of chemotheraphy with alkylating substances with Prednisone (1963-1975), leading as compared with the period of symptomatic treatment alone (1959-1063) to a significant prolongation of the media value of general survival (M) from 8 to 19 months (p = 0.0031) and 3-year survival from 4 to 23 % patients, whereby 10-year survival was only 0 % and 1 %. The second "turning point" was the period from 1976 - 1980 with introduction of systematic chemotherapy using conventional doses of polychemotherapeutic (CP) regimes with better opportunities of supporting treatment (M = 40 months, p = 0.0000; 3-year and 10-year survival 55% and 5.5% patients). The therapeutic results acheived during the subsequent 15 years were however an unsatisfactory advance. During the interval between 1976-1995 in a group of 295 patients divided into 5-year sub-periods remission was acheived (R = < 25 % of the baseline value of M-protein) in 10-24 % patients, an inadequate response (NR) = persistence in > 50 % M-protein) in 55-28 %, prolongation of the median of total survival in 232 of the accessble patients for 44 months and long-term survival of 5 - 10 years after establisment of the diagnosis increased from 25 to 36 % and from 5.5 to 16.5 % patients. The third "turning point" was 1996 characterized by the introduction of high-dosage chemotheraphy with transplantation of autologuos peripheral haematopoietic cells ("HD" therapy with ASCT) leading ina group of so far only 33, assessable patients under 65 years to acheived remission in 71 %, to decline of NR in 10 % only and 5 -year suvival so far in 91 % patients ( p = 0.0037). Improvement of therapeutic results and prognosis of the disease as compared with 1976 - 1995 occurred in the whole group of patients also in 1996 - 2000 (CP and "HD"-therapy with ASCT) characterized by remission in 36 %, NR IN 33 % and 5 -year survival in 57 % (p = 0.030). It was reveled that the application of "HD" theraphy with ASCT led in 1995-2000 to the acheivement of more favorable therapeutic results (R - 71 % NR - 10 %. 5-year survival after the interval which elapsed so far 91 %), as compared with 2 similar groups of subjects under 65 years meeting the criteria of "HD" theraphy with ASCT, but treated only by conventional polychemotheraphy (1991 - 1995 and 1996 - 2000: R - 24 and 32 %, NR - 42 and 23 %, 5-year survival 46 and 68 % of the patients). In the group of 148 patients from the period of 1991-2000 the patients had as regards remission (R) more favourable results as compared with patients with NR concerning the prognosis [M 63 vs.22 months, 5-year and 10-year survival 53 vs. 17 % and 17 vs. 0 % of patients (p = 0.0000)]. CONCLUSION: From the submitted analysis ensured that during the period form 1959 - 2000 in patients with mutiple myeloma in central and northern Moravia as a result of the application of modern methods of chemotheraphy and supporting treatment a significant improvements of results of conventional treatment occurred with a more than 5 fold prolongation of so far assessable median values of survival (8 - 44 months) and long-term 10-year survival of almost one sixth of the patients. The real asset of "HD" theraphy with transplantation of ASCT will be revealed by analyses made after a longer time interval.

Adult↗

[Surgical approaches to treatment of chronic pancreatitis].

In the treatment of pancreatitis in recent decades various surgical methods are used. Essentially we can divide them into resection and drainage methods. In the submitted paper the authors review possible surgical treatment of chronic pancreatitis and indications of optimal surgical methods in different forms of chronic pancreatitis. The application of these surgical procedures is demonstrated on a group of patients operated by the authors in 1985-2001. The authors discuss the problem of indication of patients for surgical treatment and selection of the optimal surgical methods for the treatment of chronic pancreatitis.

Humans↗

Natural and azido fatty acids inhibit phosphate transport and activate fatty acid anion uniport mediated by the mitochondrial phosphate carrier.

The electroneutral P(i) uptake via the phosphate carrier (PIC) in rat liver and heart mitochondria is inhibited by fatty acids (FAs), by 12-(4-azido-2-nitrophenylamino)dodecanoic acid (AzDA) and heptylbenzoic acid ( approximately 1 microm doses) and by lauric, palmitic, or 12-azidododecanoic acids ( approximately 0.1 mm doses). In turn, reconstituted E. coli-expressed yeast PIC mediated anionic FA uniport with a similar pattern leading to FA cycling and H(+) uniport. The kinetics of P(i)/P(i) exchange on recombinant PIC in the presence of AzDA better corresponded to a competitive inhibition mechanism. Methanephosphonate was identified as a new PIC substrate. Decanephosphonate, butanephosphonate, 4-nitrophenylphosphate, and other P(i) analogs were not translocated and did not inhibit P(i) transport. However, methylenediphosphonate and iminodi(methylenephosphonate) inhibited both electroneutral P(i) uptake and FA cycling via PIC. AzDA analog 16-(4-azido-2-nitrophenylamino)-[(3)H(4)]-hexadecanoic acid ((3)H-AzHA) bound upon photoactivation to several mitochondrial proteins, including the 30- and 34-kDa bands. The latter was ascribed to PIC due to its specific elution pattern on Blue Sepharose and Affi-Gel. (3)H-AzHA photolabeling of recombinant PIC was prevented by methanephosphonate and diphosphonates and after premodification with 4-azido-2-nitrophenylphosphate. Hence, the demonstrated PIC interaction with monovalent long-chain FA anions, but with divalent phosphonates of short chain only, indicates a pattern distinct from that valid for the mitochondrial uncoupling protein-1.

Affinity Labels↗

Existence of uncoupling protein-2 antigen in isolated mitochondria from various tissues.

Antibodies against Escherichia coli-expressed uncoupling protein-2 (UCP2) and uncoupling protein-3 (UCP3) were raised by operating the blotted proteins into the spleen of minipigs. The antisera reacted more intensively with the recombinant UCP2 and UCP3 than with uncoupling protein-1 (UCP1) isolated from brown adipose tissue. Moreover, anti-UCP2 and cross-reacting anti-UCP3 antibodies identified the presence of the UCP2/3 antigen in isolated mitochondria from rat heart, rat kidney, rat brain, rabbit epididymal white adipose tissue, hamster brown adipose tissue, and rabbit skeletal muscle. It has been concluded that UCP2 is expressed in these tissues (UCP3 in skeletal muscle); however their existence in mitochondria had not previously been demonstrated.

Animals↗

[Benign tumors of the pancreas].

The contemporary incidence of the tumours of the pancreas is approximately 3.5% in the Czech Republic. Benign tumours represent only about 2% of them. We have found 7 such patients (2.3%) in our population of 303 patients operated for pancreatic tumours. This paper summarizes our experience with the diagnostics and surgical treatment of these patients.

Aged↗

[Complications of esophageal stents used in benign esophageal stenoses].

Oesophageal stents are used in the treatment of stenosis of the oesophagus in the last 10 years. The application of the stent in benign stenosis should be exceptional because it is associated with high morbidity and mortality. Two cases with severe complications treated by operation are demonstrated. Types of stents for the treatment of the oesophageal stenosis are presented.

Aged↗

[Pathology of the pancreas. Analysis of 172 resection specimens].

New sophisticated surgical methods enabled interventions on pancreas which kept remaining without attention of gastrointestinal surgeons for a long time because of previously unsolvable reasons. Pancreatic resection specimens enter now the biopsy diagnostics the correct interpretation of which needs a perfect technology of processing. Biopsy under CT monitoring, fibroscopical techniques combined with contrast investigation, biochemical, cytological and bioptic analyses of samples brought new diagnostic aspects into pancreatic disorders. The authors present a classification analysis based on their group of 172 resection specimens from 165 patients: tumor lesions are represented by 52 specimens, inflammatory lesions by 112 specimens, 8 cases are of another nature or are lacking in a clear diagnostic classification. Bioptic investigation can settle the diagnosis of very rare nosological entities which were distinguished before only in necroptic material (adult nesidioblastosis, Schwachman-Diamond syndrome associated with ductal carcinoma of the head of pancreas, and others).

Biopsy↗

[Gangliocytic paraganglioma of the duodenum].

Gangliocytic Paraganglioma of the duodenum is rare neuroendocrine tumor. This type of the tumor can cause bleeding into the gastrointestinal tract and epigastric pain in this region. It can be difficult to differentiate this tumor from the primary tumor of the head of the pancreas growing secondary to the duodenum. The authors describe one such misdiagnosed case treated finally successfully by hemipancreatodecodenectomy.

Diagnosis, Differential↗

Photoaffinity labelling of the mitochondrial uncoupling protein by [3H]azido fatty acid affects the anion channel.

Brown adipose tissue (BAT) mitochondria were incubated with the azido derivative of fatty acid (hexadecanoic) containing four tritium atoms, [3H]AzHA, and among all mitochondrial proteins only a few proteins were photolabelled after irradiation with UV. It suggests the existence of specific fatty acid binding sites on mitochondrial proteins. It was also possible to label with [3H]AzHA the isolated uncoupling protein (UcP) of BAT mitochondria with a low stoichiometry--lower than one AzHA per dimeric UcP. These results together with the observed competition (i.e. prevention of photolabelling) of various UcP anionic substrates with [3H]AzHA and its dodecanoic acid analogue, suggest the existence of the specific fatty acid binding site on UcP identical with the anion channel or anion translocating site.

Adipose Tissue, Brown↗

[Retroperitoneoscopy--a new era].

Retroperitoneoscopy is a minimal invasive surgical technique enabling the diagnostics of the disease, as well as operative treatment of retroperitoneal organs. It is a very promising method especially for urologist, but of interest for general, vascular surgeon or gynecologist. The method is known since the end of sixties. Its routine introduction was enabled by technical advancement of laparoscopic surgery.

Endoscopy↗

[Retroperitoneoscopic lumbar sympathectomy].

The development of revascularization techniques of the distal lower extremity dramatically diminished the need of lumbar sympathectomy. Which is indicated when patient with rest pain or with a profound gangrene of toes (which does not exceed the line of metatarsal articulation) could not be treated by vascular reconstruction. Lumbar sympathectomy could be done surgically or chemically, the efficiency of which is about 50%. The second to the fourth lumbar sympathetic ganglion could be resected with minimal invasivity, retroperitoneoscopically. This approach to lumbar sympathectomy opens further possibilities for operating in retroperitoneal space. Retroperitoneoscopy is well tolerated by patients.

Endoscopy↗