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Biomedical subjects

J Procházka

Publications and source records attributed to J Procházka.

At least 19 recordsLinked to original sources

[Diagnostics and treatment of hepatocellular carcinoma. Recommendations of the Portal Hypertension Working Group of the Czech Hepatology Society and the J.E. Purkinje Czech Medical Society ].

Hepatocellular carcionma (HCC) is almost exclusively associated with liver cirrhosis as a significant HCC risk marker in advanced countries. Applicable therapy depends on early diagnosis, and risk patients should be screened for the presence of HCC on a regular basis. Liver ultrasound and determination of alpha-fetoprotein serum levels (AFP) are the screening methods used. Spiral CT is the most often used method for HCC staging. Non-invasive methods may under certain circumstances replace aimed biopsy. There are 3 basic curative therapies for the early stage of HCC: liver transplantation, surgical resection and different methods of local destruction of tumour (i.e., ethanolisation, thermoablation, etc.). Patients at medium stage of HCC may profit from chemoembolisation. Current available systemic chemotherapy is ineffective. Patients with advanced HCC are treated symptomatically. Patient survival prognosis after the application of one of the above treatment methods may be similar with that for HCC free cirrhosis patients, however, prognosis for advanced HCC patients is bad, with survival period from one to nine months.

Carcinoma, Hepatocellular↗

[C-reactive protein in diagnosis of complications in renal insufficiency and failure].

C-reactive protein (CRP) is one of the positive proteins in an acute phase. It is produced in hepatocytes in response to cytokines activity, especially to IL-6. Its increase is the second biggest after significant bacterial and cardiovascular insults. It reaches its peak between 24 and 48 hours. CRP monitoring makes possible monitoring of the intensity of the pathologic process and to control efficiency of treatment measures according to fluctuation of its level. According to its serum values it can reflect a place of inflammation, e.g. in upper or lower airways, urinary tract etc. It helps to distinguish between bacterial and viral inflammations and to identify size of vascular lesions such as acute myocardial infarction, cerebral infarction, decompensation of atherosclerosis. Because of its easy detection and quick elevation CRP has not only a diagnostic importance but also a prognostic one and is a predictor of a risk of atherosclerosis. Although long lasting renal insufficiency (LLRI), renal failure (RF) and regular dialysis treatment (RDT) are indicated to elevate CRP level, authors present proves that adequately treated patient compensated with an adequate dialysis treatment has normal CRP values for a long time in spite of long lasting comorbidities including atherosclerosis. There has been done a long term monitoring of 10 patients with LLRI and 22 patients with RDT. Their CRP was monitored via a turbidimetric method using sets K-Assay made by company Kamya Bio Comp. Elevated CRP in the samples reflects an acute insult such as infection, cardiovascular disease, diabetes decompensation and last but not least quality of a dialysis treatment.

Adult↗

[Ambulatory monitoring of blood pressure in regular dialysis therapy].

Ambulatory monitoring of the blood pressure (AMBP) makes it possible to diagnose in hypertensive patients the so-called dipper phenomenon, i.e. a drop of the BP during the night provided that the patient is asleep. The absence of this phenomenon implies as a rule serious damage of the cardiovascular apparatus, brain or kidneys. By means of an apparatus ABP monitoring type 90207 of Space Labs. Inc. a group of 16 patients in regular dialysis treatment (RDT) was examined and the blood pressures were evaluated before and after dialysis. Patients with the dipper profile reacted more adequately during dialysis i.e. by a drop of the blood pressure due to the loss of excessive fluid which they retained during the interdialysis period, as compared with the group with a non-dipper profile which may be exposed to a greater risk of cardiovascular complications. The authors conclude that detection of the absence of the non-dipper phenomenon can reveal risk patients. AMBP can explain so-called paradoxical hypertension at the end of haemodialysis despite major removal of fluids by ultrafiltration, and that moxonidine participates in a significant way in the elimination of the non-dipper phenomenon.

Blood Pressure Monitoring, Ambulatory↗

Arteriovenous malformations of the orofacial area.

Vascular lesions are pathological residues of the embryonic vascular system and can be divided into two main groups. The first group comprises haemangiomas, which are typical of childhood and involute spontaneously. The second group is formed by lesions without active proliferation, which include, among others, arteriovenous malformations that are congenital and grow proportionately with the subject. The authors present two cases of arteriovenous malformations of the orofacial area and discuss possibilities for modern diagnosis and treatment. Precise diagnosis and effective treatment of vascular lesions should be ensured by a diagnostic and therapeutic team of specialists from several disciplines (maxillofacial, ENT, plastic and general surgeon, paediatrician, haematologist, anaesthesiologist and possibly a neurosurgeon), headed by an intervention radiologist.

Arteriovenous Malformations↗

[Hemodynamic changes after sclerotherapy of esophageal varices in children].

The authors present an account on favourable late results of sclerotization of oesophageal varices in children. After sclerotization not only an immediate effect can be observed such as arrest of haemorrhage but also long-term favourable effects are found in the venous circulation of the splanchnic area.

Child↗

Regulation of cathepsin B activity by cysteine and related thiols.

We studied the mode of regulation of the activity of mature cathepsin B (CB) by L-cysteine and some related thiols. The activity of CB with Z-Arg-Arg-NHMec as substrate was gradually inhibited over a range of increasing concentration of Cys, Cys methyl ester (CysOMe), Cys ethyl ester (CysOEt), N-acetyl-Cys (N-AcCys) and 3-mercaptopropionic acid. However, the inhibition of CB peaked at a definite value of [Cys], [CysOMe], [CysOEt] and [N-AcCys] and was gradually reversed over a range of higher concentrations of Cys and its esters. The maximum inhibitory concentrations of Cys, CysOME, CysOEt and N-AcCys showed a positive relationship to the pKa(RSH) values of the thiols and those of CysOEt and Cys decreased with increasing pH. The capability of the thiols to overcome their own inhibitory effect on CB was dependent on the concentration of their thiolate anion (RS-). However, the preincubation-dilution experiments showed that Cys and N-AcCys did not interact with active CB via a covalent mode. The inhibition of CB by N-AcCys was competitive and could be reversed by CysOMe. This activity-recovering effect of CysOMe was concentration-dependent and obeyed the Michaelis-Menten saturation kinetics over a profound increase of [RS-]. CB reacting in an environment of concurrently decreasing [RS-] and increasing [RSH], which was achieved by means of carboxylesterase-catalyzed deesterification of CysOEt to Cys, was progressively inhibited. Cys and N-AcCys also inhibited the fragmentation of histone H4 by CB and their concentration-dependent inhibitory profiles were qualitatively similar to those observed with Z-Arg-Arg-NHMec. Taken together, the results indicate that the RSH form of Cys and related thiols inhibits the activity of CB while the RS- form of these thiols counteracts or reverses the inhibitory action of the RSH form. This previously unrecognized thiol-thiolate anion regulation mechanism might be involved in a dynamic regulation of CB activity in endosomes and lysosomes and at the sites of lysosome-driven pericellular proteolysis.

Cathepsin B↗

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↗

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↗

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↗

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↗

[Dissecting aortic aneurysm combined with hepatorenal syndrome].

The authors present a case of a dissecting aneurysm of the aorta type A which affected also the insertions of visceral and renal arteries, and in addition to renal ischaemia and impaired renal function caused also ischaemia of the liver parenchyma with a rise of transaminases and bilirubin. This led to temporary hospitalization at the infectious department where the patient was referred to rule out hepatitis. In the discussion the authors draw attention to the pathogenesis, differential diagnosis and contemporary therapeutic methods of the disease.

Aged↗

[Extrapulmonary tuberculosis with involvement of the reticuloendothelial system and secondary lupus vulgaris].

The authors describe a case of extrapulmonary tuberculosis with affection of the reticuloendothelial system in a 59-year-old female patient. After successful treatment the findings in the spleen, bone marrow and the laboratory results had normal levels. The authors draw attention to the diagnostic difficulties. They were able to confirm the diagnosis only by histological examination of biopsy from the pelvic bone. An interesting finding was eruption of lupus vulgaris on the legs in the course of treatment. The authors discuss some aspects of the disease and its differential diagnosis.

Bone Marrow Diseases↗

Early postnatal development of contractile performance and responsiveness to Ca2+, verapamil and ryanodine in the isolated rat heart.

Contractile performance of the isolated perfused rat heart and its inotropic response to Ca2+, verapamil and ryanodine was studied in 1-, 2-, 4-, 7- and 12-day-old animals. Values of the developed force revealed two different phases: a slow decrease from day 1 to day 4 followed by a steep increase up to day 12. A similar biphasic time course was observed in the magnitude of the inotropic effect of Ca2+ (0.6-10.0 mmol.l-1): decrease from day 1 to day 4 followed by an increase up to day 7. The sensitivity to Ca2+ was, however, not changed. An analogous biphasic response was also observed during perfusion with the calcium antagonist verapamil (10(-9) to 3.3 x 10(-7) mol.l-1): the sensitivity to negative inotropic effect rose from day 1 to day 4 and then decreased at day 7 (values of IC50 were 170 +/- 61, 17 +/- 6 and 171 +/- 60 10(-9) mol.l-1 S.E.M. on day 1, 4 and 7, respectively). The contractile response to the inhibitor of calcium release from sarcoplasmic reticulum (SR)--ryanodine (10(-6) mol.l-1)--was surprisingly high already in 1-day-old animals (inhibition of contraction by more than 50%) indicating the presence of functionally active SR in the rat heart just after birth. Our data clearly shows that the early development of contractile function and inotropic responsiveness of the rat heart is not linear and changes dramatically during the first week of life.

Aging↗

[Lipostat in the treatment of hyperlipoproteinemia].

Within the framework of clinical tests of LIPOSTAT (pravastatin tablets 20 mg Bristol Meyers-Squibb Co.) this hypolipidaemic preparation was administered to 28 patients with different types of hyperlipoproteinaemias, mainly of type IIa. Administration for a period of four weeks--20 mg in the evening--had a significant effect on several basic indicators of the lipid metabolism. The total plasma cholesterol level declined by 20%, the apolipoprotein B level by 11%, the HDL cholesterol level rose by 38% and the triacylglycerol level declined by 18%. During administration the serum levels of aminotransferases, creatine kinase and alkaline phosphatase did not increase. No adverse side-effects were observed which called for discontinuation of treatment. Pravastatin is according to the authors' experience and the results of others an effective hypolipidaemic agent, suitable for the majority of patients with hyperlipoproteinaemias, in particular those with elevated plasma cholesterol levels.

Adult↗

[Cystic lymphangioma of the retroperitoneum].

The authors present the case-history of a patient with a cystic retroperitoneal lymphangioma. Its diagnosis was established only by histological examination of the resected tissue. The authors draw attention to the symptomatology, diagnosis, therapy and discuss contemporary views regarding the cause of this disease.

Humans↗

Thyroid control of contractile function and calcium handling in neonatal rat heart.

Newborn rats were rendered hyperthyroid (daily subcutaneous injections of L-triiodothyronine, 10 micrograms 100 g-1 body weight) or hypothyroid (0.05% 6-n-propyl-2-thiouracil in drinking water to nursing mothers) during the first 3 weeks of postnatal life. Compared with the euthyroid group, hyperthyroidism resulted in: (1) cardiac enlargement with right ventricular preponderance, (2) increased cardiac contractile function, (3) increased Ca2+ uptake by the sarcoplasmic reticulum (SR), (4) decreased sensitivity to the negative inotropic effect of verapamil and (5) greater inhibition of contractile function by ryanodine. Hypothyroidism generally resulted in opposite changes. The data suggest that the development of the heart and its contractile function during early postnatal life depends on the plasma level of thyroid hormones. In particular, the relative contribution of the SR and sarcolemmal Ca2+ transport to the control of cardiac contractility seems to be markedly affected by altered thyroid states. The postnatal maturation of the SR function is accelerated in hyperthyroidism but retarded in hypothyroidism. Consequently, hyperthyroid hearts appear to be less dependent and hypothyroid ones more dependent on trans-sarcolemmal Ca2+ fluxes when compared with age-matched euthyroid animals.

Animals↗