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Biomedical subjects

M Jirsa

Publications and source records attributed to M Jirsa.

At least 19 recordsLinked to original sources

[Fluorescence cystoscopy in the diagnostics and treatment of superficial urinary bladder tumors].

BACKGROUND: 5-aminolevulinic acid induced fluorescence cystoscopy can detect more tumour lesions comparing to standard cystoscopy. The goal of our study was to assess the influence of fluorescence cystoscopy used during transurethral resection on the recurrence rate and the length of tumor-free interval in stage Ta, Tl transitional cell carcinoma of the urinary bladder. METHODS AND RESULTS: In prospective randomized study 109 patients with primary or recurrent stage Ta Tl bladder transitional cell carcinoma treated with transurethral resection were enrolled. 17 patients with high grade tumors were evaluated separately. In group A the transurethral resection was performed with standard white light endoscopy, in group B with fluorescence cystoscopy. The patients were followed using standard cystoscopy and urinary cytology. Recurrence free interval was evaluated in whole groups and also for single and multiple and for primary and recurrent tumors separately. The median time to recurrence was 8.05 months in group A and was significantly shorter than 13.54 months in group B (p = 0.04, log-rank test). In separate analyses the median time to recurrence was significantly shorter using fluorescence cystoscopy in multiple (p = 0.004) and in recurrent (p = 0.02) tumors, but not in solitary and primary tumors. CONCLUSIONS: 5-aminolevulinic acid induced fluorescence cystoscopy used during transurethral resection reduces the early recurrence rate in stage Ta Tl bladder transitional cell carcinoma.

Aged↗

Effect of chloroquine wash-out period of photosensitizers in the skin and selected organs in rats.

In the last decade, photodynamic therapy has become an alternative method for the diagnosis and therapy of tumors. In human medicine hematoporphyrin derivatives, sulfonated hydrophilic meso-tetraphenylporphyrin (TPPS4) and an oligomer of hematoporphyrin (Photosan 3), are widely used. Chloroquine is used for the treatment of porphyria cutanea tarda for its power to release porphyrins from the liver tissue. The kinetics of two porphyrin photosensitizers TPPS4 and Photosan 3 in the skin and some organs as well as the effect of chloroquine on the porphyrin excretion and their accumulation in skin and organs of Wistar rats were studied. TPPS4 exhibited maximum fluorescence in skin 48 h after application with decreasing to basal level from the 8th to the 14th day. Maximum fluorescence was reached at 72 hours after Photosan 3 application and it decreased to basal level during 96 hours after application. TPPS4 caused significantly higher fluorescence compared to Photosan 3. Chloroquine after oral administration did not change the fluorescence of skin, but it significantly decreased the TPPS4 concentration in rat organs if chloroquine treatment started 3 days or 2 weeks after TPPS4 application. Chloroquine significantly decreased the serum TPPS4 concentration during the period of 28 days. Fluorescence of skin was significantly higher and lasted longer after application of TPPS4 compared to Photosan 3. Chloroquine after oral administration did not influence the fluorescence of the skin, but it significantly decreased the TPPS4 concentration in rat organs. This effect could be useful in photodynamic therapy for mobilizing exogenous porphyrins from tissues after parenteral photodynamic therapy.

Administration, Oral↗

Effect of acute hyperglycaemia on selected plasma and urinary cytokine antagonists in Type 1 diabetes mellitus.

AIMS/HYPOTHESIS: Several cytokines have been implicated in the pathogenesis of diabetic nephropathy. Their ability to generate a biological response in vivo is modulated by specific antagonists and soluble receptors. The aims of the study were firstly, to measure the interleukin 1 receptor antagonist (IL-1ra) and tumour necrosis factor alpha soluble receptors p55 (TNFsr1) and p75 (TNFsr2) in plasma and urine, and secondly to test their response to acutely induced hyperglycaemia in Type 1 diabetes mellitus (DM 1). METHODS: Plasma concentrations and urinary excretions of IL-1ra, TNFsr1 and TNFsr2 were measured in two 90-min periods of glycaemic clamp-induced normoglycaemia and hyperglycaemia (5 and 12 mmol/l; study 1) and during time-controlled normoglycaemia (5 and 5 mmol/l; study 2) in 20 Type 1 diabetic patients with normal albumin excretion and normal glomerular filtration rate, and in 11 weight-, age- and sex-matched healthy control subjects. RESULTS: The plasma concentrations of IL-1ra, TNFsr1 and TNFsr2 were comparable in Type 1 diabetic patients and control subjects, and no significant changes during study 1 and study 2 were found. Urinary IL-1ra excretion measured during normoglycaemia was higher in Type 1 diabetic patients compared to control subjects ( p<0.05). In diabetic patients, it decreased in study 1 compared to study 2 ( p<0.05), while it did not change in control subjects. The urinary excretions of TNFsr1 and TNFsr2 during normoglycaemia were comparable in diabetic patients and controls. In diabetic patients, hyperglycaemia decreased TNFsr1 excretion (study 1 vs study 2; p<0.01), while TNFsr1 excretion did not change in control subjects. Hyperglycaemia did not affect TNFsr2 excretion in diabetic patients, while it led to an increase in TNFsr2 excretion in control subjects (study 1 vs study 2; p<0.05). Despite comparable renal haemodynamics, diabetic patients had lower fractional excretion of sodium compared to control subjects ( p<0.01). No significant relationships between cytokine antagonists and renal functions have been found. CONCLUSION/INTERPRETATION: Type 1 diabetic patients with normal renal haemodynamics are associated with impaired regulation of renal IL-1ra, TNFsr1 and TNFsr2 production with a potential impact on local control of cytokine activity in the kidneys.

Adult↗

[Fluorescence cystoscopy using 5-aminolevulinic acid].

BACKGROUND: Fluorescence diagnosis has an increasing importance in different medical fields. In the presented paper, comparison of cystoscopy in white light with fluorescence cystoscopy after intravesical administration of 1 g of 5-aminolevulinic acid is presented. METHODS AND RESULTS: From the group of 63 persons examined, no difference between findings in white and blue light was found in 39 cases. In 21 patients more pathological spots were found in blue light (10 cases) or, in agreement with histology, pathology was detected in the blue light only (11 cases). CONCLUSIONS: The intravesical administration of 5-aminolevulinic acid had no side effects. Our study has definitely proved the advantages of fluorescence cystoscopy.

Administration, Intravesical↗

[CEACAM1--a less well-known member of the family of carcinoembryonic antigens].

CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1) is a transmembrane glycoprotein belonging to the carcinoembryonic antigen (CEA) family and immunoglobulin superfamily. It is localized mainly in the apical domains of polarized epithelia, leukocytes and endothelia. With respect to this wide tissue distribution the research is focused on the study of its biological functions. Structural and functional analyses show that the extracellular domain of CEACAM1 participates in homotypic and heterotypic adhesion, whereas the cytoplasmic domain takes part in cell growth inhibition and signal transduction. Whereas CEA is highly expressed in adenocarcinomas, CEACAM1 expression is down regulated in many tumors and its tumor-supressive function was confirmed. CEACAM1 also takes part in insulin metabolism, acts as a promotor of cholesterol crystallization and serves as a binding receptor for certain bacterial strains in humans as well as hepatitis virus in mice.

Animals↗

[Photodynamic diagnosis and therapy in dermatology. Experience with use of TPPS4 in skin diseases].

BACKGROUND: Some skin lesions e.g. basal cell carcinomas are sometimes difficult to remove completely and frequent relapses can develop after their imperfect removal. In case the patient refuses to undergo a radical surgical intervention, more painful alternative like cryotherapy comes into consideration as a method of tumour destruction. Not even such a procedure does guarantee complete destruction of all tumour cells. During the last years new diagnostics and therapeutic methods like photodynamic diagnostic and photodynamic therapy have been developed and they became subjects of our interest. METHODS AND RESULTS: Lesions were treated with photosensitizer (meso-tetra-para-sulphonato-phenyl-porfine-TPPS4) administered in an injection or in the ointment under occlusion. Six to 24 hours later we checked presence of photosensitizer in the lesions and in positive cases we irradiated the lesions with light of suitable wave length (630 nm). CONCLUSIONS: PDD and PDT were used for diagnostics and treatment of different dermatoses (basal cell carcinomas, malignant melanoma metastases, verrucae vulgares, keratoacanthomas, solitary lesions of T lymphoma--mycosis fungoides, m. Bowen, psoriasis vulgaris, pustulosis palmoplantaris, solar keratoma) with very good medical and cosmetic effect. Results are presented in the table. Authors do not consider the PDT to be the only and miraculous method relevant to treatment of all skin tumours or other skin diseases. They are of the opinion that this technique, when properly used, can extend the scale of therapeutic methods. The advantage of PDT is its selectivity, good tolerance and generally good cosmetic effect.

Adult↗

New type of vortex pinning structure effective at very high magnetic fields.

We report on a new type of correlated nanometer-scale pinning structure observed in a melt-processed (Nd0.33Eu0.38Gd0.28)Ba(2)Cu(3)O(y) (NEG-123). It consists of NEG/Ba-rich clusters in the stoichiometric NEG-123 matrix forming a lamellar array with a period of a few nanometers. These lamellas appear within regular twins, thus representing their fine substructure-sometimes straight, sometimes wavy. This new material structure correlates well with the significant enhancement of pinning at high fields, represented by irreversibility field above 14 T at 77 K (B parallel c). We believe that the new pinning medium enables one to significantly broaden the limits for high-field applications.

Journal Article↗

[Photodynamic therapy of benign viral vulvar lesions].

OBJECTIVE: The aim of the study was to evaluate the use of the photodynamic effect in the treatment of genital warts in women. DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynecology, Hospital Na Bulovce, 1st Faculty of Medicine, Charles University, Prague. METHODS: Twenty-five women with genital warts (HPV infection), which were verified by biopsy, were involved into the study. The affected area was treated by ten milligrams of the 5-aminolevulinic acid in three milliliters of gel for 8 hours. Red light with the 630 nanometers wavelength was applied for 15 minutes, with calculated energy intake 30 J/cm2. RESULTS: All women were free of symptoms and had negative colposcopy in the followed period of 3 to 12 months. On average 3.8 sessions were necessary to reach the remission. It was possible to repeat the session after two weeks time. During the application of light, 17 (68%) of the patients felt either no or slight burning sensation, 6 (24%) had unpleasant but bearable sensation and 2 patients had to be treated in short intravenous anesthesia. CONCLUSION: Photodynamic therapy (PDT) is a promising modality in the treatment of HPV vulvar lesions and can be considered to be a method of choice.

Adolescent↗

Role of biliary proteins and non-protein factors in kinetics of cholesterol crystallisation and gallstone growth.

Numerous biliary proteins as well as non-protein factors influence kinetics of cholesterol crystallisation from supersaturated bile. Cholesterol crystallisation pathways, methods used for quantitative evaluation of liquid-to-solid transition of cholesterol in bile and the classical concept of nucleation defect in pathogenesis of gallstones are reviewed in the first part of this article. The relevance of individual biliary proteins and non-protein factors is discussed in the second part. Finally, a new concept according to which accelerated crystallisation of cholesterol inhibits gallstone growth and protects the gallbladder wall from toxic injury resulting from the increased absorption and accumulation of cholesterol from supersaturated bile is suggested.

Animals↗

Immunoaffinity isolation of CEACAM1 on hydrazide-derivatized cellulose with immobilized monoclonal anti-CEA antibody.

Carcinoembryonic cell adhesion molecule 1 (CEACAM1) is a human membrane glycoprotein belonging to the carcinoembryonic antigen (CEA) family and to the immunoglobulin superfamily. It is expressed in apical membranes of many epithelial cells in gastrointestinal and urogenital tract and also in granulocytes and lymphocytes, and its biological effect in human tissues has recently been discussed in literature. The purpose of this study was to isolate CEACAM1 glycoprotein from bile and characterize its purity and recovery which has not been described before. Affinity chromatography of CEACAM1 on hydrazide-activated cellulose with immobilized monoclonal anti-CEA F34-187 antibody is described. The immunoglobulin carbohydrate moiety was oxidized by periodate and then bound to hydrazide-activated matrix. Crude protein fraction from bile was applied on the affinity column and after extensive washing of non-bound proteins CEACAM1 was eluted with 6 M guanidine-HCl. A single immunopositive 85 kDa band was detected on Western blots with anti-CEA antibody after SDS-PAGE. We found out that CEACAM1 was not stainable with any common method of protein staining and the only non-specific method which could detect the 85 kDa band was a lectin staining.

Antibodies, Monoclonal↗

Carcinoembryonic antigen-related cell adhesion molecule 1 is the 85-kilodalton pronase-resistant biliary glycoprotein in the cholesterol crystallization promoting low density protein-lipid complex.

A pronase resistant 85-kd glycoprotein in the Concanavalin A-binding fraction (CABF) of biliary glycoproteins has been reported to act as a promotor of cholesterol crystallization. De Bruijn et al. (Gastroenterology 1996;110:1936-1944) found this protein in a low-density protein-lipid complex (LDP) with potent cholesterol crystallization promoting activity. This study identifies and characterizes this protein. An LDP was prepared from CABF by discontinuous gradient ultracentrifugation. Proteins were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), blotting and immunochemical staining with anti-carcinoembryonic antigen, CEA-related adhesion molecule 1 (CEACAM1) cross-reacting antibodies. Biliary concentrations of CEA cross-reacting proteins were determined in patients with and without gallstones. Two isoforms of CEACAM1 (85- and 115-kd bands), CEA and 2 CEA cross-reacting protein bands of 40 and 50 kd were found in human bile. All bands were also present in CABF, but only a subfraction of the 85-kd band found in the LDP was resistant to digestion with pronase. CEACAM1-85 exhibited potent cholesterol crystallization promoting activity in vitro and accounted for most of the activity in CABF. Total CEA cross-reacting protein concentrations were the same in gallbladder biles from patients with cholesterol and pigment gallstones but only half of those in biles from nongallstone subjects. In conclusion, we have identified the protein component of the cholesterol crystallization promoting LDP to be CEACAM1-85.

Adenosine Triphosphatases↗

Impact of antihypertensive therapy on the skeleton: effects of enalapril and AT1 receptor antagonist losartan in female rats.

No data are available about the effects of AT1 receptor antagonist losartan on the skeleton and there is also little information on the activity of an ACE inhibitor enalapril on bone metabolism. It is widely believed that the vasculature plays an important role in bone remodeling under normal and pathological conditions. We treated 14-week-old female Wistar rats with losartan, enalapril or saline. Administration of the ACE inhibitor enalapril and angiotensin II antagonist losartan had no effect on total malondialdehyde (MDA) in the blood and on urinary excretion of some eicosanoids and their metabolites. The administration of enalapril and losartan in a dose recommended for the treatment of hypertension did not cause significant changes in bone density, the ash and mineral content or morphometric parameters of the femur compared to the values found in control female rats.

6-Ketoprostaglandin F1 alpha↗

Embryotoxicity of TPPS4 and PS 3 photosensitizers in chicken embryo under different light conditions.

Hematoporphyrin derivatives have been recommended for photodynamic therapy of malignant processes. We administered TPPS4, and Photosan 3 (PS 3) in chick embryo in ovo, with or without subsequent blue light (400-550 nm) irradiation. The aim was to analyze and compare the effects of both substances on organogenesis under different light conditions. The embryotoxic effect (embryonic death and malformations) was detected after a single intra-amniotic injection of 5 different doses (0.3 to 300 microg) of TPPS4 or PS 3 at embryonic day 3-5. The beginning of the embryotoxicity range (minimal embryotoxic dose) was determined in non-irradiated embryos to be between 0.3-3.0 microg PS 3 and 3.0-30.0 microg TPPS4. Malformations of surviving embryos were similar after both substances, represented by trunk hyperlordosis combined with incomplete closure of the ventral body wall and protrusion of viscera as consequences of amnion contraction, reduction limb deformities, eye malformations and cleft beak. Ten minutes light irradiation in ovo following two hours after intra-amniotic injection of TPPS4 or PS 3 increased by one order of magnitude their embryotoxic effects. Even dark-ineffective doses became highly embryotoxic. Contraction of the amniotic sac and extraembryonic vessels seemed to be a common mechanism of photosensitizer action.

Abnormalities, Drug-Induced↗

[Prognostic factors and markers of activity in multiple myeloma (results of the Cooperative Group for Diagnosis and Treatment of Multiple Myeloma)].

BACKGROUND: Multiple myeloma (MM) is mostly fatal neoplastic disorder, however, the median survival of 30-40 months does not adequately express the wide spectrum courses of the disease. Therefore better prognostic factors are needed. METHODS AND RESULTS: We analyzed the value of both standard clinical features and cytokines for differential diagnosis, assessment of myeloma activity, prediction of overall survival and duration of remission in a group of 124 patients with MM and in 156 with various monoclonal gammapathies, respectively. The initial levels of Ca2+, LD, Hb, albumin, IL-6, PO4- and creatinine were useful for differentiation of monoclonal gammapathy of undetermined significance from MM. Serum IL-6 correlated with the stage and activity of MM, sIL-6R levels were significantly higher only in stage III and in newly diagnosed myeloma. We did not found the correlation between IL-6 and CRP levels. The usefulness of some standard features for prediction of survival was confirmed (Ca2+, Hb, clinical stage and subclassification A/B according to Durie-Salmon, SB2M > 4 mg/ml, creatinine, LD, ALP) as well as sIL-6R serum level determined both at time of diagnosis and during the course of disease. The prognosis of patients with reversible renal failure and those with intact renal function was not significantly different. Among other features, only serum sIL-6R, measured at time of diagnosis or during the course of disease, had significant predictive value for the assessment of duration of event-free survival in patients with MM. CONCLUSION: Due to short follow-up possible association of high levels of IFN-gamma with better prognosis of MM could not be stated.

Adult↗

Long term treatment of IgA nephropathy with cyclosporine A.

20-50% of patients with IgA nephropathy (IgAN) reach end-stage renal failure. Yet a standard treatment for those with progressive course and/or great proteinuria is lacking. We treated 6 patients with biopsy proven IgAN, proteinuria over 3.5 g/24 h and S-creatinine less than 200 micromol/L non-responding to corticosteroids administered for 3 months. They were given cyclosporine A (CsA) 5 mg/kg bw/day then titrated aiming at a serum concentration of 70-150 ng/mL for one year tapered to discontinuation in 9 months. Prednisone 5-10 mg on alternate days was given with CsA. Proteinuria (g/day) decreased from 4.66 +/- 0.43 to 1.38 +/- 0.29 (p < 0.01) after 1 month and to 0.59 +/- 0.14 (p < 0.001) after 1 year of treatment and remained lower than baseline 2 years from the beginning (1.44 +/- 0.27, p < 0.001). GFR (creatinine clearance) did not change during the first month (1.25 +/- 0.21 mL/s vs 1.38 +/- 0.29 mL/s), but decreased after 1 year (1.05 +/- 0.14 mL/s, p < 0.05). After two years it increased to 1.17 +/- 0.16, NS from baseline. We also calculated the ratio of proteinuria to the GFR (mg/L) to assess the role of hemodynamic changes in the decrease of proteinuria. This ratio was 53.80 + 6.47 before therapy, it decreased after 1 month (11.56 +/- 1.7, p < 0.05) and further after 1 year (6.78 + 1.45, p < 0.01). Three months after discontinuation it was still 14.32 +/- 1.00, p < 0.05 from baseline. In conclusion, CsA significantly lowered moderate to high proteinuria in 6 patients with IgAN. Significant decrease of the proteinuria/GFR ratio suggests some non-hemodynamic mechanism of CsA action. The therapy was well tolerated and side-effects were not so severe as to require CsA withdrawal.

Adult↗

Intestinal colonization leading to fecal urobilinoid excretion may play a role in the pathogenesis of neonatal jaundice.

BACKGROUND: Neonatal hyperbilirubinemia remains of concern because of the potential danger for the central nervous system. Because urobilinogen is a nontoxic derivative of bilirubin, the current study was conducted to examine the fecal excretion of urobilinoids and bilirubin in healthy newborns and infants, as well as their intestinal bacteria capable of reducing bilirubin, to assess a possible relation to serum bilirubin levels during the first weeks of life. METHODS: Bilirubin pigments, urobilinoids, and porphyrins were measured in stools of infants during the first week (group A, n = 60) and between the second week and the first 6 months of life (group B, n = 64). Microbiologic analysis of stools was performed in selected cases and bilirubin-converting activity of isolated bacteria was determined in vitro. RESULTS: Urobilinoids were detectable in stools of 57% of the neonates at day 5, but not before. However, fecal urobilinoid production on that day was only a fraction of that observed in adults (0.07 vs. 0.7-3.6 mg/kg per day), whereas at week 6 it increased significantly to an average of 0.9 mg/kg per day. Microbiologic analysis of neonatal stools revealed two novel bacterial strains of Clostridium perfringens and Clostridium difficile capable of reducing bilirubin to urobilinoids. CONCLUSIONS: Urobilinoids can be detected in stools of 57% of newborns at day 5 after delivery. However, the urobilinoid production during the first week of life is quantitatively insufficient to contribute significantly to the removal of bilirubin. Enhancement of the microbial conversion of bilirubin could decrease the intestinal concentration of bilirubin and may decrease the degree or enhance the removal of neonatal hyperbilirubinemia.

Bacteria↗

Soluble adhesion molecules and cytokines in patients with myasthenia gravis treated by plasma exchange.

Plasma exchange (PE) is an effective therapeutic method used in patients with myasthenia gravis (MG) refractory to common therapy and/or with life-threatening respiratory complications. Except for acetylcholine receptor antibodies (AChRAbs), some other inflammatory mediators possibly activated in MG may also be removed during PE. Serum levels of soluble adhesion molecules (sICAM-1 and sVCAM-1), IL-6 and soluble receptors for IL-2 (sIL-2R), IL-6 (sIL-6R) and TNF alpha (sTNF-R II) were measured in 20 MG patients assigned to treatment with PE. On the basis of the serum levels of AChRAb the patients were subdivided into 2 groups (8 patients with low AChRAb, 12 patients with high AChRAb). Soluble adhesion molecules and cytokines were measured before the first and last PE, at the end of the first PE and in the samples of plasma filtrate obtained during the first PE. Before the first PE patients with MG had higher serum levels of sICAM-1, sVCAM-1, sIL-2R and sTNF-R II than controls. Both after the first PE and during the course of PE, a substantial decrease in serum levels of AChRAb, sICAM-1 and sVCAM-1 was recorded. However, serum levels of sIL-2R and sTNF-R II were not significantly influenced by either a single treatment or during the course of PE. There were high levels of AChRAb, soluble adhesion molecules and soluble cytokine receptors in plasma filtrates too. Patients with high circulating AChRAb had higher serum levels of sICAM-1 and sVCAM-1 than patients with low AChRAb. Increased serum levels of soluble adhesion molecules and soluble cytokine receptors in patients with MG suggest some systemic activation of the immune response which is more pronounced in patients with high circulating AChRAb. PE led to the decrease in serum AChRAb and soluble adhesion molecules due to their effective filtration but, on the other hand, serum levels of soluble cytokine receptors were not influenced by PE, in spite of their effective filtration which is probably counteracted by their increased production, possibly stimulated by the contact of the blood with the synthetic membrane.

Adult↗

[Pronuclear and antinuclear factors in the pathogenesis of cholesterol cholelithiasis].

Contrary to hitherto published results, the authors provided evidence of significant pronucleation activity in the protein fraction which is not linked to concanavaline A. Delipidation or proteolysis markedly reduce the pronucleation activity of this fraction. Albumin was identified as the main protein in this fraction. The lipid-protein complex formed by albumin and lipids had a high pronucleation and crystallization activity in relation to cholesterol. Calcium ions increased the crystalization activity. Complexes formed by proteins and lipids can be vectors of the main pronucleation activity in bile. In investigations of the main cholesterol fraction the authors provided evidence that only part of so-called pronucleation proteins is linked to vesicles--i.e. IgM, IgA and biliary glycoprotein BGP I and II. The authors assume that only proteins firmly linked to vesicles can participate in the process of cholesterol crystallization. Biliary glycoprotein BGP I and II was present in vesicles and when added into a model bile it presented a high pronucleation activity. Biliary glycoprotein is a new hitherto not identified pronucleation protein in bile.

Bile↗