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M Krasovec

Publications and source records attributed to M Krasovec.

At least 19 recordsLinked to original sources
PubMed2001

Serum concentration and circadian profiles of cathepsins B, H and L, and their inhibitors, stefins A and B, in asthma.

BACKGROUND: In order to determine the effect of asthma on serum concentrations of cathepsins B, H and L, and stefins A and B, the circadian and concentration profiles were followed in steroid-independent and steroid-dependent asthmatics before and after 1-week treatment with methylprednisolone and cyclosporin A. METHODS: Serum samples were taken at 4-h intervals throughout a 24-h period. Cathepsin and stefin concentrations were assayed using specific ELISAs. Data were analysed by one-way ANOVA and least squares fit of 24-h cosine. RESULTS: Temporal analysis of these proteins revealed little or no significant changes with time over a 24-h period. In comparison to normal sera, cathepsin H concentrations were elevated in all asthmatic patients, concentrations of both stefins were decreased in steroid-independent asthmatics, and stefin A concentrations were increased in steroid-dependent asthmatics before therapy. The effect of methylprednisolone treatment was demonstrated on decreased cathepsin B and increased cathepsin L concentrations in post-therapy serum samples. On the other hand, cyclosporin A treatment led to increased concentrations of cathepsins H and L. However, concentrations of stefins A and B were unaffected. CONCLUSIONS: This study associated alterations in balance of serum cysteine proteinases and their inhibitors in asthmatic patients, which has raised the possibility of their involvement in asthma pathogenesis. Validated rhythms of cathepsins and stefins in asthmatic sera exhibited temporal differences, which are too small to influence the time of sampling for their quantitative measurement over the course of a day.

Adult↗
PubMed2001

Circadian and concentration profile of cathepsin S in sera from healthy subjects and asthmatic patients.

Cathepsin S (CS) has been proposed to be associated with asthma pathogenesis but its exact role is not established. In order to understand this proposed association our objective was to follow the 24-h concentration pattern of CS in sera from apparently healthy subjects and from steroid-independent and steroid-dependent asthmatics before and after one weeks' treatment with methylprednisolone (MP) and cyclosporin A (CsA), respectively. Blood samples were collected every 4 h over a 24-h period. Statistical evaluation of data for time effect was performed by one way ANOVA and least-squares fit of 24-h cosine. Little or no significant change of CS concentrations with time over a 24-h period was observed in healthy and asthmatic sera. CS concentrations were significantly lower in steroid-independent asthmatics compared to controls while there was no difference between healthy subjects and steroid-dependent asthmatics. After one week of therapy MP decreased CS concentrations while CsA had no effect. Our data suggest the involvement of CS in asthma pathogenesis and the potential use of CS levels as an additional biological parameter for monitoring the extent of disease and response to therapy.

Adult↗
PubMed2001

Cathepsin B/cystatin C complex levels in sera from patients with lung and colorectal cancer.

A sandwich-type ELISA has been developed for quantification of the complex between the cysteine proteinase cathepsin B (CB) and its reversible tight-binding inhibitor cystatin C (CC) in normal and pathological sera. The assay is based on a combination of catching Ab (3E1), raised against CB, and a horseradish peroxidase-labelled detection Ab (1A2), raised against CC. Only the CB/CC complex is able to evoke a signal in this assay. The detection limit of the assay was 15.5 nM and the working range between 31.3-200 nM. The within and between-run coefficients of variance (CV) varied from 4.7% to 9.4% and 11% to 12.8%, respectively, demonstrating satisfactory reproducibility of the method. The concentration of the CB/CC complex was determined in sera from 90 healthy controls, 32 patients with non-cancerous lung diseases, 148 patients with lung and 32 patients with colorectal cancer. The CB/CC complex was significantly less abundant in sera of patients bearing malignant lung tumours than in those with non-cancerous lung diseases or healthy controls (p<0.001). In colorectal cancer sera its level was significantly lower in advanced stages C and D than in early Dukes' stages A and B (p=0.02). Our results show that the increased levels of CB in malignant sera are not impaired effectively by CC and support the hypothesis of hindered inhibitory capability during cancer progression.

Case-Control Studies↗
PubMed2001

[Allergic contact dermatitis to cosmetics containing Melaleuca alternifolia (tea tree oil)].

INTRODUCTION: Melaleuca alternifolia is a coniferous tree found in tropical regions, the needles contain an essential oil that is used in medical and cosmetic products. The essential oil contains turpentines (limonene, alpha-pinene, phellandrene) that are potentially allergenic. PATIENTS AND METHODS: In 1997, 1216 patients were patch tested in our dermatoligic unit. Fourteen of them tested because of eczema used products containing tea tree oil. The patients used creams, hair products and essential oils containing Melaleuca alternifolia for cosmetic reasons and to treat skin affections. They were patch tested for a standard panel of allergens, topical emulgators, perfumes, plants, topical medications, metal, gloves, topical disinfectants and preservatives, dental products and rubber derivatives. Products containing Melaleuca alternifolia were tested concentrated or diluted. RESULTS: We report on 7 cases of patients with an allergic contact dermatitis due to tea tree oil. Two of them also exhibited from a delayed type IV hypersensitivity towards fragrance-mix or colophony suggesting the possibility of cross reaction or an allergic group reaction caused by contamination of the colophony with the volatile fraction of turpentines. DISCUSSION: The allergic potential of low concentrations of Melaleuca alternifolia is presumed to be low on healthy skin. Photoaged Melaleuca alternifolia must be considered to be a stronger sensitizer.

Adult↗
PubMed2000

Serum cystatin C, a potent inhibitor of cysteine proteinases, is elevated in asthmatic patients.

The effect of asthma pathogenesis on serum cystatin C, a potent inhibitor of cysteine proteinases and a newly proposed marker of the renal function, has not been yet determined. The objectives were to determine the 24-h pattern of cystatin C and creatinine concentrations in sera of asthmatic patients in order to test whether their concentrations might reflect circadian rhythms, the disease severity and the effect of therapy. Serum concentrations of cystatin C and creatinine were determined in steroid-independent and steroid-dependent asthmatics before and after 1 week of treatment with methylprednisolone and cyclosporin A, respectively. Samples were collected every 4 h during a 24-h period. Little or no significant effects of time on cystatin C and creatinine concentrations over a 24-h period were observed in healthy and asthmatic sera. However, significantly higher cystatin C concentrations were found in asthmatic patients compared to controls which suggests its role in the pathogenesis of asthma. Methylprednisolone increased and cyclosporin A decreased serum cystatin C concentrations after 1 week of therapy. Additionally these results support the need for the evaluation of cystatin C as a marker of glomerular filtration rate determination in asthma.

Adrenal Cortex Hormones↗
PubMed2000

Cysteine proteinase cathepsin H in tumours and sera of lung cancer patients: relation to prognosis and cigarette smoking.

In order to evaluate the role of cysteine peptidase cathepsin H (Cath H) in human lung cancer its protein levels were determined in 148 pairs of lung tumour tissue and adjacent non-tumourous lung parenchyma using the enzyme-linked immunosorbent assay technique. Additionally, Cath H levels were determined in sera of 171 patients with malignant tumours, 34 patients with benign lung diseases and 47 healthy controls. The median level of Cath H in tumour tissue was 0.64 times that in the corresponding lung parenchyma. Relating tumour levels with histological type we found higher Cath H levels in small-cell and adenocarcinomas and lower levels in squamous cell carcinoma, large-cell carcinoma and secondary tumours. A significant difference in Cath H level between lung tumour tissue and non-tumourous lung parenchyma was associated with the group of cigarette smokers (156 vs 263 ng mg(-1) protein, P < 0.001). For this group of patients Cath H tumour levels correlated with the survival rate, while for the entire patient population this was not the case. Smokers with high tumour levels of Cath H experienced poor survival. Cath H was significantly higher in sera of patients with malignant and benign lung diseases than in control sera (P < 0.001). The increase was significant for all histological types, being the highest in small-cell and squamous cell carcinomas. Our study reveals that in lung tumours there is different behaviour of Cath H compared with other cysteine peptidases, e.g. cathepsin B and cathepsin L. Variations between tissue and serum levels of Cath H indicate either reduced expression or enhanced secretion of this enzyme in lung tumours.

Carcinoma, Non-Small-Cell Lung↗
PubMed2000

Cysteine proteinase inhibitors stefin A, stefin B, and cystatin C in sera from patients with colorectal cancer: relation to prognosis.

The levels of cysteine proteinase inhibitors stefin A, stefin B, and cystatin C were determined using ELISAs in sera obtained preoperatively from 345 patients with colorectal cancer and in control sera from 125 healthy blood donors. The levels of stefin A and cystatin C were found to be moderately increased in patient sera (1.4-fold and 1.6-fold, respectively; P < 0.0001), whereas the level of stefin B remained statistically unchanged when compared with controls. The medians were 4.3 ng/ml versus 3.2 ng/ml for stefin A, 1.2 ng/ml versus 1.7 ng/ml for stefin B, and 679 ng/ml versus 425 ng/ml for cystatin C. In patient sera, a weak correlation of cystatin C with age (r = 0.34; P < 0.001) and gender (P = 0.01) was found. Stefin A and cystatin C levels were independent of Dukes' stage, whereas stefin B correlated significantly with Dukes' stage, its level being the highest in stage D (P < 0.007). Stefin B and cystatin C correlated with survival, whereas stefin A was not a significant prognostic factor in this study. Using medians as cutoff values, patients with high levels of stefin B and patients with high levels of cystatin C exhibited a significantly higher risk of death than those with low levels of inhibitors (hazard ratio = 1.6; 95% confidence interval, 1.2-2.2; P = 0.002 for stefin B; hazard ratio = 1.3; 95% confidence interval, 1.0-1.8; P = 0.04 for cystatin C). Our results reveal a correlation between high levels of extracellular cysteine proteinase inhibitors and short survival in patients with colorectal cancer, and the data thus support previous studies suggesting a contributing role of protease inhibitors in the progression of cancer.

Adult↗
PubMed1999

[Acne and its treatment possibilities].

Acne is a multifactorial disease affecting the pilosebaceous follicles. It is a treatable condition for which the aims of therapy are to reduce social isolation and to prevent or minimise scarring. Propionibacterium acnes is an anaerobic bacterium strongly implicated in the pathogenesis of acne. A gradual increase in the resistance of P. acnes to many antibiotics has been documented in the last decade, and there is thus a growing need to use either appropriate antibiotics or even change the therapeutic strategy in favour of other regimens, i.e. isotretinoin, antiandrogens. A treatment guide is presented and the side-effects of these regimens are discussed.

Acne Vulgaris↗
PubMed1999

Immunochemical analysis of cathepsin B in lung tumours: an independent prognostic factor for squamous cell carcinoma patients.

In order to evaluate the possible role of the proteolytic enzyme cathepsin B (cath B) in human non-small cell lung cancer (NSCLC) we examined cath B concentrations (cath B(C)) and activities (cath B(A)) in homogenates of 127 pairs of lung tumour tissues and corresponding non-tumourous lung parenchyma. Total cath B activity (cath B(AT)) and enzymatic activity of the fraction of cath B, which is stable and active at pH 7.5 (cath B(A7.5)) were determined by a fluorogenic assay using synthetic substrate Z-Arg-Arg-AMC. The immunostaining pattern of cath B was determined in 239 lung tumour tissue sections, showing the presence of the enzyme in tumour cells (cath B(T-I)) and in tumour-associated histiocytes (cath B(H-I)). The median levels of cath B(AT), cath B(A7.5) and cath B(C) were 5.6-, 3.2- and 9.1-fold higher (P < 0.001), respectively, in tumour tissue than in non-tumourous lung parenchyma. Out of 131 tissue sections from patients with squamous cell carcinoma (SCC), 59.5% immunostained positively for cath B, while among the 108 adenocarcinoma (AC) patients 48.2% of tumours showed a positive reaction. There was a strong relationship between the levels of cath B(AT), cath B(A7.5), cath B(C) and cath B(T-I) in the primary tumours and the presence of lymph node metastases. Significant correlation with overall survival was observed for cath B(T-I) and cath B(A7.5) (P < 0.01 and P < 0.05, respectively) in patients suffering from SCC. In these patients positive cath B in tumour cells (cath B(T-I)) and negative cath B in histiocytes (cath B(H-I)) indicated significantly shorter survival rate compared with patients with negative cath B(T-I) and positive cath B(H-I) (P < 0.0001). In contrast, in AC patients, both, positive cath B(T-I) and positive cath B(H-I), indicated poor survival probability (P < 0.014). From these results we conclude that the proteolytic enzyme cath B is an independent prognostic factor for overall survival of patients suffering from SCC of the lung.

Adenocarcinoma↗
PubMed1998

[Temporary roentgen epilation after embolization of a cerebral arteriovenous malformation].

A patient with a large left-sided arteriovenous malformation underwent superselective angiography and therapeutic embolization. Sixteen days later he presented with an acute anagen-dystrophic hair loss localized to the occipital and right parietal regions corresponding to the irradiated scalp area. The diagnosis of an acute radiation injury to the hair follicle from prolonged fluoroscopic imaging during the interventional neuroradiologic procedure was made. This reversible side effect occurs typically after single short-term exposures of 300-400 cGy. Above single doses of 1200 cGy, the epilation is permanent. Patients have to be informed about the possibility of this reversible complication, which must be distinguished from alopecia areata, postoperative ischemic pressure alopecia and drug toxicity.

Adult↗
PubMed1998

Prognostic significance of cathepsins B and L in primary human breast cancer.

PURPOSE: Evaluation of the clinical significance of cytosolic tumor levels of the lysosomal cysteine proteases cathepsin B (catB) and cathepsin L (catL) in patients with primary breast cancer. PATIENTS AND METHODS: CatB (n = 1,500) and catL (n = 1,391) levels were determined by enzyme-linked immunosorbent assay (ELISA) in cytosols routinely prepared from frozen-tissue samples that were submitted to our laboratory for the assessment of steroid-hormone-receptor status. The median duration of follow-up of patients still alive at the time of analysis was 93 months. RESULTS: Relating catB and catL levels with classical prognostic factors, the proteases were positively correlated with the number of positive lymph nodes (P < .01), and negatively with the level of steroid-hormone receptors (P < .01). We did not find a significant relationship between catB or catL levels with age and menopausal status of the patients or with the size of the primary tumor. The levels of catB and catL were positively correlated with each other and with the rates of relapse and death (all, P < .0001). In multivariate regression analysis for relapse-free survival (RFS) and overall survival (OS), corrected for the contribution of age/menopausal status, tumor size, the number of positive lymph nodes, and steroid-hormone-receptor status, catB and catL were significant predictors of the rates of relapse and death (all, P < .01). No statistically significant interactions of catB or catL with any of the classical prognostic factors or with each other were observed in their associations with the rates of relapse and death. CONCLUSION: CatB and catL levels measured in routinely prepared cytosols are strong parameters to predict the rate of relapse and the length of survival after treatment of the primary breast tumor.

Adult↗
PubMed1998

Prognostic values of cathepsin B and carcinoembryonic antigen in sera of patients with colorectal cancer.

The level of cathepsin B (Cat B) was determined in sera obtained preoperatively from 325 patients with colorectal cancer using an ELISA. Control sera from 90 healthy blood donors were analyzed. The levels of Cat B detected included all forms that were present in the sera, i.e., mature enzyme, precursor molecule, and enzyme-inhibitor complexes. The level of Cat B was significantly increased in sera of patients with colorectal cancer. The median level was 10.7 ng/ml versus 2.1 ng/ml in controls (P < 0.0001). A correlation between Cat B serum level and advanced Dukes' stage (P < 0.003) was found, whereas no associations have been found with age, sex, or level of carcinoembryonic antigen (CEA). In survival analysis, the patients with high serum Cat B experienced significantly lower survival probability. At the optimal cutoff value of 9.4 ng/ml, the relative hazard ratio was 1.8 (95% confidence interval, 1.1-2.8; P = 0.016) in the univariate Cox proportional hazards model. The median observation time was 4.4 years (range, 3.2-5.5 years). In multivariate analysis, Dukes' stage was the strongest prognostic variable, followed by age, whereas serum Cat B and CEA were not significant prognostic factors in this model, in accordance with their association with Dukes' stage. When the data for Cat B and CEA were combined, CEA-positive patients were further separated by Cat B into high- and low-risk groups. Patients with high serum levels of both molecules had significantly shorter survival (relative hazard ratio of 2.2; 95% confidence interval, 1.5-3.2; P < 0.0001), as compared with patients with low levels of both molecules.

Adult↗
PubMed1997

Lupus profundus/panniculitis.

A 25-year-old Caucasian woman developed two areas of tender panniculitis on her left thigh. While one lesion ulcerated, the other showed no overlying cutaneous changes. Histological examination showed lymphocytic perivascular and periappendageal infiltrates, and direct immunofluorescence revealed granular immunoglobulin deposits at the dermal-epidermal junction in the skin overlying the lesions. Laboratory tests revealed lymphopenia, anemia and an increased blood sedimentation rate. The serology for syphilis was false positive. For several months the patient had also been suffering from arthralgia with palpable synovitis of the wrist and several interphalangeal joints. Overall, these clinical findings are consistent with the diagnosis of lupus profundus/panniculitis associated with mild systemic LE.

Adult↗