Biomedical subjects

M Nowicki

Publications and source records attributed to M Nowicki.

At least 19 recordsLinked to original sources

PubMed2006

Ezrin--a useful factor in the prognosis of nephrotic syndrome in children: an immunohistochemical approach.

BACKGROUND: Minimal change disease (MCD) and diffuse mesangial proliferation (DMP) are the most common pathomorphological forms of nephrotic syndrome glomerulopathies in children. The clinical course of DMP can be characterised by either DMP-sensitivity (DMP-S) or DMP-resistance (DMP-R) to steroids, resulting in an unfavourable course of the glomerulopathy. Although the clinical processes of DMP-S and DMP-R are initially identical, resistance to steroids may be foreseen by the immunohistochemical expression of cytoskeleton-associated proteins in podocytes. AIMS: To estimate the immunohistochemical expression of ezrin in children with MCD, DMP and focal segmental glomerulosclerosis (FSGS) and to evaluate its usefulness in predicting resistance to steroids. MATERIALS AND METHODS: Renal biopsy specimens of patients with MCD (n = 15), DMP (n = 16) and FSGS (n = 6) were taken. The control tissue consisted of normal-appearing cortex taken from kidneys resected for localised neoplasms (n = 6). The indirect immunohistochemical protocol for the use of a monoclonal antibody directed against ezrin was used. RESULTS: The immunohistochemical expression of ezrin in cases progressively reduced from MCD to DMP-S to DMP-R to FSGS. Except for DMP-R and FSGS (p>0.05), the difference in ezrin expression in podocytes was significant. CONCLUSION: Ezrin can be a potent marker of podocyte injury (podocytopathy) and may help in the histological qualification of MCD, DMP and FSGS. The increased permeability of the filtration barrier in steroid-resistant and proteinuric glomerulopathies may be a consequence of subcellular changes in podocyte-associated proteins following decreased expression of ezrin.

Adolescent↗

PubMed2006

Vascular endothelial growth factor C--a potent risk factor in childhood acute lymphoblastic leukaemia: an immunocytochemical approach.

AIMS: To investigate the immunocytochemical expression of vascular endothelial growth factor C (VEGF-C) and its receptors (VEGFR-2 and VEGFR-3) in childhood acute lymphoblastic leukaemia (ALL) blasts and to determine the possible role of this complex in the pathogenesis and prognosis of ALL. METHODS AND RESULTS: Bone marrow samples were taken from 120 children diagnosed with ALL. An indirect immunocytochemical procedure was performed with the use of monoclonal mouse anti-human antibodies against VEGF-C, VEGFR-2 and VEGFR-3 (diluted 1 : 100). The immunocytochemical expression of VEGF-C was confirmed exclusively in the cytoplasm of ALL lymphoblasts (the mean percentage was 36.4 +/- 7.2). It was absent from the cytoplasm of normal haematopoietic cells in the control group. No VEGFR-2 or VEGFR-3 expression was detected in the children of either the study or control groups. The risk of induction failure or leukaemic relapse was found to be significant in all VEGF-C+ patients (P < 0.0001 and P < 0.02, respectively; Fisher's exact test). CONCLUSIONS: The absence of VEGF-C in blast cells predicts long-lasting remission in all leukaemic children. Our findings also suggest that leukaemic cell invasion, following VEGF-C-driven lymphangiogenesis, could be related to a mediating role of this peptide produced by blast cells themselves.

Adolescent↗

PubMed2006

Selection of different 5' untranslated region hepatitis C virus variants during post-transfusion and post-transplantation infection.

BACKGROUND: Hepatitis C virus (HCV) translation is initiated in a cap-independent manner by an internal ribosome entry site (IRES) located within the 5' untranslated region (5'UTR). Sequence changes in this region could affect translation efficiency and presumably viral replication. AIM: To determine translation efficiency of 5'UTR variants developing during post-transfusion hepatitis C in two immunocompetent subjects and in two immunosuppressed liver recipients with recurrent HCV. METHODS: Sequential samples were screened for 5'UTR changes by single-strand conformation polymorphism followed by cloning and sequencing whenever band pattern suggested sequence changes. 5'UTR variants were tested for IRES activity using a bicistronic dual luciferase expression plasmid transfected into HepG2 and Huh7 cell-lines. RESULTS: In the transfused patients, translation efficiency of 5'UTR variants from early post-transfusion samples was 5.1- to 13.7-fold higher than that of predominant variants found in late follow-up samples. Post-transplant variants in the other two patients had 2.6- to 5.9-fold higher translation efficiency than those present only in pretransplant samples. CONCLUSION: In the immunocompetent host there may be selection of low translation efficiency HCV variants over the course of infection. However, in immunosuppressed subjects the opposite seems to be true as low translation efficiency variants are superseded by high translation efficiency variants.

5' Untranslated Regions↗

PubMed2006

Prognostic value of stage IV neuroblastoma metastatic immunophenotype in the bone marrow: preliminary report.

AIM: To correlate the immunophenotype of metastatic cells in the bone marrow of patients with neuroblastoma with early treatment failure. METHODS: The studies were performed on bone marrow material obtained from children treated in the department of paediatric oncology, haematology, and transplantology, Poznan University of Medical Sciences, Poland from 1996 to 2003. Immunocytochemical analysis of nervous tissue markers (using the immunomax technique) was performed on 108 bone marrow preparations obtained from 36 children diagnosed with neuroblastoma (stage IV with bone marrow metastases). The analysis included expression of PGP 9.5 protein, substance P, chromogranin A, bombesin, galanin, neuropeptide Y (NPY), and vasoactive intestinal peptide in neuroblastoma metastatic cells defined by the expression of neurone specific enolase. RESULTS: Nineteen relapses occurred within 12 months of the end of treatment. Correlation between the various markers studied and early treatment failure, using Fisher's exact test, revealed that chromogranin A and NPY are strong indicators of an unfavourable prognosis in patients with stage IV neuroblastoma (p < 0.001 and p < 0.0002, respectively). CONCLUSION: Determination of metastatic cell immunophenotypes in bone marrow (particularly chromogranin A and NPY) may help establish the short term prognosis in children with neuroblastoma.

Adolescent↗

PubMed2006

The predicting role of substance P in the neoplastic transformation of the hypoplastic bone marrow.

AIMS: To estimate the expression of substance P in the haematopoietic cells of hypoplastic bone marrow and define its relationship with the course of bone marrow hypoplasia. METHODS: Bone marrow specimens were obtained from 42 children with bone marrow hypoplasia who were hospitalised in the Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, Poznan, Poland, between 1996 and 2003. Substance P and Ki-67 expression were evaluated using immunochemical and hybridocytochemical assays. RESULTS: The expression of substance P (as evidenced by both immunocytochemical and hybridisation techniques) was confirmed in the cytoplasm of B lymphocytes in 8 of 11 children who developed acute leukaemia in 45 (SD 12) days. The percentage of substance P-positive cells ranged from 67.6 to 95.8 (mean of 81.5% cells with immunocytochemistry and 84.3% with in situ hybridisation). The risk of development of leukaemia secondary to bone marrow hypoplasia was found to be significant (p<0.001) in those children who expressed substance P in normal-looking lymphocytes at the initial bone marrow evaluation. CONCLUSIONS: The presence of substance P in B lymphocytes of hypoplastic bone marrow may predict its neoplastic transformation. A marked correlation between substance P-positive bone marrow pattern and the expansion of tumour cells may prove the potential value of this oligopeptide in the pathogenesis of leukaemia.

Adolescent↗

PubMed2006

Histology and ultrastructure of the pineal organ in the domestic goose.

The pineal organs of 14-week-old domestic geese were investigated with light and electron microscopy. The pineals consisted of a wide distal part and a narrow middle-proximal one. The glands were attached to the intercommissural region via the choroid plexus. The pineal parenchyma was formed by round or elongated follicles. The follicular wall was composed predominantly by cells immunoreactive with antibodies against hydroxyindolo-O-methyltransferase (HIOMT) or glial fibrillary acid protein (GFAP). They formed two or more layers. HIOMT-positive elements were represented by elongated cells bordering the follicular lumen and oval cells located in the external layer of the follicular wall. These cells were identified in ultrastructural studies as rudimentary-receptor pinealocytes and secretory pinealocytes, respectively. Among rudimentary-receptor pinealocytes two types of cells, designed as A and B, were distinguished due to structural differences. Type A cells extended through the whole follicular wall and showed regular stratified distribution of organelles in well-recognizable zones with rough endoplasmic reticulum, the Golgi apparatus and mitochondria. Type B cells, like type A pinealocytes, contacted the pineal lumen and showed polarity of their internal structure. However, they were markedly shorter than the cells of type A and lacked stratified distribution of organelles. Secretory pinealocytes contained irregularly dispersed organelles. A prominent feature of all types of goose pinealocytes was the presence of numerous dense core vesicles. The population of GFAP-positive cells consisted of ependymal-like supporting cells and astrocyte-like cells.

Acetylserotonin O-Methyltransferase↗

PubMed2006

Postnatal development of the pineal gland in the goat (Capra hircus)--light and electron microscopy studies.

This study was conducted to investigate structural transformations of the goat pineal gland during postnatal development. The pineals of newborn, 4-week-, 4-month-, 1-year- and 3-year-old male goats were prepared for qualitative and quantitative investigations at both light and transmission electron microscopy levels. In the first 4 months after birth, the pinealocytes developed very intensively, which was connected with enlargement of their volume as well as distinct qualitative and quantitative transformations of their cytoplasmic organelles. Parallel to these changes, the pineal parenchyma underwent deep reorganization and the mosaic pattern, characteristic for newborns, disappeared. At the same time the meshwork of blood vessels supporting the goat pineal gland developed conspicuously. From fourth months to one year of postnatal life continuation of the growth of some pinealocyte organelles and very intensive development of all components of the pineal connective tissue were observed. In the three-year-old goats some decrease in the relative volume of most cytoplasmic structures of pinealocytes as well as increase in collagen fibers in stroma were noticed. The investigations established intensive growth of the goat pineal to the age of 4 months, which included mainly some increase in the pinealocyte and their structures. The pineal gland of 4-month- and 1-year-old goats showed morphological features which are considered as symptoms of high secretory activity. The structure of the pineal gland in 3-year-old animals and the changes observed both in their pinealocytes and connective tissue in comparison with 1-year-old individuals point to some decrease in the goat pineal activity in this age.

Animals↗

PubMed2005

Vascular endothelial growth factor (VEGF-C1)-dependent inflammatory response of podocytes in nephrotic syndrome glomerulopathies in children: an immunohistochemical approach.

AIMS: To analyse expression and distribution of vascular endothelial growth factor (VEGF-C1), podocalyxin and synaptopodin within renal tissue in nephrotic syndrome glomerulopathies in children. METHODS AND RESULTS: Renal biopsies performed at the time and in the manner recommended by the World Health Organization. The study group consisted of submicroscopic glomerulonephritis (n = 10), diffuse mesangial proliferation (n = 14) and focal segmental glomerulosclerosis (n = 5). The control tissue consisted of macroscopically normal appearing cortex taken from kidneys resected for localized neoplasms (n = 3). Material for immunohistochemistry was fixed in Bouin's solution and embedded in paraffin. Indirect immunohistochemistry using monoclonal anti-human antibodies directed against VEGF-C1, podocalyxin and synaptopodin was employed. The distribution of markers was quantified by computerized image analysis. In non-sclerosed glomeruli (within podocyte cytoplasm), VEGF-C1 was more expressed in podocytes of all groups (P < 0.0002), while the distribution of synaptopodin was less expressed in all groups (P < 0.0002). There was no statistical difference between all groups in the expression of podocalyxin. CONCLUSIONS: The increased permeability of the filtration barrier in steroid-resistant glomerulopathies may be a consequence of subcellular changes in podocytes resulting from decreased expression of synaptopodin. Moreover, impaired permeability of endothelium could be secondary to increased expression of podocyte-derived VEGF-C1.

Analysis of Variance↗

PubMed2004

Immunocytochemical study on endothelial integrity of saphenous vein grafts harvested by minimally invasive surgery with the use of vascular mayo stripers. A randomized controlled trial.

OBJECTIVES: The aim of this study is to compare the endothelial integrity of saphenous vein grafts harvested by minimally invasive surgery and veins harvested conventionally for coronary artery bypass surgery in 200 participants who were assigned to interventions by using random allocation. DESIGN: Randomized controlled trial. Methods. Immunocytochemistry with anti-CD 31 antibodies and anti-nitric oxide synthase (NOS) antibodies were employed to identify the endothelial integrity. RESULTS: The CD 31 immunostaining showed that the endothelial cell integrity of the minimally invasive harvested veins was preserved in 82+/-13% of the circumference of luminal endothelium, while in conventionally harvested grafts it was reduced to 64+/-15% (p=0.05).> This was associated with the lack of CD 31 expression in vasa vasorum (10 and 18%) in both groups, respectively, (p=0.02). The NOS immunostaining revealed that the endothelial integrity of the minimally invasive harvested grafts was preserved in 96+/-4% of the luminal endothelium circumference as compared to 74+/-10% in conventionally harvested grafts (p=0.05). The percentage of cases with the lack of NOS expression in all vasa vasorum was 12 and 21%, in G1 and G2, respectively, (p=0.02). CONCLUSION: The endothelial integrity of saphenous vein grafts harvested by minimally invasive surgery is better preserved than with the grafts obtained by the conventional manner. This could play an important role in improving vein graft patency rates.

Aged↗

PubMed2004

Acute renal failure: the new perspectives.

This review updates the progress which has been made in the recent years in the field of diagnosis, prevention and treatment of acute renal failure (ARF). Despite the better recognition of the etiology and risk factors of ARF this disease is still characterized by high mortality especially when developing in patients with multi-organ failure. The origin of ARF is clearly multifactorial but its pathomechanism shows many similarities regardless of a cause. Due to the latest achievements in the understanding of the pathogenesis of ARF better preventive and therapeutic strategies are being developed. Some of them have been successfully tested in experimental settings. Surprisingly most of the human studies showed that preventive methods other than simple hydration could not change the course of the disease or even could be harmful. Also the critical issue remains early ARF detection. In turn in cases of fully developed acute tubular necrosis the major concern is to prevent secondary complications and organ failure and to introduce appropriate dialysis therapy. Although not yet supported by a significant reduction in mortality in most severe cases of ARF some progress has been made due to the development of new convective intermittent or continuous renal replacement therapies, notably hemodiafiltration.

Acute Kidney Injury↗

PubMed2003

Incident hepatitis C virus in women with human immunodeficiency virus infection.

Individuals infected with human immunodeficiency virus type 1 (HIV-1) are frequently coinfected with hepatitis C virus (HCV). Acute HCV infection is often asymptomatic and poorly understood. We conducted a historical prospective study of HCV antibody and viremia in plasma samples obtained during 1994-1999 from a cohort of initially HIV-1-infected, HCV-uninfected women and from HIV-1-HCV-uninfected women. Twenty-two (1.5%) of 1517 experienced seroconversion. Of these, 14 (64%) truly acquired a new infection as assessed by enzyme immunoassay response and new-onset viremia. The incidence rate in HIV-1-infected women was 2.7 cases per 1000 person-years; it was 3.3 cases per 1000 person-years in HIV-1-seronegative women (relative risk, 1.21; P=.75). Acquisition of HCV was associated with any history of drug use (P<.01). Five of 12 viremic, seroconverting individuals cleared viremia. Incident HCV infection among HIV-1-infected and HIV-1-uninfected women was low. It was linked to drug use and commonly resolved.

Adult↗

PubMed2003

Substance P--a potent risk factor in childhood lymphoblastic leukaemia.

The study focused on determining the expression of substance P (SP) in neoplastic bone marrow cells in childhood acute lymphoblastic leukaemia (ALL) in terms of its mRNA and the level of protein production. An attempt has also been made to demonstrate a correlation of SP with leukaemia risk factors and treatment failure. The study group comprised 120 children treated for ALL. Expression of SP was examined by in situ hybridisation with a 5'-biotinylated probe and by immunocytochemistry with specific anti-human SP antibody. Out of 80 patients with common ALL, the expression of SP was demonstrated in 33 cases (41.2%). In the group of 24 children with pre-B ALL, the presence of SP was noted in six cases (25.0%). Of 16 patients with T-cell leukaemia, SP expression was demonstrated in 13 cases (81.2%). The percentage of immunopositive cells in the SP-positive cases ranged from 79.8 to 97.3. Treatment failure in the children with ALL was closely related to the expression of SP observed at the beginning of treatment. The results showed a connection between the presence of SP-positive blasts and leukaemia relapse. This may indicate that SP expression, involved in the proliferation of the tumour cells, may represent a novel risk factor in ALL.

Adolescent↗

PubMed2002

Carvedilol does not modulate moderate exercise-induced hyperkalemia in hemodialysis patients.

BACKGROUND AND AIM: Non-selective beta-adrenergic blockers may cause hyperkalemia in patients with end-stage renal failure. In contrast, alpha-adrenergic blockade has been found to decrease the hyperkalemic effect of physical exercise in healthy subjects, although we were unable to confirm this effect in hemodialysis patients. In a crossover design, we studied the effect of carvedilol, a non-selective beta-adrenergic blocker with an additional alpha1-blocking activity, on exercise-induced hyperkalemia in 17 anuric hemodialysis patients. METHODS: All subjects were given either carvedilol (25 mg/day) or placebo for 2 weeks in a random order with a 2-week wash-out period. At the end of each treatment period they underwent a 30-minute exercise test on a bicycle ergometer with a fixed load of 20 W. RESULTS: The treatment with carvedilol caused a significant decrease in blood pressure. Serum potassium before exercise tests was similar (5.37 +/- 0.2 and 5.24 +/- 0.2 mmol/l on carvedilol and placebo, respectively; mean +/- SE). During the exercise, serum potassium increased significantly (p < 0.001 in both tests) and subsequently decreased during 30 minutes of recovery (p < 0.05). The mean rate of potassium increment during the exercise was similar (23.3 +/- 3.3 micromol/l/min on carvedilol and 20.0 +/- 3.6 micromol/l/min on placebo). During recovery, the mean rate of potassium decrement was 5.0 +/- 3.0 micromol/l/min and 6.7 +/- 2.7 micromol/l/min, respectively. Serum sodium, ionized calcium, insulin and plasma renin activity were similar before the exercise tests and did not change during the exercise. CONCLUSION: Carvedilol does not enhance the hyperkalemic effect of moderate physical exercise in anuric hemodialysis patients.

Adrenergic alpha-Antagonists↗

PubMed2002

Distribution of NADPH-diaphorase activity in the pineal gland of the Turkey.

NADPH-diaphorase activity was histochemically demonstrated in the nerve fibers, neuronal-like cell bodies and in the endothelial cells of the vasculature in the pineal gland of the turkey. The nerve fibers were localized in the choroid plexus, connecting the pineal gland with the diencephalon as well as inside the pineal gland, where they formed basket-like structures around the pineal follicles. A group of neuronal-like cell bodies was observed in the proximal part of the gland. The positive staining was not observed in the pinealocytes of rudimentary-photoreceptor type and in the supporting cells.

Animals↗

PubMed2002

Pituitary adenylate cyclase-activating polypeptide-immunoreactive (PACAP-IR) nerve fibers in the pig pineal gland.

The present study demonstrates the occurrence of PACAP-immunoreactive (PACAP-IR) nerve fibers in different compartments of the pig pineal gland, including glandular capsule (where they form a very dense network) and subependymal tissue close to the pineal recess (moderate to dense meshwork of varicose fibers). Furthermore, several varicose fibers penetrate from the capsule into the connective tissue septa and then into the parenchyma, where they form unequally distributed, fine network and, in some cases, basket-like structures around pinealocytes. Some of the PACAP-IR nerve fibers, observed both in the habenular and posterior epithalamic areas, extend to the pineal gland. PACAP-IR cells could be demonstrated neither in the pineal gland, nor in epithalamic areas.

Animals↗

PubMed2001

Discontinuation of potent antiretroviral therapy: predictive value of and impact on CD4 cell counts and HIV RNA levels.

OBJECTIVE: To characterize predictors and consequences of discontinuing antiretroviral therapy (ART) in terms of CD4 cell count, HIV RNA, and reported side-effects in a large cohort of HIV-infected women. DESIGN: Cohort study. METHODS: A total of 1058 HIV-infected women initiated potent ART before September 1999. For each 6 month period after October 1996 we determined the proportion of potent ART users who downshifted to non-potent ART and who discontinued all ART. We examined the role of CD4 cell count and HIV RNA with regard to ART discontinuation. RESULTS: Between October 1996 and September 1999, 1058 individuals contributed 3362 visits at which potent ART was reported in the previous 6 months. Overall rates of 6 month downshifting and discontinuation were 10.0% and 6.7%. The proportion of individuals discontinuing all ART increased from 2.9% in late 1996 to 9.1% in mid 1999 (P < 0.001). Individuals with high HIV RNA levels were more likely to discontinue (P < 0.05). Compared to those who continued on potent ART, individuals who discontinued experienced large declines (P < 0.001) in CD4 cell counts and were more than three times more likely (P < 0.001) to experience HIV RNA increases. However, over one-third of those discontinuing ART reported side-effects and this subset had smaller CD4 cell count declines as compared to discontinuers not reporting side-effects (P = 0.147). CONCLUSIONS: In a large cohort of HIV-infected women, an increasing proportion of potent ART users discontinued ART over 3 years. Higher HIV RNA levels predicted discontinuation. Immediate immunological/virological deleterious consequences were observed. Side-effects were the most common reason for discontinuation and CD4 cell count declines were larger among those who did not cite side-effects as the reason for discontinuation.

Adult↗

PubMed2001

Exposure of hepatitis C virus-negative recipients to > or =2 infected blood donors.

This study analyzed 4 cases of hepatitis C virus (HCV)-naive transfusion recipients who developed hepatitis after receiving blood from >1 HCV-infected donor. One recipient was exposed to 4 donors, 2 were exposed to 3 donors, and 1 was exposed to 2 donors. For 3 recipients, the strain from 1 of the donors predominated in all follow-up samples collected for 8-40 months. For 2 recipients, the strain from the second donor was occasionally detectable with sensitive strain-specific assays. For the fourth recipient, the initially dominant strain was later supplanted by a strain from the other donor. Simultaneous exposure to multiple HCV strains may result in concomitant infection by >1 strain, although a single strain rapidly establishes its dominance. These observations are compatible with the presence of competition among infecting HCV strains that results in the dominance of 1 strain and competitive exclusion or suppression of other strains.

Adult↗

PubMed2001

Hormonal regulation of appetite and body mass in patients with advanced prostate cancer treated with combined androgen blockade.

Cachexia is rarely observed in patients with advanced prostate cancer treated with combined androgen blockade. Androgens play an important role in the regulation of body mass composition and influence the secretion of leptin, the appetite regulating hormone. The aim of the study was to assess the influence of a combined treatment with nonsteroidal antiandrogen and LH-RH analogue on the hormonal regulation of appetite and changes in body mass in patients with advanced prostate cancer (Whitmore-Jewett stage D1 or D2). Eighteen patients with prostate cancer and 17 healthy subjects matched for age and body mass index were included. In all patients serum concentrations of leptin, neuropeptide Y (NPY), insulin, testosterone and estradiol were measured before and after four and twelve weeks of androgen blockade. Pretreatment serum leptin levels were similar in patients with prostate cancer and in the controls. In a multiple regression analysis only body mass index and testosterone significantly contributed to the variation of plasma leptin. During the treatment body mass and plasma leptin significantly increased while NPY decreased. The change of plasma NPY was significant only after 4 weeks of therapy. This study shows that the afferent regulation of leptin secretion is unchanged in advanced prostate cancer. Androgen ablation significantly increases body mass and influences secretion of appetite regulating hormones. Testosterone appears to play a significant role in the regulation of leptin secretion.

Adenocarcinoma↗