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J Maciejewski

Publications and source records attributed to J Maciejewski.

At least 19 recordsLinked to original sources
PubMed2001

Telomere length dynamics in normal individuals and in patients with hematopoietic stem cell-associated disorders.

The telomere length in nucleated peripheral blood (PB) cells indirectly reflects the mitotic history of their precursors: the hematopoietic stem cells (HSCs). The average length of telomeres in PB leukocytes can be measured using fluorescence in situ hybridization and flow cytometry (flow FISH). We previously used flow FISH to characterize the age-related turnover of HSCs in healthy individuals. In this review, we describe results of recent flow FISH studies in patients with selected hematopoietic stem cell-associated disorders: chronic myelogenous leukemia (CML) and several bone marrow failure syndromes. CML is characterized by a marked expansion of myeloid Philadelphia chromosome positive (Ph+) cells. Nevertheless, nonmalignant (Ph-) HSCs typically coexist in the bone marrow of CML patients. We analyzed the telomere length in > 150 peripheral blood leukocytes (PBLs) and bone marrow samples of patients with CML as well as samples of Ph- T-lymphocytes. Compared to normal controls, the overall telomere fluorescence in PBLs of patients with CML was significantly reduced. However, no telomere shortening was observed in Ph- T-lymphocytes. Patients in late chronic phase (CP) had significantly shorter telomeres than those assessed earlier in CP. Our data suggest that progressive telomere shortening is correlated with disease progression in CML. Within the group of patients with bone marrow failure syndromes, we only found significantly shortened telomeres (compared to age-adjusted controls) in granulocytes from patients with aplastic anemia (AA). Strikingly, the telomere length in granulocytes from AA patients who had recovered after immunosuppressive therapy (recAA) did not differ significantly from controls, whereas untreated patients and nonresponders with persistent severe pancytopenia (sAANR) showed marked and significant telomere shortening compared to healthy donors and patients with recAA. Furthermore, an inverse correlation between age-adjusted telomere length and peripheral blood counts was found in support of a model in which the degree of cytopenia and the amount of telomere shortening are correlated. These results support the concept of extensive proliferation of HSCs in subgroups of AA patients and suggest a potential use of telomere-length measurements as a prognostic tool in this group of disorders as well.

Anemia, Aplastic↗
PubMed2001

[Dietary antioxidants and total antioxidant status in children with nephrotic syndrome].

UNLABELLED: Several studies indicate the pathophysiological importance of reactive oxygen species in patients with nephrotic syndrome (NS). The present study was designed to determine the effect of dietary antioxidants on antioxidant enzymes (SOD, GPX, GR) activity and on total antioxidant status (TAS) in children with nephrotic syndrome. 36 children with NS (19 with first episode and 17 with relapse of NS) aged 4-16 were included into the study. Total antioxidant status was estimated using two-reagent Randox Total Antioxidant Status test in plasma. All patients had normal blood pressure, normal serum creatinine level and ingested a diet appropriate for age (with individual differences). Total antioxidant status was estimated using two-reagent Randox Total Antioxidant Status test in the plasma. Glutathione peroxidase (GPX), superperoxide dysmutase (SOD) and glutathione reductase (GR) activity was using antioxidant kits (Randox). A 3-day dietary intake record was obtained from each patient and then analyzed with computer program FOOD 2.0. Laboratory investigations were performed before steroid treatment. RESULTS: 1) in children with NS TAS was significantly reduced comparing to controls (0.84 +/- 0.14, 1.21 +/- 0.62 mmol/l, p = 0.002), 2) low manganese intake was found to have negative influence on TAS (TAS = 0.38 + 14.252*Mn, p > 0.001). 3) low intake of all components of antioxidant system was found: zinc (5.6 +/- 3.5 mg/kg b.w./24 h vs 8.6 +/- 4.0 mg/kg b.w./24 h), copper (0.021 +/- 0.013 mg/kg b.w./24 h vs 0.044 +/- 0.014 mg/kg b.w./24 h), manganese (0.029 +/- 0.0021 mg/kg b.w./24 h vs. 0.067 +/- 0.023 mg/kg b.w./24 h), vitamin E (0.15 +/- 0.04 mg/kg b.w./24 h vs 0.26 +/- 0.06 mg/kg b.w./24 h) and vitamin C (0.34 +/- 0.17 mg/kg b.w./24 h vs 0.87 +/- 0.19 mg/kg b.w./24 h). CONCLUSION: In children with NS reduced antioxidant protection maybe partly associated with low intake of some vital components of the antioxidant system.

Adolescent↗
PubMed2001

[Multiple bone fractures as a rare complication in a child with chronic renal failure].

Renal osteodystrophy may present with a wide spectrum of bone lesions, ranging from high bone turnover to low bone turnover. The authors present a case of multiple bone fracture in 12 year old boy with chronic renal failure. This boy was hospitalized because of retention of urea. The limping was observed by admision. In the X-rays of the long bones the multiple fracture were detected. The potential causes of these fractures and diagnostic problems were discussed.

Bone Density↗
PubMed2001

The application of electron microscopic morphometry as helpful method in the diagnosis of focal segmental glomerulosclerosis (FSGS) early phase. I. Morphometric electron microscopic studies of renal glomeruli in cases of focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD) and mesangioproliferative glomerulonephritis (GNMES) in children.

Electron microscopy morphometric studies were carried out on material obtained from children with minimal change disease (MCD), mesangioproliferative glomerulonephritis (GNMES) and focal segmental glomerulosclerosis (FSGS). The results indicated that an increase in the volume of the matrix in mesangioproliferative glomerulonephritis was due to an increase in the number of cells. The amount of produced matrix in mesangioproliferative glomerulonephritis was proportional to the number of cells in mesangium (so there is no overproduction of matrix). The ratios of mesangial matrix volume to cell volume and matrix volume to the volume of the entire mesangial region in MCD and GNMES were similar and differed significantly from the ratios found in FSGS. The present findings indicate that morphometric studies may be useful in the early diagnosis of glomerular sclerosis. This is particularly significant in cases where light microscopic examination fails to reveal changes indicative of glomerular sclerosis.

Child, Preschool↗
PubMed2001

The application of electron microscopic morphometry as a helpful method in the diagnosis of focal segmental glomerulosclerosis (FSGS) early phase. II. Clinical usefulness of electron microscopic morphometric studies in cases of minimal change disease (MCD) and mesangioproliferative glomerulonephritis (GNMES) with suspicion of progression into focal segmental glomerulosclerosis (FSGS).

Clinical and morphological analysis (including morphometric studies of electron microscopic material) was made in 15 children with MCD and 15 children with GNMES. In both groups, an early phase of FSGS was suspected on the basis of electron microscopic studies. Moreover, analysis included the results obtained in 13 children with the diagnosis of FSGS and in whom repeated biopsies were performed. In most of them, MCD or GNMES was diagnosed from the first biopsy. In most children in whom electron microscopic studies revealed an increase in matrix area in some mesangial regions, thereby suggesting an early stage of glomerular sclerosis, the results of morphometric studies resembled or were identical to the results obtained from a control group with the established diagnosis of FSGS. These findings indicate that morphometric studies of electron microscopic material are significant. The results, when compared with the clinical data, confirm the usefulness of such a diagnostic procedure.

Child, Preschool↗
PubMed2001

[Electrolyte abnormalities and ventricular arrhythmias in children with mitral valve prolapse].

The aim of this study was to determine plasma concentration of magnesium, potassium, calcium and sodium in children with mitral valve prolapse (MVP) and to establish the relation between electrolyte abnormalities and ventricular arrhythmias (VA). The study group consists of the 113 children with MVP (age +/- SD: 10.7 +/- 4.3 years). The 101 healthy children (age +/- SD: 13.0 +/- 3.2 years) were enrolled into the control group. All patients underwent clinical examination, standard ECG, 24 hr ECG Holter monitoring and echocardiography. Blood samples were taken 3 times in fasting state in separate days. All patients were in sinus rhythm. Cardiac arrhythmias were observed more frequently in children with MVP (53%) than in control group (31%, p < 0.0008). VA were recorded in 39% MVP patients, compared with 13% of the healthy children (p < 0.0001). There were no differences in K, Na and Ca concentrations in children with MVP comparing to control group. Serum Mg concentration was significantly lower in MVP group (0.88 +/- 0.08 mmol/l) comparing to healthy children (0.91 +/- 0.07 mmol/l, p < 0.002). A marked decrease in Mg concentration was recorded in patients with MVP and ventricular arrhythmias compared with those without ventricular arrhythmias (0.83 +/- 0.07 vs 0.90 +/- 0.06 mmol/l, p < 0.0001). This study demonstrates that potentially serious dysrhythmias are common in pediatric patients with MVP. It would appear that ambulatory ECG monitoring should be part of the complete evaluation of children with MVP. Since decreased plasma concentration, magnesium supplementation seems to be a prudent approach in children MVP with frequent ventricular premature beats and in children with ventricular tachycardia.

Adolescent↗
PubMed2000

Protease inhibitors stimulate hematopoiesis and decrease apoptosis and ICE expression in CD34(+) cells.

Highly active retroviral therapy has been associated with a decline in the frequency of cytopenia in patients with human immunodeficiency virus (HIV) infection. This may result from lower hematologic toxicity of newer antiviral drugs and their increased efficacy against HIV-1. Protease inhibitors, in addition to their effects on HIV replication, appear to affect various cellular functions. Recently, it was reported that ritonavir inhibited caspase-1 expression in normal CD4(+) cells. It was hypothesized that protease inhibitors may improve hematopoietic function owing to their direct effects on the bone marrow progenitor cells. When ritonavir was added to methylcellulose cultures of bone marrow cells from HIV-infected patients and normal controls, colony formation increased 2.4-fold (n = 5) in control cultures and 4-fold (n = 5) in cultures of cells from HIV-infected patients. In the presence of ritonavir, cultures of CD34(+) cells showed markedly decreased apoptosis in comparison with untreated cultures (45% decrease in apoptotic cell number; n = 6). A synthetic inhibitor of caspase 1 (Ac-Tyr-Val-Ala-Asp-aldehyde [single-letter amino acid codes]), which inhibits activation of several caspases including CPP32 and interleukin 1beta-converting enzyme (ICE or caspase 1), also decreased the rate of apoptosis and enhanced colony formation by progenitor cells derived from HIV-infected patients (3-fold; n = 5). In ritonavir-treated samples derived from HIV-infected individuals, the number of cells expressing ICE also decreased. In conclusion, HIV protease inhibitors may, by blocking the caspase-dependent apoptotic pathway, overcome inhibition of hematopoiesis seen in patients with HIV infection, an effect unrelated to their antiviral activity. (Blood. 2000;96:2735-2739)

Antiretroviral Therapy, Highly Active↗
PubMed2000

Th1/Th2 balance and CD45-positive T cell subsets in primary nephrotic syndrome.

T cells are involved in the pathogenesis of nephrotic syndrome (NS). The aim of the study was to determine whether the activity of T-helper-1 (Th1) and T-helper-2 (Th2) cells and the distribution of the lymphocyte subsets, namely CD45RA+CD4+ ("naive" helper T cells, suppressor-inducer), CD45RA+CD8+ ("naive" suppressor T cells, suppressor-effector), CD45RO+CD4+ ("memory" helper T cells), are predictive for steroid sensitivity in children with primary NS. These parameters were assessed at the onset of disease, before initiation of steroid therapy. Two groups of NS children were retrospectively formed according to steroid sensitivity (SS) or resistance (SR). The activity of Th1 and Th2 cells was defined by the production of interleukin-2 (IL-2), interferon-gamma, IL-4, and IL-10 in the supernatants of CD4+ T cell cultures activated with autologous monocytes presenting tetanus toxoid (TT). Peripheral lymphocyte subsets were determined using double- or triple-color flow cytometry. In SS children with NS we found a decreased proliferative response of CD4+ T cells to TT stimulation, cytokine synthesis indicating the predominance of Th2 activity, and an increased percentage of activated suppressor-inducer (CD45RA+ CD4+CD25+, 5.18+/-0.8, P<0.001) and suppressor-effector (CD45RA+CD8+CD25+, 2.05+/-0.6, P<0.01) cells, with the concomitant reduction of activated memory cells (CD45RO+CD4+CD25+, 0.2+/-0.1, P<0.001). In children with SRNS we found an increased proliferative response of CD4+ T cells to TT, a rise in activated memory (CD45RO+CD4+CD25+, 3.82+/-0.7, P<0.01) and suppressor-inducer peripheral T cells (CD45RA+ CD4+CD25+, 3.85+/-0.6, P<0.01), but a low percentage of activated suppressor-effector (CD45RA+CD8+ CD25+, 0.5+/-0.2, P<0.05) T cells. We conclude that prior to treatment the distribution of lymphocyte subpopulations in peripheral blood together with Th1 and Th2 cell activity provides a useful tool for evaluating the likelihood of steroid sensitivity in patients with primary NS.

Antigen-Presenting Cells↗
PubMed2000

Cyclophosphamide and other new agents for the treatment of severe aplastic anemia.

Severe aplastic anemia (SAA) has a poor prognosis in the absence of treatment. Current accepted therapeutic strategies include allogeneic stem-cell transplantation and immunosuppression, both resulting in long-term survival in the majority of patients. Although human leukocyte antigen (HLA)-matched sibling stem-cell transplantation is highly effective, the 25% probability of finding a suitable sibling donor within a family renders this approach available to only a minority of patients. Transplantation using HLA-matched, unrelated donors carries a high risk of treatment failure along with considerable toxicity. While combined immunosuppression with both antithymocyte globulin (ATG) and cyclosporine A (CSA) produces hematologic improvement in most patients, relapse is common. Late evolution of aplastic anemia to other serious hematologic disorders, including paroxysmal nocturnal hemoglobinuria (PNH), myelodysplasia, and acute leukemia, is also a significant problem following treatment with ATG/CSA. Recently, results of immunosuppression in SAA with another potent immunosuppressive agent, cyclophosphamide, were reported in a small number of patients. The overall response rate was similar to that seen with ATG/CSA, but relapse and late clonal disease were not observed during a long period of follow-up. A larger randomized trial comparing sustained hematologic response rates to either conventional immunosuppression with ATG/CSA or high-dose cyclophosphamide and CSA is now underway; secondary end points include response duration, event-free survival, and overall survival. Additionally, a number of protocols designed to test the efficacy of alternative immunosuppressive or immunomodulatory agents are being developed.

Anemia, Aplastic↗
PubMed2000

[Total antioxidant status (TAS) in children with nephrotic syndrome].

UNLABELLED: The aim of the study was to estimate total antioxidant status (TAS) as the most reliable factor involved in antioxidant protection in children with nephrotic syndrome. 28 children with NS (12 with first episode and 16 with relapse NS) aged 4-16 were included into the study. TAS was estimated using two-regent Randox Total Antioxidant Status test in plasma. Laboratory investigations were performed before steroid treatment. RESULTS: 1) in children with NS TAS was significantly reduced comparing to controls (0.81 +/- 0.14; 1.21 +/- 0.62 mmol/L; p = 0.002), 2) negative correlation between Tchol and LDL and TAS was found (TAS vs Tchol p = 0.0005, R = 0.61; TAS vs LDL p = 0.03, R = 0.41), 3) TAS was higher in children with the first episode of NS comparing to children with following relapse (0.88 +/- 0.07; 0.75 +/- 0.16; mmol/l; p = 0.14). CONCLUSION: In children with NS reduced antioxidant protection is one of the factors leading to renal injury and may be a consequence a cause reason of lipids abnormalities.

Adolescent↗
PubMed2000

[Resistance to therapy in primary nephrotic syndrome: effect of MDR1 gene activity].

MDR1 gene encodes for a transmembranous glycoprotein, gp-170, which acts as a drug export pump and is also a cyclosporine(CsA)-binding protein. This study aimed at evaluating MDR1 expression in NS sensitive(S) and resistant(R) to therapy (steroids/S/, cyclophosphamide/C/, CsA) patients. Twenty six boys, 13 girls aged 3-8 years were included to the study. MDR1 was analysed using: 1) evaluation of gp-170 activity according to DiC2/3/ [3,3-Diethyloxa-carbocyanine Iodide] by means of flow cytometry and as 2) mRNA expression of MDR1 determined by RT-PCR. The analysis was performed in the lymphocyte subset CD4/CD45RA presenting suppressor-inducer activity. Negative control, Jurkat-T-cell line, not expressing the MDR1 phenotype, was transfected with viral expression vector containing a full-length cDNA for the human MDR1 gene. We found that: in SR-NS the high expression of MDR1 was associated mainly with the suppressor-inducer T-cells (CD45RA+CD4+) and was subsequently enhanced during an ineffective treatment with C and/or CsA. C-R-NS and CsA-R-NS were partially reversible by S- and R-Verapamil; this was in vitro confirmed by inhibition of export pump activity, gp-170. SS-NS, C-S-NS and CsA-S-NS presented the low expression and activity of MDR1 comparing to R-children (p < 0.001) and healthy controls (p < 0.00001). Resistance to therapy in NS patients seems to be resulted from the enhanced expression of MDR1 gene and subsequent high activity of export pump P-gp-170. Calcium channel blockers may reverse the MRD1-related resistance in the therapy of NS. Analysis of MDR1 may help to detect of suspected therapy resistance in NS.

Anti-Inflammatory Agents↗
PubMed2000

[Does the changed Th1/Th2 activity in children with the assessment of body water in children with nephrotic syndrome: initial results].

T cells are involved in the pathogenesis of nephrotic syndrome (NS). The aim of the study was to determine whether the activity of T-helper-1 (Th1) and T-helper-2 (Th2) cells are predictive for steroid sensitivity in children with primary NS. These parameters were assessed at the onset of disease, before initiation of steroid therapy. Two groups of NS children were retrospectively formed according to steroid sensitivity(SS) or resistance(SR). Activity of Th1 and Th2 cells was defined by the production of IL-2, IFN-gamma and IL-4, IL-10 (ELISA), respectively, in the supernatants of the culture of CD4+ T cell cultures activated with autologous monocytes presenting tetanus toxoid (TT). Peripheral lymphocyte subsets were determined using double or triple colour flow cytometry. In SS children with NS we found the cytokine synthesis indicating the predominance of Th2 activity. We conclude that prior to treatment the Th1 and Th2 cell activity provides a useful tool to evaluate the probability of steroid sensitivity in patients with primary NS.

Anti-Inflammatory Agents↗
PubMed1999

Clinical and morphological (including morphometric) aspects of minimal change disease and mesangial glomerulonephritis with unfavourable course in children.

Clinical and morphological analysis was made to assess 9 cases of minimal change disease (MCD) and 30 cases of mesangial glomerulonephritis (GNMES) recognized by light microscopy with unfavourable course. Case selection was based exclusively on the clinical course suggesting a possibility of early sclerosis (long-term steroid resistance, frequent recurrences, rare short-lasting remissions, hypertension, renal failure). It was found that the unfavourable clinical course was clearly more frequently associated with electron microscopic than light microscopic changes. Marked increase of the matrix was observed also in those glomeruli in which light microscopy did not reveal any changes or only the signs of immaturity. It was also noticed that in those cases in which the assessment of mesangial matrix increase (which means the onset of sclerosis) is not certain, it is useful to make a morphometric analysis of electron microscopic material.

Adolescent↗
PubMed1998

Is vacuolization of podocytes and glomerular endothelial cells of prognostic value with respect to FSGS?

Focal segmental glomerulosclerosis (FSGS) poses a major problem both from the clinical and pathomorphological viewpoint. The diagnosis of FSGS in its early stage is vital mainly because of rapidly developing therapeutic modalities. In the literature various changes are discussed which may be of prognostic value (may predict the development of FSGS). One the these changes in vacuolization, mainly of podocytes and less frequently of endothelial cells. The purpose of the present study was to analyse biopsy specimens to find out to what extent vacuolization of podocytes and endothelial cells is associated with FSGS. We compared vacuolization in minimal change disease (MCD), mesangial glomerulonephritis (GNMES) and FSGS. A similar analysis was made also with respect to those cases of MCD and GNMES, in which electron microscopy suggested an early stage of FSGS. In each group electron micrographs obtained from 15 children were analysed. Electron micrographs (12-15 on average) were obtained most frequently from 3 glomeruli. Each case electron micrographs contained 90-100 podocytes. Based upon the same electron micrographs we counted capillary lumina and defined the percentage of those which contained vacuolized endothelia (we counted the capillary lumina, and not the cells, because it is most frequently impossible to identify the border of vacuolized endothelial cells). The number of capillary cross-sections was 60 on average. The results of the analysis were compared with the clinical data. This comparison did not confirm the hypothesis of other investigators that vacuolization is of a prognostic value. Additionally we evaluated the character of vacuoles. Within podocytes the vacuoles were varying in shape. Surrounded by a single membranous layer most frequently they contained material corresponding to proteins or proteoglycans, rarely to lipids. Sometimes the vacuoles were autophagosomal, occasionally they consisted of the dilated rough endoplasmic reticulum. Vacuole-like changes within the capillary lumina were related to the swelling of endothelial cytoplasm or mesangial processes. The reasons for a discrepancy between our results and those reported by other investigators necessitate further studies.

Child↗
PubMed1997

Intravenous aminophylline increases the degree of saturation of urine with calcium phosphate and struvite.

This study was designed to assess the effect of i.v. treatment with aminophylline (AMPH) on the risk of calcium phosphate and struvite stone formation. We administered AMPH in doses of 4 mg/kg body weight in 15-min i.v. infusions to 60 infants with clinical symptoms of obstructive bronchitis with dyspnoea. During 3 hours after infusion we observed a significant increase in urine saturation with brushite, octocalcium phosphate and struvite. This rise in urine saturation may increase the risk of kidney stone formation.

Aminophylline↗