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Biomedical subjects

A Kowalska

Publications and source records attributed to A Kowalska.

At least 19 recordsLinked to original sources

Induction of senescence in MYCN amplified neuroblastoma cell lines by hydroxyurea.

Recently, it was shown that MYCN amplified cells spontaneously expulse extrachromosomally amplified gene copies by micronuclei formation. Furthermore, it was shown that these cells lose their malignant phenotype and start to age. We tested whether it is possible to encourage neuroblastoma tumor cells to enter the senescence pathway by low concentrations of the micronuclei-inducing drug hydroxyurea (HU). We studied the effect of HU on 12 neuroblastoma cell lines with extra- or intrachromosomally amplified MYCN copies and without amplification. Two extrachromosomally amplified neuroblastoma cell lines (with double minutes) were investigated in detail. Already after 3 weeks of HU treatment, the BrdU uptake dropped to 25% of the starting cells. After 4 weeks, enlarged and flattened cells (F-cells) and increased granularity in the majority of cells were observed. A drastic reduction of the MYCN copy number-down to one copy per cell-associated with CD44 and MHCI upregulation in up to 100% of the HU treated neuroblastoma cells was found after 5-8 weeks. Telomere length was reduced to half the length within 8 weeks of HU treatment, and telomerase activity was not detectable at this time, while being strongly expressed at the beginning. All these features and the expression of senescence-associated-beta-galactosidase (SA-beta-GAL) in up to 100% of the cells support the hypothesis that these cells entered the senescence pathway. Thus, low-dose HU is a potent senescence elicitor for tumor cells with gene amplification, possibly representing an attractive additional strategy for treatment of this subset of tumors.

Antineoplastic Agents↗

Factors influencing the maintenance of nicotine abstinence among the habitants of the region of Lódź and Kalisz in the years 1996-2003.

The aim of the study was to determine the factors allowing non-smoking for the next 2 years after a 5-year period of non-smoking. A questionnaire study was performed in October 2003 among 449 of men and women chosen from among 1700 contest' 'Quit & Win' Competition participants, which was ending in 1996 2nd International Antinicotine Campaign "Quit & Win" in Poland in the region of Lódź and Kalisz. Chosen people were respondents, who during studies conducted in the years 1998 and 2001 stated that they were not smoking at all since their participation in the contest. Filled-in questionnaires were sent back by 296 people (65.9%). The analysis showed that the surveyed with elementary education more rarely than people with other level of education could preserve in non-smoking habit for the next 2 years after a 5-year period of non-smoking. Further maintenance of nicotine abstinence was not dependent on: age, sex, the place of living, the marital status and the source of income.

Adult↗

Cell cycle and cell size regulation in Down syndrome cells.

Although the neuropathological features typical for Down Syndrome obviously result from deregulation of both, cell cycle control and differentiation processes, so far research focused on the latter. Considering the known similarities between the neuropathology of Down Syndrome and Alzheimer's disease and the knowledge, that in Alzheimer's disease neuronal degeneration is associated with the activation of mitogenic signals and cell cycle activation, it is tempting to investigate the consequences of an additional chromosome 21 on mammalian cell cycle regulation. We analysed the distribution of cells in different cell cycle phases on the flowcytometer and the cell size of human amniotic fluid cells with normal karyotypes and with trisomy 21. We could not detect any significant differences suggesting that the presence of an additional copy of the about 225 genes on human chromosome 21 does not trigger cell cycle effects in amniotic fluid cells. These data provide new insights into the cell biology of trisomy 21 cells.

Amniotic Fluid↗

Iodine-induced hyperthyroidism--an epidemiological survey several years after institution of iodine prophylaxis in Poland.

In 1997, the obligatory model of iodine prophylaxis was introduced in Poland in order to correct the existing status of mild and/or moderate iodine deficiency. In order to monitor possible side-effects of increased iodine supply, studies on iodine-induced hyperthyroidism were initiated by establishing several regional registers of hyperthyroidism. In the present paper, the results of a two-year monitoring (2000-2001) have been summarized. There are no epidemiological data on hyperthyroidism prior to starting the iodine prophylaxis, but the obtained current data are comparable to observations in other countries, made after iodine supplementation. The incidence of iodine-induced hyperthyroidism did not exceed the acceptable level, thus confirming--together with previous observations on the effectiveness of iodine prophylaxis--the adequacy of applied dose of KI (30 microg/kg NaCl), used for salt iodization in Poland.

Adult↗

Familial frontotemporal dementia and parkinsonism with a novel mutation at an intron 10+11-splice site in the tau gene.

We report a case of familial frontotemporal dementia and parkinsonism characterized by early onset with mental retardation. The patient died at the age of 54; neuronal loss was severe in the frontal and temporal cortices, globus pallidus, substantia nigra, red nucleus and dentate nucleus. Anti-tau-positive fibrillary changes were observed in neurons and glia in these regions. Although the patient had 2 novel point mutations of the tau gene, P301P (CCG to CCA) and an intron 10+11-splice site (T to C), exon trapping analysis indicated that the latter was pathogenic.

Brain↗

Ability of patients to accurately recall the severity of acute painful events.

OBJECTIVE: Pain studies require prospective patient enrollment to ensure accurate pain assessment. The authors correlated pain assessments of an acute painful episode over a one-week period and determined the accuracy of patient pain severity recall over time. METHODS: This was a prospective, descriptive, longitudinal study. Participants were a convenience sample of 50 emergency department patients with acute pain resulting from injuries or painful invasive procedures. A trained research assistant administered a structured pain survey containing demographic and historical features to all patients. Patients sequentially assessed their pain severity using a vertical 100-mm visual analog scale marked "most pain" at the top, a verbal numeric rating scale ranging from 0 to 100 from none to worst (NRS100), and a verbal numeric rating scale ranging from 0 to 10 from none to worst (NRS10). Patients were contacted by phone and asked to reassess their initial pain severity one and seven days later using the two verbal numeric rating scales. Analysis of pain assessments using the various scales at the three time intervals was performed with Pearson's and Spearman's coefficients and repeated-measures analysis of variance (ANOVA). RESULTS: There were 50 patients with a mean age of 41 years. Correlation between initial pain assessments on the three scales ranged from 0.83 to 0.92. Correlations between the initial and 24-hour assessments were NRS100-0.98 and NRS10-0.98. Correlations between the initial and one-week assessments were NRS100-0.96 and NRS10-0.97. Repeated-measures ANOVA showed no significant change in pain assessments over time for both verbal numeric scales. CONCLUSIONS: Pain severity assessments of acute painful events one and seven days later were similar and highly correlated with initial assessments using both verbal numeric scales. Patients accurately recall the severity of an acute painful episode for at least one week after its occurrence, which may allow retrospective pain assessments.

Acute Disease↗

The suitability of DNA extracted from formalin-fixed, paraffin-embedded tissues for double differential polymerase chain reaction analysis.

Formalin-fixed, paraffin-embedded (FFPE) tissues are one of the popular sources of diagnostic materials, the easiest to store and transport. They are often used as the source of nucleic acids for retrospective molecular analyses based on DNA amplification by polymerase chain reaction (PCR). However, it is known that nucleic acids from paraffin-embedded tissues are much worse templates than those recovered from fresh tissues. It is exceptionally important in a quantitative analysis, including double differential PCR (ddPCR). Therefore, a pilot study comparing quantity and quality of DNA extracted with various paraffin removal and DNA isolation procedures from FFPE tissues was conducted. Furthermore, the suitability of DNA isolated with optimized procedure for the assessment of erbB-2 average gene copy number (AGCN) was checked. Specimens for comparison of extraction and isolation procedures were generated from the same human normal thyroid tissue embedded in paraffin to eliminate variabilities in tissue processing and sample size. Three procedures of paraffin removal and three procedures of DNA extraction from deparaffinized tissue were compared. Only one procedure provided DNA, which was efficiently amplified in ddPCR. The material obtained with this optimized procedure was used to check the precision of ddPCR by evaluation of AGCN of erbB-2 oncogene. Low variability of obtained results close to expected AGCN value (AGCN=1) indicates high reproducibility of the method, as well as its high accuracy, if the normal value of erbB-2 AGCN in the examined tissue is assumed.

DNA↗

[Clinical-pathomorphologic preparation of patients after surgical treatment of differentiated thyroid cancer to adjuvant treatment with 131I].

UNLABELLED: Thyroid cancer treatment includes: surgery, radioiodine therapy, thyroxine therapy and radiotherapy. Selection of treatment's strategy depends on histopathological evaluation, age of patient and iodine uptake. The aim of the analysis was to verify how the medical documentation of patients treated by surgical treatment was prepared. All patients were directed to the Department of Endocrinology, Holycross Cancer Center in Kielce. Analysis encompassed 33 patients classified to 131I therapy for the first time. In each case patient's medical documentation and histopathological diagnosis made in Department of Tumor Pathology, Holycross Cancer Center, were compared. RESULTS: A conformity with primary cancer diagnosis was obtained in all but one patient in whom pathological consultation did not confirm oxyphilic carcinoma. In four cases the type of cancer was changed as a result of repeated consultation. pTMN classification was stated in 23 primary pathologic examination cases. After consultation of slides and inspection of surgery protocol, total or partial pTNM stage was obtained in other 9 patients. CONCLUSIONS: Establishment of diagnostic and therapeutic algorithm, accepted on Conference in Szczyrk, 1995 is inadequately executed in small centers. Routine consultation of histopathological slides creates a possibility to make a proper choice of treatment's strategy.

Humans↗

Thyroid gland dysfunctions during antiviral therapy of chronic hepatitis C.

BACKGROUND: The aim of this study was assessment of the frequency of thyroid dysfunctions (TD) during antiviral treatment of chronic hepatitis C (CHC). MATERIAL AND METHODS: Data obtained from 120 not treated before patients with CHC, confirmed by the liver biopsy, and with the correct initial thyroid function, was analyzed. 63 patients were treated with IFN-alpha, and 57 with IFN + ribavirin combined therapy. HCV genotype was determined in 80 patients, and alleles HLA DRB1 in 74. Both tests were carried out by the use of commercial assay InnoLipa (Innogenetics, Belgium). All the patients had TSH level regularly monitored every 4 weeks. If any abnormalities were observed, the whole set of tests was applied for diagnosis. Frequency of TD was analyzed according to patients' sex, therapy scheme, HCV genotype and HLA DBR1 alleles. Both groups, with TD and without TD were compared by the initial data, such as: patients' sex, age, ALT activity, and liver biopsy results. RESULTS: TD occurred in 40 patients (33.3%): in 7 (5.8%) signs of hypothyroidism, and in 33 (27.5%) hyperthyroidism. In 14 patients (11.7%) autoimmunological thyroiditis was diagnosed, in 2 (1.7%) subacute thyroiditis, and in the rest of patients only temporary changes in TSH concentration, without any clinical manifestations, were observed. In 4 women, the antiviral treatment was withdrawn, because of thyreotoxicosis, and in 6 patients thyroid hormones supplementation was needed after termination of interferon application. Thyroid complications occurred significantly more often in women than in men. No significant differences according to the age, therapy scheme, ALT activity, fibrosis stage, nor HCV genotype were find in the TD frequency. Among 13 genotyped DRB1 alleles, differences were observed only in DRB*11 allele frequency: in 37.7% of patients with TD, and in 9.1% of patients without TD (p = 0.0093; Pc = 0.12). CONCLUSIONS: Antiviral treatment induces more often latent and transient thyroid dysfunctions as well as autoimmunological, and subacute thyroidis. The last mentioned complication may be the indication for withdrawal of the treatment, or may cause persistent hypothyroidism. Regular monitoring of TSH concentration, in 4-weeks intervals, seems to be essential for early diagnosis of thyroid complications.

Adult↗

Two brothers with frontotemporal dementia and parkinsonism with an N279K mutation of the tau gene.

OBJECTIVE: To characterize the clinical diagnostic features, neuropathologic phenotype of tau deposition, and subunit structure of tau filaments in patients who had an asparagine-to-lysine substitution at codon 279 (the N279K missense mutation) of the gene for microtubule-associated tau protein. BACKGROUND: The N279K mutation is a causative genetic defect for pallidopontonigral degeneration in an American kindred that presents with frontotemporal dementia (FTD) and parkinsonism. METHODS: The authors analyzed retrospectively the clinical symptoms of two Japanese brothers who carry this mutation. Postmortem neuropathologic and electron microscopic studies, and Western blot analysis of insoluble tau were performed to correlate tau-mediated lesions with neurologic deficits. RESULTS: Both patients exhibited impairment in recent memory, parkinsonism, and corticospinal disturbances in addition to FTD. Parkinsonism in one patient was responsive temporarily to l-dopa. There was intense tau deposition in the medial temporal cortices and upper and lower motor neurons with accompanying corticospinal tract degeneration. Two distinct tau isoforms with four microtubule-binding repeats, in hyperphosphorylated forms, were the primary constituents of insoluble tau, which aggregated to the filamentous component, termed "paired tubules," in neurons, oligodendrocytes, and astrocytes. The elemental filaments were hollow tubules measuring 11 to 12 nm in diameter, two of which adhered to each other along their longitudinal axes to form "paired tubules." CONCLUSIONS: Early memory loss and pyramidal signs, which are atypical of FTD, can be presenting symptoms in this disorder. The authors demonstrated that the subunit structure of tau filaments is a pair of hollow tubules despite the prevailing twisted ribbon model.

Amino Acid Substitution↗

Familial frontotemporal dementia with a P301L tau mutation in Japan.

We have reported the family line with frontotemporal dementia (FTD) in Japan. This family line has so far included four patients. Patient II-1 (man) had a 10 year history of slowly progressive personality and behavioral changes and died at the age of 56. His neuropathological examination showed severe atrophy of the bilateral frontal and temporal cortices with neuronal loss, gliosis and superficial spongiosis. Pick bodies were not found. The neuropathological diagnosis was atypical Pick's disease without Pick bodies or Pick-type in FTD. Patient III-2 is patient II-1's oldest daughter and was taken ill with personality change at the age of 52. She died at the age of 68. Patient III-4 is patient II-1's second daughter. Her onset with strange speech and behavior was at the age of 59. Patient III-5 is patient II-1's oldest son. He also had onset with personality change at the age of 54 and had the P301L mutation in tau. In all III generation cases CT/MRI revealed circumscribed frontotemporal atrophy. Patient III-5's PET/SPECT showed signs of hypoperfusion or hypometabolism in the bilateral frontotemporal areas. This is the first report of familial FTD with the P301L mutation in Japan.

DNA Mutational Analysis↗

A Polish pedigree with Alzheimer's disease determined by a novel mutation in exon 12 of the presenilin 1 gene: clinical and molecular characterization.

The presenilin 1 (PS-1) gene, recently identified on chromosome 14q24.3, is a major gene involved into the autosomal dominant forms of early onset Alzheimer's disease (EOAD). Mutations of the PS-1 gene are responsible for the majority of familial EOAD. We found a novel mutation in a Polish family with EOAD from the Poznań region. The mutation at codon 424 in exon 12 of the PS-1 gene leads to an amino acid substitution Leu-Arg in a transmembrane domain VIII of the presenilin 1 molecule. The change is predicted to have a drastic effect on the protein function because it is associated with a very early age of onset (a range of 30-35 years) and a quick progression (about a 4-5 years duration) of the disease.

Adult↗

Comparison of patient and practitioner assessments of pain from commonly performed emergency department procedures.

STUDY OBJECTIVE: To compare patient and practitioner assessments of pain associated with commonly performed emergency department procedures and use of anesthetics before these procedures. METHODS: This was a prospective, observational, cross-sectional study conducted at a university-based ED with a convenience sample of ED patients. Research assistants recorded the procedure performed and historical and demographic information on standardized data collection instruments. After each procedure, both the patient and practitioner independently recorded assessments of patient pain on a 100-mm visual analog scale (VAS). Use of preprocedure anesthetics and patient preferences regarding their use were also identified. Categorical variables were analyzed by chi(2) tests. Patient and practitioner VAS scores were compared using a paired t test; alpha was preset at .05. Correlation coefficients were calculated to assess correlation between patient and practitioner pain scores. RESULTS: A total of 1,171 procedures were evaluated for the 15 most common procedures performed. The mean patient age was 42.8+/-18.7 years and 46.1% were male. Overall, the mean patient VAS was 20.8 mm+/-25.1 mm; the mean practitioner VAS was 23.5 mm+/-20.3 mm. The mean difference between groups was 3.0 mm (95% confidence interval [CI], 1.3 to 4.1). Correlation between patient and practitioner pain scores for individual procedures was poor to fair (r=.26 to.68). The most painful procedures according to patients in descending order were nasogastric intubation, abscess drainage, fracture reduction, and urethral catheterization. Local anesthetics were administered in 12.8% of procedures yet would be requested before similar future procedures by 17.1% of patients. Patients who would choose local anesthetics in the future gave higher pain scores than those who would not (43.3 mm versus 16.3 mm; mean difference=27.0 mm, 95% CI, 22.2 to 31.8 mm). CONCLUSION: The most painful procedures for ED patients were nasogastric intubation, incision and drainage of abscesses, fracture reduction, and urethral catheterization. Although practitioners also identified these procedures as most painful, the correlation between patient and practitioner pain assessments in individual patients was highly variable. Overall use of anesthetics before these procedures was low. Practitioners should be attentive to their patients' individual anesthetic needs before performing painful procedures.

Adult↗

[The value of radiological examination in the diagnosis of rotator cuff tear].

The aim of this paper was to evaluate the correlation between radiological changes on a-p radiograph of the shoulder and rotator cuff tear on the ground of analysis of 328 patients (360 shoulders) aged between 11 and 73 years suffering from different forms of periarthritis humeroscapularis. Sonographic examination revealed rotator cuff tear in 54 shoulders; 38 confirmed at surgery and 16 at arthrography. There was very strong correlation between rotator cuff tear and irregularities of greater tubercle, narrowing of the distance between humeral head and acromion to 5 mm or less, greater tubercle recession, osteophytes and reverse shape of acromion. Last 3 changes were very strongly correlated with medium and large size rotator cuff tear.

Adolescent↗

[Left ventricular diastolic function evaluated by Doppler echocardiography in coronary artery disease in relation to to systolic function].

The aim of the study was to assess the relationship between left ventricular (LV) diastolic dysfunction measured by Doppler mitral flow indices (D.m.f.i.) and LV systolic performance in coronary artery disease (CAD). 107 pts with confirmed CAD without or after MI in I, II NYHA class was divided into 2 groups according to ejection fraction (EF) value = 55%. 13 D.m.f.i. regarding to the time, velocity, flow volume and derivates were calculated. In the patient with CAD with normal EF, the diastolic dysfunction was characterised by the impaired relaxation. There were prolonged isovolumic relaxation time IVRT and deceleration time of early filling flow DT, reduced early filling fraction EFF and increased the atrial filling fraction AFF, decreased E/A ratio and E/A-VTI. The regression analysis revealed the positive correlation between EF and DT r = 0.35 and inverse correlation between wall motion score index WMSI and DT r = DT r = -0.33. The stepwise regression analysis revealed that EF and WMSI are independent factors influencing on DT. Our results confirm that diastolic dysfunction precedes the systolic dysfunction in CAD. The correlation between D.m.f.i. and LV systolic function parameters were obtained. The results suggest that the LV systolic function should be take to account in the Doppler mitral flow analysis.

Adolescent↗

Syndromic foramina parietalia permagna.

We report on a boy with unique somatic and skeletal manifestations. The syndrome consists of branchial and auricular fistulae, abnormal face, and skeletal abnormalities including foramina parietalia permagna.

Abnormalities, Multiple↗

Screening for presenilin-1 gene mutations by PCR-SSCP analysis in patients with early-onset Alzheimer's disease.

The majority of early-onset familial Alzheimer's disease (EOAD) has been associated with mutations in a novel gene on chromosome 14 which has been termed presenilin-1 gene. We screened for mutations within the presenilin-1 gene in twenty patients with EOAD using a PCR-SSCP analysis. We found three aberrant (mutant?) band patterns for exons 4 and 7 in three unrelated patients.

Adult↗