[Report from the Scientific Symposium: Risk management for control of antibiotic resistance"].
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Biomedical subjects
Publications and source records attributed to B Urban.
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Abnormal isoforms of the prion protein (PrP(Sc)) that cause prion diseases are propagated and spread within the body by "carrier" cell(s). Cells of the immune system have been strongly implicated in this process. In particular, PrP(Sc) is known to accumulate on follicular dendritic cells (FDCs) in individuals affected by variant Creutzfeld-Jakob disease. However, FDCs do not migrate widely and the natural history of prion disorders suggests other cells may be required for the transport of PrP(Sc) from the site of ingestion to lymphoid organs and the central nervous system. Substantial evidence suggests that the spread of PrP(Sc) requires bone marrow-derived cells that express normal cellular prion protein (PrP(C)). This study examined the expression of PrP(C) on bone marrow-derived cells that interact with lymphoid follicles. High levels of PrP(C) are present on myeloid dendritic cells (DCs) that surround the splenic white pulp. These myeloid DCs are ontologically and functionally distinct from the FDCs. Consistent with these observations, expression of PrP(C) was strongly induced during the generation of mature myeloid DCs in vitro. In these cells PrP(C) colocalized with major histocompatibility complex class II molecules at the level of light microscopy. Furthermore, given the close anatomic and functional connection of myeloid DCs with lymphoid follicles, these results raise the possibility that myeloid DCs may play a role in the propagation of PrP(Sc) in humans.
A case of tuberous sclerosis in a 5-year old boy with ocular manifestations and other organ abnormalities (dermatologic, neurologic, renal pathology) is presented. Ophthalmological changes (astrocytic hamartomas of the retina, gelatinous tumor, vascular sheathing) are described. Differential diagnosis is presented.
We report on the molecular characterisation of two novel granule proteins of the protozoon and human pathogen Entamoeba histolytica. The proteins, which were named grainin 1 and 2, show a considerable structural similarity to calcium-binding proteins, particularly within EF-hand motifs. Each grainin possesses three of these putative calcium-binding sites. Based on careful inspection of known structures of protein families containing EF-hands, a domain of grainin 1 covering two EF-hand motifs was modeled by homology. Calcium-binding activity of grainins was demonstrated by two independent methods. These granule proteins may be implicated in functions vital for the primitive phagocyte and destructive parasite such as control of endocytotic pathways and granule discharge.
We have extended the exploration of microscopic dynamics of supercooled liquids to small wave numbers Q corresponding to the scale of intermediate range order, by developing a new experimental approach for precise data correction for multiple scattering noise in inelastic coherent neutron scattering. Our results in supercooled Ca0.4K0.6(NO3)(1.4) reveal the first direct experimental evidence, after a decade of controversy, that the so-called picosecond process around the glass transition corresponds to a predicted first, faster stage of the structural relaxation. In addition, they show that this process takes the spatial form of fast heterogeneous collective flow of correlated groups of atoms.
OBJECTIVE: The purpose of this study was to determine whether CT can be used to distinguish serous cystadenomas from mucinous cystadenomas or cystadenocarcinomas of the pancreas and play an enhanced role in patient triage and treatment. MATERIALS AND METHODS: A blinded retrospective analysis of CT scans from 50 patients with pathologically proven primary cystic pancreatic neoplasms was performed independently by three radiologists. Using classic CT criteria as reported in the literature, each tumor was categorized as definitely serous, mucinous, or indeterminate. Tumor location, size, presence of calcification, and size of largest cyst were recorded. Data for each reviewer were analyzed independently. Consensus data were then subjected to multivariate logistic regression analysis. RESULTS: The ability of our reviewers to diagnose serous neoplasms ranged from 23% to 41%. Eight mucinous neoplasms were mistaken for serous tumors by two of the three reviewers. When consensus between at least two of the three reviewers was used for diagnosis, 27% of serous neoplasms were correctly diagnosed and all of the mucinous tumors were correctly identified as uncertain or mucinous, yielding the same clinical end point. For multivariate logistic regression analysis, a cyst smaller than 2 cm had a statistically significant association (p = 0.005) with serous tumors, and the presence of peripheral tumoral calcification had a statistically significant association (p = 0.01) with mucinous tumors. CONCLUSION: There is significant variability in the CT appearance of serous and mucinous neoplasms of the pancreas, making CT an insensitive tool for differentiating these tumors. All tumors with peripheral calcifications were identified as mucinous neoplasms.
The authors present a case of 16-year old boy with unilateral neurochorioretinitis induced by toxocariasis. Quick diagnosis and effective treatment allowed to obtain clinical improvement.
PURPOSE: The evaluation of contrast sensitivity in children and adolescents with type I diabetes mellitus with and without retinopathy, taking into account metabolic control. MATERIAL AND METHODS: We examined 100 young patients (71 without retinopathy and 29 with background retinopathy on fluorescein angiography) and 60 control non-diabetic subjects matched for age and sex, without visual or systemic symptoms. Contrast sensitivity was measured in spatial frequency of 3, 6, 12 and 18 cycles/degree (c/d). RESULTS: Contrast sensitivity was significantly lower (p < 0.001) in four spatial frequencies in all diabetic patients and in IDDM patients without retinopathy than in control group. Patients with IDDM and retinopathy had abnormal contrast sensitivity at spatial frequency 18 c/d when compared with patients without retinopathy. There was no correlation between contrast sensitivity and HbA1c values. CONCLUSIONS: Contrast sensitivity measurement in children and adolescents with type I diabetes is useful in the evaluation of the nature of early abnormalities in retinal function of diabetics.
PURPOSE: The evaluation of changes in ophthalmoscopic examination and fluorescein angiography in children and adolescents with insulin dependent diabetes mellitus. MATERIAL AND METHODS: 100 patients with type I diabetes mellitus aged 9.3-21.5 years (15.76 +/- 2.69), with diabetes duration of 1-13.5 years (6.57 +/- 2.52) were examined. RESULTS: Retinal changes in ophthalmoscopic examination were observed in 12 cases. Fluorescein angiography allowed to detect diabetic retinopathy in 29 patients. There was no correlation between the incidence of retinopathy and the age of patients. Vascular abnormalities were related to the duration of diabetes. Retinopathy was not found in children < 10 years of age.
Whether changes of cardiac high-energy phosphate concentrations occur over the cardiac cycle remains controversial. The hypothesis was that such cyclical changes are accentuated during acute or chronic myocardial stress. Isolated rat hearts were perfused under four conditions: (1) control, (2) inotropic stimulation by doubling of perfusate [Ca2+], (3) acute hypoxia (buffer PO2 approximately 150 torr), and (4) failing, chronically infarcted hearts. 31P-MR spectra were obtained at seven time points of the cardiac cycle. Under control conditions, cyclical changes ("cycling") of ATP (11+/-3%*, *P < 0.05) and phosphocreatine (9+/-2%*) were detected, inorganic phosphate cycling did not reach statistical significance. At high [Ca2+] perfusion, cycling of phosphocreatine (9+/-5%*) was not accentuated, cycling of ATP and inorganic phosphate did not reach significance. During acute hypoxia, cycling of ATP (10+/-4%*) and inorganic phosphate (11+/-4%*) occurred, but cyclical changes of phosphocreatine were not significant. In chronically infarcted hearts, the extent of cyclical changes of ATP, phosphocreatine, and inorganic phosphate was not accentuated. Thus, in perfused rat heart, small oscillations of high-energy phosphates during the cardiac cycle are detectable, but such changes are not accentuated during acute or chronic stress. The concentrations of high-energy phosphates over the cardiac cycle are tightly regulated.
Little is known about the regulation of total creatine concentration in heart, skeletal muscle, brain, liver and kidney in response to increased dietary creatine intake. The phosphorylated fraction of intracellular creatine (phosphocreatine) remain relatively constant, and therefore, higher intracellular creatine levels may increase the energy reserve of the heart [phosphocreatine and phosphoryl transfer via creatine kinase (CK)] and of other organs. To test the effect of supplying exogenous creatine on the myocardial energy reserve and on creatine content of various organs, rats were given chow containing 0 (Untreated), 1, 3, 5, or 7% (of diet weight) creatine for ;40 days. Thereafter, hearts were perfused and left ventricular developed pressure and heart rate were recorded. High-energy phosphate concentrations were determined with 31P-NMR spectroscopy, CK reaction velocity by 31P-magnetization transfer. Total creatine was determined in heart, skeletal muscle, brain, liver, kidney and serum by high-performance liquid chromatography (HPLC). Creatine feeding increased serum creatine by 73% (1% creatine), 142% (3%), 166% (5%) and 202% (7%). In the heart, increased serum creatine levels did not affect mechanical function; ATP, phosphocreatine, inorganic phosphate, CK reaction velocity and total creatine were all unchanged. Total creatine also remained constant in brain and skeletal muscle, while creatine content increased 4.6-fold in the liver and 1.9-fold in the kidney. We conclude that myocardial energy reserve via CK cannot be increased by exogenous creatine treatment.
Endothelin-1 (ET-1) is the most potent vasoconstrictor known to date, and it was proposed that this peptide plays a major role in myocardial ischemia/reperfusion injury. ET-1 could increase myocardial susceptibility to ischemia by two mechanisms: via coronary flow reduction and/or via direct, metabolic effects on the heart. In isolated, buffer-perfused rat hearts, function was measured with a left ventricular balloon, and energy metabolism (ATP, phosphocreatine, inorganic phosphate, intracellular pH) was estimated by 31NMR-spectroscopy. Under constant pressure perfusion, hearts were subjected to 15 min of control perfusion, 15 ("moderate injury") or 30 ("severe injury") min of global ischemia, followed by 30 min of reperfusion. Hearts were pre-treated with ET-1 (boluses of 0.04, 4, 40 of 400 pmol) 5 min prior to ischemia. In the control period, ET-1 reduced coronary flow, ventricular function, phosphocreatine and intracellular pH dose-dependently: during ischemia/reperfusion, coronary flow, functional recovery and high-energy phosphate metabolism were adversely affected by ET-1 in a dose-related manner. To study effects of ET-1 not related to coronary flow reduction, additional hearts were perfused under constant flow conditions (ET-1 0 or 400 pmol) during 15 min of control, 15 min of ischemia and 30 min of reperfusion. When coronary flow was held constant, functional and energetic parameters were similar for untreated and ET-1 treated hearts during the entire protocol, i.e. the adverse effects of ET-1 on function and energy metabolism during ischemia/reperfusion were completely abolished. In both constant pressure and constant flow protocols, 400 pmol ET-1 reduced the extent of ischemic intracellular acidosis. The authors conclude that ET-1 increases the susceptibility of isolated hearts to ischemia/reperfusion injury via reduction of coronary flow.
A peptide corresponding to the epidermal growth factor homology domain of beta-heregulin stimulated autophosphorylation of the heregulin receptors erbB2 and erbB3 in Schwann cells and activation of the mitogen-activated protein (MAP) kinases ERK1 and ERK2. Heregulin-dependent activation of PAK65, a component of the stress-activated signaling pathway, ribosomal S6 kinase, and a cyclic AMP (cAMP) response element binding protein (CREB) kinase, identified as p95(RSK2), was also observed. Receptor phosphorylation and activation of these kinases in response to heregulin occurred in the absence of forskolin stimulation and were not augmented in cells treated with forskolin, a direct activator of adenylyl cyclase. Schwann cell proliferation in response to heregulin was observed only when the cells were also exposed to an agent that elevates cAMP levels. In the absence of heregulin, elevation of cAMP levels failed to stimulate Schwann cell proliferation. Forskolin significantly enhanced heregulin-stimulated expression of cyclin D and phosphorylation of the retinoblastoma gene product. In cells treated with both heregulin and forskolin there was a sustained accumulation of phospho-CREB, which was not observed in cells treated with either agent alone. Heregulin and forskolin synergistically activated transcription of a cyclin D promoter construct. These results demonstrate that heregulin-stimulated activation of MAP kinase is not sufficient to induce maximal Schwann cell proliferation. Expression of critical cell cycle regulatory proteins and cell division require activation of both heregulin and cAMP-dependent processes.
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Entamoeba histolytica is susceptible to complement attack in its lumen-dwelling state and develops complement resistance during pathogenic tissue invasion. As experimental evidence suggests that this change in phenotype is accompanied by a change in gene expression, we constructed a subtractive cDNA library to identify genes involved. Poly(A) + RNA from complement-sensitive trophozoites was subtracted from single stranded cDNA derived from complement-resistant ones. Transcripts enriched in the library were found to code for a putative polypeptide comprising all sequence elements characteristic for serine/threonine protein kinases. The gene contains an intron of 46 nucleotides and two polyadenylation sites. Northern-blot analyses confirmed that the gene is expressed in both tissue-derived and laboratory-grown forms of complement-resistant E. histolytica.
PURPOSE: Analysis of cataract surgery with intraocular lens implantation in children and youth performed between 1990 and 1995 in Bialystok University Eye Clinic. MATERIALS AND METHODS: Twenty patients between 5 and 19 years of age were operated. The subjects comprised 15 cases of traumatic and 5 of congenital cataract. Intraocular lens implantation was performed as a primary procedure in 18 patients and as a secondary procedure in 2 cases. RESULTS: Visual acuity of 5/50 to 5/12 was achieved in 14 patients and 5/10 to 5/5 in 6 patients. Posterior capsule opacification requiring YAG-laser capsulotomy was found in 12 patients (60%). CONCLUSIONS: Intraocular lens implantation may be a safe and effective technique for optical correction in children with traumatic and congenital cataracts.
The authors described symptoms of Rubinstein-Taybi syndrome and presented a treatment of this disease. It concerned a 1-year-old baby with obstruction of left lacrimal ducts, psychomotor retardation and facial abnormalities.
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