The post-war fate of the teaching of Roman Law in the Polish people’s Republic (1944–1989)

The article presents the difficult history of the teaching of Roman law in Poland in the period of 1944–1989. The standards concerning the education of lawyers favoured by the socialist authorities aimed at making it more practical. People’s Poland needed lawyers with the “proper” world-view. At that time the ideology of the socialist regime played a great role in politics. The Soviet ideology rejected Roman law as the law of a slavery-based system in which private property dominated. Consequently, the state socialist authorities in Poland opposed the study of Roman law and tried to eliminate it from the university curriculum. Despite these difficulties and pressures, Roman law as a university subject was still taught in centers of legal education between 1944 and 1975. In 1975, following the reform of law studies in Poland, the subject was incorporated into the history of law curriculum and disappeared as an autonomous discipline for six years. Roman law was reintroduced into the law curriculum in 1981, when universities in Poland gained more freedom in this respect. Since then it has been taught mainly in the first year of studies, though the scope of its teaching has been narrower than it was in the inter-war period. The relation between Socialist law and Roman Law is still an interesting subject, and it is worth a further and more in-depth examination

70. Meningiomas treated in Greatpoland Cancer Center between 1990–1997

IntroductionWe analyzed correlation between age of patient with anaplastic meningiomas, extension of tumor excision, histopatological recognition and time to recurrence and survival.Material and methodsBetween 1990–1997 7 patients with anaplastic meningioma, 3 patients with haemangiopericytoma, 2 patients with sarcoma meningeum (6 women and 6 men) have been irradiated. 7 patients underwent radical excision of the tumor, 5 patients non radical. The patients were irradiated from limited fields to total dose 56–60 Gy/T mostly by energy Co-60 (9 patients) and photons 9 MV (3 patients).ResultsThere are 6 patients with anaplasticum meningioma still alive. 3 patients living 96–108 months, 3 other 30–39 months. Recurrence was confirmed in two male participants who underwent radical surgery in 12 and 29 month from the start of treatment. The first patient died after 16 months with recurrence of the disease. One patient (39 years old) with heamangiopericytoma lives 40 months after radical surgery without evidence of recurrence. Two patients died – one 11 months after radical surgery (41 years old) and the other one (42 years old) 21 months after non radical surgery. Both patients (24 and 59 years old) with sarcoma died (one after 8 months, and the other one after 21 months).ConclusionsPatient with anaplastic meningiomas have long survival. The extension of tumor excision didn’t influence on survival

70 Wyniki leczenia chorych na raka sutka w stadium rozsiewu w materiale Wielkopolskiego Centrum Onkologii

WstępLeczenie chorych na raka sutka w stadium rozsiewu (M1) ma charakter paliatywny. Metody leczenia obejmują radioterapię, chemioterapię, hormonoterapię w monoterapii lub jako leczenie skojarzone. Wyniki leczenia są najczęściej złe. Przedstawiamy wyniki leczenia chorych na raka sutka w stadium rozsiewu leczonych w Wielkopolskim Centrum Onkologii.Materiał i metody95 chorych na raka sutka w stadium M1 leczono w latach 1983–1987 w Wielkopolskim Centrum Onkologii. Wiek chorych wahał się od 29 do 74 lat, średnio 51,5 lat. W grupie 65 chorych pierwszym umiejscowieniem przerzutów był kościec, w dalszej kolejności płuca i wątroba. Większość chorych leczona była cytostatykami lub hormonami, u części zastosowano paliatywną radioterapię. Wyniki leczenia opracowano na podstawie historii chorób i przeprowadzonej katamnezie. Grupę badaną poddano 5-letniej obserwacji.Wyniki8 chorych (8,4%) przeżyło 5 lat od momentu rozpoczęcia leczenia zmian przerzutowych. Średni okres przeżycia w całej grupie wyniósł 13,5 miesiąca.WnioskiPomimo złego rokowania leczeniem systemowym udaje się przedłużyć życie części chorych na raka sutka, u których wystąpiły przerzuty odległe

Dimethylarginine Dimethylaminohydrolase II Overexpression Attenuates LPS-Mediated Lung Leak in Acute Lung Injury

Acute lung injury (ALI) is a severe hypoxemic respiratory insufficiency associated with lung leak, diffuse alveolar damage, inflammation, and loss of lung function. Decreased dimethylaminohydrolase (DDAH) activity and increases in asymmetric dimethylarginine (ADMA), together with exaggerated oxidative/nitrative stress, contributes to the development of ALI in mice exposed to LPS. Whether restoring DDAH function and suppressing ADMA levels can effectively ameliorate vascular hyperpermeability and lung injury in ALI is unknown, and was the focus of this study. In human lung microvascular endothelial cells, DDAH II overexpression prevented the LPS-dependent increase in ADMA, superoxide, peroxynitrite, and protein nitration. DDAH II also attenuated the endothelial barrier disruption associated with LPS exposure. Similarly, in vivo, we demonstrated that the targeted overexpression of DDAH II in the pulmonary vasculature significantly inhibited the accumulation of ADMA and the subsequent increase in oxidative/nitrative stress in the lungs of mice exposed to LPS. In addition, augmenting pulmonary DDAH II activity before LPS exposure reduced lung vascular leak and lung injury and restored lung function when DDAH activity was increased after injury. Together, these data suggest that enhancing DDAH II activity may prove a useful adjuvant therapy to treat patients with ALI

Interference of H-bonding and substituent effects in nitro- and hydroxy-substituted salicylaldehydes

Two intramolecular interactions, i.e., (1) hydrogen bond and (2) substituent effect, were analyzed and compared. For this purpose, the geometry of 4- and 5-X-substituted salicylaldehyde derivatives (X = NO2, H or OH) was optimized by means of B3LYP/6-311 + G(d,p) and MP2/aug-cc-pVDZ methods. The results obtained allowed us to show that substituents (NO2 or OH) in the para or meta position with respect to either OH or CHO in H-bonded systems interact more strongly than in the case of di-substituted species: 4- and 3-nitrophenol or 4- and 3-hydroxybenzaldehyde by ∼31%. The substituent effect due to the intramolecular charge transfer from the para-counter substituent (NO2) to the proton-donating group (OH) is ∼35% greater than for the interaction of para-OH with the proton-accepting group (CHO). The total energy of H-bonding for salicylaldehyde, and its derivatives, is composed of two contributions: ∼80% from the energy of H-bond formation and ∼20% from the energy associated with reorganization of the electron structure of the systems in question

Mutations in Potassium Channel KCND3 Cause Spinocerebellar Ataxia Type 19

OBJECTIVE: To identify the causative gene for the neurodegenerative disorder spinocerebellar ataxia type 19 (SCA19) located on chromosomal region 1p21-q21. METHODS: Exome sequencing was used to identify the causal mutation in a large SCA19 family. We then screened 230 ataxia families for mutations located in the same gene (KCND3, also known as Kv4.3) using high-resolution melting. SCA19 brain autopsy material was evaluated, and in vitro experiments using ectopic expression of wild-type and mutant Kv4.3 were used to study protein localization, stability, and channel activity by patch-clamping. RESULTS: We detected a T352P mutation in the third extracellular loop of the voltage-gated potassium channel KCND3 that cosegregated with the disease phenotype in our original family. We identified 2 more novel missense mutations in the channel pore (M373I) and the S6 transmembrane domain (S390N) in 2 other ataxia families. T352P cerebellar autopsy material showed severe Purkinje cell degeneration, with abnormal intracellular accumulation and reduced protein levels of Kv4.3 in their soma. Ectopic expression of all mutant proteins in HeLa cells revealed retention in the endoplasmic reticulum and enhanced protein instability, in contrast to wild-type Kv4.3 that was localized on the plasma membrane. The regulatory β subunit Kv channel interacting protein 2 was able to rescue the membrane localization and the stability of 2 of the 3 mutant Kv4.3 complexes. However, this either did not restore the channel function of the membrane-located mutant Kv4.3 complexes or restored it only partially. INTERPRETATION: KCND3 mutations cause SCA19 by impaired protein maturation and/or reduced channel function

Flexibility of a biotinylated ligand in artificial metalloenzymes based on streptavidin—an insight from molecular dynamics simulations with classical and ab initio force fields

In the field of enzymatic catalysis, creating activity from a non catalytic scaffold is a daunting task. Introduction of a catalytically active moiety within a protein scaffold offers an attractive means for the creation of artificial metalloenzymes. With this goal in mind, introduction of a biotinylated d6-piano-stool complex within streptavidin (SAV) affords enantioselective artificial transfer-hydrogenases for the reduction of prochiral ketones. Based on an X-ray crystal structure of a highly selective hybrid catalyst, displaying significant disorder around the biotinylated catalyst [η6-(p-cymene)Ru(Biot-p-L)Cl], we report on molecular dynamics simulations to shed light on the protein–cofactor interactions and contacts. The results of these simulations with classical force field indicate that the SAV-biotin and SAV-catalyst complexes are more stable than ligand-free SAV. The point mutations introduced did not affect significantly the overall behavior of SAV and, unexpectedly, the P64G substitution did not provide additional flexibility to the protein scaffold. The metal-cofactor proved to be conformationally flexible, and the S112K or P64G mutants proved to enhance this effect in the most pronounced way. The network of intermolecular hydrogen bonds is efficient at stabilizing the position of biotin, but much less at fixing the conformation of an extended biotinylated ligand. This leads to a relative conformational freedom of the metal-cofactor, and a poorly localized catalytic metal moiety. MD calculations with ab initio potential function suggest that the hydrogen bonds alone are not sufficient factors for full stabilization of the biotin. The hydrophobic biotin-binding pocket (and generally protein scaffold) maintains the hydrogen bonds between biotin and protein

Activated Leukocyte Cell Adhesion Molecule Expression and Shedding in Thyroid Tumors

Activated leukocyte cell adhesion molecule (ALCAM, CD166) is expressed in various tissues, cancers, and cancer-initiating cells. Alterations in expression of ALCAM have been reported in several human tumors, and cell adhesion functions have been proposed to explain its association with cancer. Here we documented high levels of ALCAM expression in human thyroid tumors and cell lines. Through proteomic characterization of ALCAM expression in the human papillary thyroid carcinoma cell line TPC-1, we identified the presence of a full-length membrane-associated isoform in cell lysate and of soluble ALCAM isoforms in conditioned medium. This finding is consistent with proteolytically shed ALCAM ectodomains. Nonspecific agents, such as phorbol myristate acetate (PMA) or ionomycin, provoked increased ectodomain shedding. Epidermal growth factor receptor stimulation also enhanced ALCAM secretion through an ADAM17/TACE-dependent pathway. ADAM17/TACE was expressed in the TPC-1 cell line, and ADAM17/TACE silencing by specific small interfering RNAs reduced ALCAM shedding. In addition, the CGS27023A inhibitor of ADAM17/TACE function reduced ALCAM release in a dose-dependent manner and inhibited cell migration in a wound-healing assay. We also provide evidence for the existence of novel O-glycosylated forms and of a novel 60-kDa soluble form of ALCAM, which is particularly abundant following cell stimulation by PMA. ALCAM expression in papillary and medullary thyroid cancer specimens and in the surrounding non-tumoral component was studied by western blot and immunohistochemistry, with results demonstrating that tumor cells overexpress ALCAM. These findings strongly suggest the possibility that ALCAM may have an important role in thyroid tumor biology