Novel and recurrent variants of ATP2C1 identified in patients with Hailey-Hailey disease.

Hailey-Hailey disease (HHD) is a rare, late-onset autosomal dominant genodermatosis characterized by blisters, vesicular lesions, crusted erosions, and erythematous scaly plaques predominantly in intertriginous regions. HHD is caused by ATP2C1 mutations. About 180 distinct mutations have been identified so far; however, data of only few cases from Central Europe are available. The aim was to analyze the ATP2C1 gene in a cohort of Polish HHD patients. A group of 18 patients was enrolled in the study based on specific clinical symptoms. Mutations were detected using Sanger or next generation sequencing. In silico analysis was performed by prediction algorisms and dynamic structural modeling. In two cases, mRNA analysis was performed to confirm aberrant splicing. We detected 13 different mutations, including 8 novel, 2 recurrent (p.Gly850Ter and c.325-3 T > G), and 6 sporadic (c.423-1G > T, c.899 + 1G > A, p.Leu539Pro, p.Thr808TyrfsTer16, p.Gln855Arg and a complex allele: c.[1610C > G;1741 + 3A > G]). In silico analysis shows that all novel missense variants are pathogenic or likely pathogenic. We confirmed pathogenic status for two novel variants c.325-3 T > G and c.[1610C > G;1741 + 3A > G] by mRNA analysis. Our results broaden the knowledge about genetic heterogeneity in Central European patients with ATP2C1 mutations and also give further evidence that careful and multifactorial evaluation of variant pathogenicity status is essential.

The power of the Mediator complex-Expanding the genetic architecture and phenotypic spectrum of MED12-related disorders.

MED12 is a member of the large Mediator complex that controls cell growth, development, and differentiation. Mutations in MED12 disrupt neuronal gene expression and lead to at least three distinct X-linked intellectual disability syndromes (FG, Lujan-Fryns, and Ohdo). Here, we describe six families with missense variants in MED12 (p.(Arg815Gln), p.(Val954Gly), p.(Glu1091Lys), p.(Arg1295Cys), p.(Pro1371Ser), and p.(Arg1148His), the latter being first reported in affected females) associated with a continuum of symptoms rather than distinct syndromes. The variants expanded the genetic architecture and phenotypic spectrum of MED12-related disorders. New clinical symptoms included brachycephaly, anteverted nares, bulbous nasal tip, prognathism, deep set eyes, and single palmar crease. We showed that MED12 variants, initially implicated in X-linked recessive disorders in males, may predict a potential risk for phenotypic expression in females, with no correlation of the X chromosome inactivation pattern in blood cells. Molecular modeling (Yasara Structure) performed to model the functional effects of the variants strongly supported the pathogenic character of the variants examined. We showed that molecular modeling is a useful method for in silico testing of the potential functional effects of MED12 variants and thus can be a valuable addition to the interpretation of the clinical and genetic findings.

Prostaglandin-endoperoxide synthase genes COX1 and COX2 - novel modifiers of disease severity in cystic fibrosis patients.

Cystic fibrosis (CF) is one of the most common autosomal recessive diseases among Caucasians caused by a mutation in the CFTR gene. However, the clinical outcome of CF pulmonary disease varies remarkably even in patients with the same CFTR genotype. This has led to a search for genetic modifiers located outside the CFTR gene. The aim of this study was to evaluate the effect of functional variants in prostaglandin-endoperoxide synthase genes (COX1 and COX2) on the severity of lung disease in CF patients. To the best of our knowledge, it is the first time when analysis of COX1 and COX2 as potential CF modifiers is provided. The study included 94 CF patients homozygous for F508del mutation of CFTR. To compare their clinical condition, several parameters were recorded, e.g. a unique clinical score: disease severity status (DSS). To analyse the effect of non-CFTR genetic polymorphisms on the clinical course of CF patients, the whole coding region of COX1 and selected COX2 polymorphisms were analysed. Statistical analysis of genotype-phenotype associations revealed a relationship between the heterozygosity status of identified polymorphisms and better lung function. These results mainly concern COX2 polymorphisms: -765G>C and 8473T>C. The COX1 and COX2 polymorphisms reducing COX protein levels had a positive effect on all analysed clinical parameters. This suggests an important role of these genes as protective modifiers of pulmonary disease in CF patients, due to inhibition of arachidonic acid conversion into prostaglandins, which probably reduces the inflammatory process.

Loss of heterozygosity on chromosomes 2p, 3p, 18q21.3 and 11p15.5 as a poor prognostic factor in stage II and III (FIGO) cervical cancer treated by radiotherapy.

Loss of heterozygosity (LOH) has been shown to be an important prognostic factor in a variety of malignant neoplasm's. Cervical cancer develops as result of multiple genetic alterations. The aim of this study was to analyze presence of LOH in cervical cancer and to identify the correlation between LOH and survival and relapse-free survival time in patients treated with radiotherapy. Studies were performed on tumor specimens and venous blood from 20 patients with cervical cancer (squamous cell carcinoma G2 and G3) in stage II and III (FIGO) treated with radiotherapy. DNA was isolated using organic extraction. Additional microcolumn purification was performed. The fluorescent multiplex polymerase chain reaction (PCR) was used to amplify 10 microsatellite loci included in commercially available human identification kits. Microsatellite marker BAT 26 was amplified in separate PCR reactions. 75% cervical cancers manifested LOH. LOH in BAT 26 analysis (chromosome 2) was present in all these specimens. 60% of the cases showed LOH at one or more of other examined loci (mostly on 3p, 18q21.3, and 11p15.5). Eight of nine cervical cancers in clinical stage III showed LOH. All cases of G3 squamous cell carcinoma of the cervix manifested LOH on 2p. Patients with LOH have worse prognosis for survival and relapse-free survival compared to patients without LOH.

1H NMR conformational study of a variety of alpha-anomers of C5-substituted 2'-deoxyuridines: comparison to their antiherpetic beta counterparts.

Although alpha-nucleosides are not found in nucleic acid, they do occur as constituents of smaller molecules in living cells, e.g., in vitamin B(12). There are now several examples of alpha-nucleosides exerting a biological activity in some instances equal to, or even exceeding, that of the corresponding beta-anomer. Examples include growth inhibitory properties against mouse leukemia cells and antitumor activity. From stereochemical point of view, alpha-anomers serve as references for studying of interaction of the base with the sugar moiety in beta-anomers and may help in better understanding of structure-activity relationships. One important problem preventing conformational analysis of alpha nucleosides is uncertainty in the determination of vicinal coupling constants from simulation of overlapping sugar proton resonances of strongly coupled spin systems. A successful resolution of near-isochronous H3' and H4' resonances made possible a full conformational analysis for a series of alpha-anomers C5-substituted 2'-deoxyuridines, including methyl, ethyl, isopropyl, fluor, vinyl, and bromovinyl, in comparison to their beta counterparts. Conformation of the sugar ring is determined from proton-proton coupling constants and described in terms of pseudorotation between two main puckering domains C2'endo (S) and C3'endo (N). A thorough analysis of chemical shifts as well as conformation of the sugar ring and C4'-C5' rotamers made possible determination of conformational preferences in equilibrium about the glycosidic bond between two regions, anti and syn. This work provides insights into the role of anomeric configuration of the base in conformational behavior of the sugar moiety, a link in the backbone of nucleic acids.

[Changes of serum il-6 and CRP after chemotherapy in patients with ovarian carcinoma]. / Zmiany stezenia IL-6 i CRP w surowicy chorych na nablonkowe nowotwory jajnika po leczeniu cytostatycznym.

The levels of IL-6, CRP and TPS were measured in 38 patients with ovarian carcinoma in different histological types and clinical stages. The values IL-6, CRP and TPS were determined before and after chemotherapy. Pretreatment levels of IL-6, CRP and TPS were significantly increased in carcinoma patients relatively to the control group. The frequency of increased results and absolute value of IL-6 and TPS levels showed tendency to significant increase with the stage of disease. The highest values of IL-6 were observed in patients with serous and mucous carcinoma. The levels of IL-6, CRP and TPS were decreased above cut off values in patients with remission, and did not changed in patients with progression and stabilization disease. The results suggest that IL-6 especially in the combination with CRP and TPS may be useful in the diagnosis and the evaluation of therapy of patients with ovarian carcinoma.

5-Substituted N(4)-hydroxy-2'-deoxycytidines and their 5'-monophosphates: synthesis, conformation, interaction with tumor thymidylate synthase, and in vitro antitumor activity.

Convenient procedures are described for the synthesis of 5-substituted N(4)-hydroxy-2'-deoxycytidines 5a,b,d-h via transformation of the respective 5-substituted 3', 5'-di-O-acetyl-2'-deoxyuridines 1a-c,e-h. These procedures involved site-specific triazolation or N-methylimidazolation at position C(4), followed by hydroxylamination and deblocking with MeOH-NH(3). Nucleosides 5a,b,d-h were selectively converted to the corresponding 5'-monophosphates 6a,b,d-h with the aid of the wheat shoot phosphotransferase system. Conformation of each nucleoside in D(2)O solution, deduced from (1)H NMR spectra and confirmed by molecular mechanics calculations, showed the pentose ring to exist predominantly in the conformation S (C-2'-endo) and the N(4)-OH group as the cis rotamer. Cell growth inhibition was studied with two L5178Y murine leukemia cell lines, parental and 5-fluoro-2'-deoxyuridine (FdUrd)-resistant, the latter 70-fold less sensitive toward FdUrd than the former. With FdUrd-resistant L5178Y cells, 5-fluoro-N(4)-hydroxy-2'-deoxycytidine (5e) caused almost 3-fold stronger growth inhibition than FdUrd; 5e was only some 3-fold weaker growth inhibitor of the resistant cells than of the parental cells. Thymidylate synthase inhibition was studied with two forms of the enzyme differing in sensitivities toward 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP), isolated from parental and FdUrd-resistant L1210 cell lines. All N(4)-hydroxy-dCMP (6a,b,d-h) and dUMP analogues studied were competitive vs dUMP inhibitors of the enzyme. Analogues 6b,d-h and 5-hydroxymethyl-dUMP, similar to N(4)-hydroxy-dCMP (6a) and FdUMP, were also N(5), N(10)-methylenetetrahydrofolate-dependent, hence mechanism-based, slow-binding inhibitors. 5-Chloro-dUMP, 5-bromo-dUMP, and 5-iodo-dUMP, similar to dTMP, did not cause a time-dependent inactivation of the enzyme. Instead, they behaved as classic inhibitors of tritium release from [5-(3)H]dUMP. 5-Bromo-dUMP and 5-iodo-dUMP showed substrate activity independent of N(5), N(10)-methylenetetrahydrofolate in the thymidylate synthase-catalyzed dehalogenation reaction. The =N-OH substituent of the pyrimidine C(4) prevented the enzyme-catalyzed release from the C(5) of Br(-) and I(-) (the same shown previously for H(+)). While FdUMP and 6a showed a higher affinity and greater inactivation power with the parental cell than FdUrd-resistant cell enzyme, an opposite relationship could be seen with 5-hydroxymethyl-dUMP.

Spectroscopic detection of photoproducts in lecithin model system after 8-methoxypsoralen plus UV-A treatment.

Photoreactions of 8-methoxypsoralen (8-MOP) in the presence of synthetic lecithins esterified at the beta-position with linoleic/oleic and gamma-palmitic acid (PCd2/d1pal) have been studied. Following UV-A (320-400 nm) irradiation, the photoproducts separated by thin-layer chromatography are analysed by UV absorption spectroscopy, nuclear magnetic resonance and mass spectroscopy. The new isolated products are lecithin double cyclobutane adducts, PC-(8-MOP)2, fatty acid-8-MOP split adducts from phosphatidylcholine and lecithin adducts with photo-oxidized 8-MOP. The photolysis performed in the presence of 8-MOP is related to the previously reported lecithin cyclobutane adducts with psoralen. A hypothetical scheme of lecithin photolysis under PUVA (psoralen + UV-A) treatment is proposed. We suggest that photolysis of lecithin may have a significant role in the chain of reactions triggered in cell membrane submitted to PUVA treatment.

1H NMR conformational study of antiherpetic C5-substituted 2'-deoxyuridines: insight into the nature of structure-activity relationships.

1H NMR study and conformational analysis of a broad series of biologically important C5-substituted 2'-deoxyuridines, including alkyl, halogen, vinyl, hydroxymethyl, and hydroxy derivatives as well as nitro, formyl, trifluoromethyl, and dimethylamino substituents, is presented. A thorough analysis of chemical shifts in correlation with C5-substituent electronegativity as well as calculations by SCF semi-empirical method of the formal charge localized on C6 carbon is discussed in terms of charge distribution for electron attracting and electron donating groups. Conformation of the sugar ring is determined from proton-proton coupling constants and described in terms of pseudorotation between two main puckering domains C2'endo (S) and C3'endo (N). Generally, electron donating groups destabilise the N conformation, simultaneously decreasing the mean pseudorotation amplitude. Absolute assignments of the H5' and H5'' methylene protons in 1H NMR spectra permitted the unequivocal determination of molar fractions of the three classical exocyclic C4'-C5' rotamers gauche+, trans, and gauche-, and correlation of them with the sugar ring puckering domains. Conformation about the glycosidic bond is described in terms of equilibrium between two conformational regions, anti and syn. Finally, the role of the C5-substituent in the creation of cytotoxic activity is considered on the basis of a simplified model assuming that compound activity is a function of substituent polar surface, its molecular volume, and its molecule polarity defined at the relative partition of the polar atoms.

Solution structure of a lipid transfer protein extracted from rice seeds. Comparison with homologous proteins.

Nuclear magnetic resonance (NMR) spectroscopy was used to determine the three dimensional structure of rice nonspecific lipid transfer protein (ns-LTP), a 91 amino acid residue protein belonging to the broad family of plant ns-LTP. Sequence specific assignment was obtained for all but three HN backbone 1H resonances and for more than 95% of the 1H side-chain resonances using a combination of 1H 2D NOESY; TOCSY and COSY experiments at 293 K. The structure was calculated on the basis of four disulfide bridge restraints, 1259 distance constraints derived from 1H-1H Overhauser effects, 72 phi angle restraints and 32 hydrogen-bond restraints. The final solution structure involves four helices (H1: Cys3-Arg18, H2: Ala25-Ala37, H3: Thr41-Ala54 and H4: Ala66-Cys73) followed by a long C-terminal tail (T) with no observable regular structure. N-capping residues (Thr2, Ser24, Thr40), whose side-chain oxygen atoms are involved in hydrogen bonds with i + 3 amide proton additionally stabilize the N termini of the first three helices. The fourth helix involving Pro residues display a mixture of alpha and 3(10) conformation. The rms deviation of 14 final structures with respect to the average structure is 1.14 +/- 0.16 A for all heavy atoms (C, N, O and S) and 0.72 +/- 0.01 A for the backbone atoms. The global fold of rice ns-LTP is close to the previously published structures of wheat, barley and maize ns-LTPs exhibiting nearly identical pattern of the numerous sequence specific interactions. As reported previously for different four-helix topology proteins, hydrophobic, hydrogen bonding and electrostatic mechanisms of fold stabilization were found for the rice ns-LTP. The sequential alignment of 36 ns-LTP primary structures strongly suggests that there is a uniform pattern of specific long-range interactions (in terms of sequence), which stabilize the fold of all plant ns-LTPs.

Significance of some tumor markers in differential diagnosis of ovarian tumor.

The levels of CA-125, CA 72-4 and CEA were evaluated in serum of patients with various histological types and clinical stages of ovarian carcinoma and of benign ovarian tumor. An increased CA-125 was found in 8% patients with benign ovarian tumor. The antigens CA 72-4 and CEA exhibit values below the cut-off limit. CA-125 value was significantly elevated in patients with serous and CA 72-4 with ovarian mucinous carcinoma. An increase of CA-125 was found in 81% of patients with serous, 60% with endometrioid and 30% with ovarian mucinous carcinoma. An increase of CA 72-4 was found in 76% of patients with mucinous, 54% with serous and 45% with ovarian endometrioid carcinoma. Insignificant rise of CEA value was found in 8% of patients with serous, 10% with endometrioid and 15% with ovarian mucinous carcinoma. The frequency of increased concentration of antigens level showed a trend to significant increase and a correlation with the clinical stage of disease. The observations allow to conclude that the determination of CA 72-4 in the serum may be useful in differentiation diagnostics of benign and malignant ovarian tumors. The combined determination of CA-125 and CA 72-4 is useful in differentiation of histological types of ovarian tumors and their clinical stage.

Pulse radiolysis studies of intramolecular electron transfer in model peptides and proteins. 7. Trp-->TyrO radical transformation in hen egg-white lysozyme. Effects of pH, temperature, Trp62 oxidation and inhibitor binding.

Intramolecular long-range electron transfer (LRET) in hen egg-white lysozyme (HEWL) accompanying Trp-->TyrO radical transformation was investigated in aqueous solution by pulse radiolysis as a function of pH (5.2-7.4) and temperature (283-328 K). The reaction was induced by highly selective oxidation of Trp with N3 radicals under low concentration of the reactants but at a high HEWL/N3 molar ratio, so that more than 99% of the oxidized protein molecules contained only a single tryptophyl radical. Synchronous decay of Trp and build-up of TyrO conformed satisfactorily to first-order kinetics, indicating that LRET involved either one or more Trp./Tyr redox pairs characterized by similar rate constants. The rate constant of LRET, k5, increased monotonously with decreasing pH showing the following characteristics: (i) in the pH range 7.4-5.2 the plot of k5 against pH was sigmoidal in shape, reflecting protonation of Glu35 (pKa approximately 6) and pointing to involvement of conformational control of the kinetics of LRET, (ii) below pH 5.2 a sharp increase in k5 was observed due to the protonation of Trp to form TrpH.+, which is known to oxidize tyrosine faster than does Trp.. Arrhenius plots of the temperature-dependence of k5 showed that the activation energy of LRET varies both with temperature and the protonation state of the enzyme. The activation energies are in the range 7.6-56.0 kJ mol-1, and are similar to those for activation of amide hydrogen exchange in native HEWL below its denaturation temperature. Selective oxidation by ozone of the Trp62 indole side-chain in HEWL to N'-formylkynurenine (NFKyn62-HEWL) caused a large drop in the initial yield of Trp. radicals, G(Trp.)i. This was accompanied by a relatively small decrease in k5 but selective oxidation by ozone had a pronounced effect on its temperature-dependence. Taken together these observations indicate that of the six tryptophans present in HEWL Trp62 contributes about 50% to the yield of the observed LRET. In the enzyme-inhibitor complex, HEWL(GlcNAc)3, where Trp62 and Trp63 are completely shielded from the solvent by the bound triacetylchitotriose, G(Trp.)i was lower than in NFKyn62-HEWL, and both the kinetic and energetic characteristics of LRET, observed at pH 5.2, were again somewhat different than in HEWL alone. Considering known solvent accessibilities of tryptophans in the complex, the observed LRET process in HEWL(GlcNAc)3 was assigned to Trp123. Theoretical evaluation of the electronic coupling for the dominant LRET pathways between all the potential Trp/Tyr redox couples in HEWL, with help of the PATHWAYS model, enabled Trp623/Tyr53, Trp63/Tyr53 and Trp123/Tyr23 to be identified as the pairs involved in the experimentally observed electron transfer.

Synthesis and interactions with thymidylate synthase of 2,4-dithio analogues of dUMP and 5-fluoro-dUMP.

The 2,4-dithio analogues of 2'-deoxyuridine and 2'-deoxy-5-fluorouridine have been synthesized by thiation of the previously described 2-thio analogues, and then phosphorylated enzymatically or chemically to yield 2,4-dithio-dUMP and 2,4-dithio-5-fluoro-dUMP. In striking contrast to the 2-thio and 4-thio analogues of dUMP, which are good substrates of thymidylate synthase, 2,4-dithio-dUMP is not a substrate. But, surprisingly, it is a competitive inhibitor, relative to dUMP, of the purified enzymes from both parental and FdUrd-resistant L1210 cells, with K(i) values of 32 microM and 55 microM, respectively. Although 2,4-dithio-5-fluoro-dUMP behaved as a typical slow-binding inhibitor of the enzyme, its K(i) value was 10(3)-10(4)-fold higher than those for the corresponding 2-thio and 4-thio congeners. Similarly, 2,4-dithio-FdUrd was a much weaker inhibitor of tumour cell growth (IC50 approximately 10(-5)M) than FdUrd (IC50 approximately 10(-9)M), 2-thio-FdUrd(IC50 approximately 10(-7)M) or 4-thio-FdUrd (IC50 approximately 5x10(-8)M), while with 2,4-dithio-dUrd no influence on cell growth could be observed. Theoretical considerations, based on calculated aromaticities of the uracil and thiouracil rings, suggest that lack of substrate activity of 2,4-dithio-dUMP may result from increased pyrimidine ring aromaticity of the latter, leading to resistance of C(6) to nucleophilic attack by the enzyme active center cysteine.

[Tumor of a single functional kidney treated with selective embolization]. / Guz jedynej czynnej nerki leczony selektywna embolizacja.

Occurrence malignant tumor in only one functional kidney (second one was small and cirrhotic with a large cyst) and potentiality of treatment with selective embolization of renal artery were cause of that report. Patient achieved a long and comfortable term of survival (without any troubles). We suggest that method is useful and safe for such cases.

CD investigations on conformation of H-X-(Pro)n-Y-OH peptides (X = Trp, Tyr; Y = Tyr, Met); models for intramolecular long range electron transfer.

Conformations of three series of peptides: H-Trp-(Pro)n-Tyr-OH (n = 1-5), H-Trp-(Pro)n-Met-OH (n = 1-3) and H-Tyr-(Pro)n-Met-OH (n = 1-3), used as models in studies on long range electron transfer through protein matrix, were investigated by CD spectroscopy in aqueous solution at pH 5.2 in the temperature range of 10 degrees C-90 degrees C. CD spectra of their component N- and C-terminal dipeptide and oligoproline fragments were also measured under similar conditions. In interpretation of the spectra the cis<-->trans equilibrium about X-Pro bonds was taken into account and CD spectra of Trp-Pro and Tyr-Pro chromophores in trans and cis configuration of the peptide bond were evaluated. The spectra of n = 3-5 peptides from the first series and those with n = 2-3 from the other two series exhibit a strong negative band in the 202-207 nm region, the strength of which is proportional to the number of Pro residues in the (Pro)n bridge, and characterized by a large temperature decrement. In view of close similarity between characteristics of this band and the 206 nm band of aqueous oligoproline peptides (n > or = 3), known to attain a left handed helical conformation similar to that of 3(1) helix of the all-trans poly-L-proline II, this band was attributed to a conformation of the latter type. H-Trp-(Pro)2-Tyr-OH does not form this conformation due to sterical interaction between the two bulky aromatic side chains. Conclusions drawn from analysis of the CD spectra are supported by 1H and 13CNMR data reported elsewhere.

1H- and 13C-NMR investigations on cis-trans isomerization of proline peptide bonds and conformation of aromatic side chains in H-Trp-(Pro)n-Tyr-OH peptides.

1H and 13C high-resolution nmr spectra of cationic, zwitterionic, and anionic forms of the peptides: H-Trp-(Pro)n-Tyr-OH, n = 0-5, and H-Trp-Pro-OCH3 were obtained in D2O solution. Analysis of H alpha (Pro1), H alpha (Trp), C gamma (Pro), H epsilon (Tyr), and H delta (Trp) resonances provided evidence for the presence of two predominant backbone isomers: the all-trans one and another with the Trp-Pro peptide bond in cis conformation; the latter constituted about 0.8 molar fraction of the total peptide (n > 1) concentration. Relative content of these isomers varied in a characteristic way with the number of Pro residues and the ionization state of the peptides. The highest content of the cis (Trp-Pro) isomer, 0.74, was found in the anionic form of H-Trp-Pro-Tyr-OH; it decreased in the order of: anion >> zwitterion approximately cation, and with the number of Pro residues to reach the value of 0.42 in the cationic form of H-Trp-(Pro)5-Tyr-OH. Isomerization equilibria about Pro-Pro bond(s) were found to be shifted far (> or = 0.9) in favor of the trans conformation. Interpretation of the measured vicinal coupling constants J alpha-beta' and J alpha-beta" for C alpha H-C beta H2 proton systems of Trp and Tyr side chains in terms of relative populations of g+, g-, and t staggered rotamers around the chi 1 dihedral angle indicated that in all the peptides studied (a) rotation of Trp indole ring in cis (Trp-Pro) isomers is strongly restricted, and (b) rotation of Tyr phenol ring is relatively free. The most preferred chi 1 rotamer of Trp (0.8-0.9 molar fraction) was assigned as the t one on the basis of a large value of the vicinal coupling constant between the high-field H beta and carbonyl carbon atoms of Trp, estimated for the cis (Pro1) form of H-Trp-Pro-Tyr-OH from a 1H, 13C correlated spectroscopy 1H-detected multiple quantum experiment. This indicates that cis<-->trans equilibrium in the Trp-Pro fragment is governed by nonbonding interactions between the pyrrolidine (Pro) and indole (Trp) rings. A molecular model of the terminal cis Trp-Pro dipeptide fragment is proposed, based on the presented nmr data and the results of our molecular mechanics modeling of low-energy conformers of the peptides, reported elsewhere.

[Metastasis of penile cancer to the heart in a 20-year-old patient]. / Przerzut raka pracia do serca u 20-letniego chorego.

A case of penile cancer was observed in a 20-year-old patient with very extensive remote metastases. On autopsy metastases were found to the heart and brain which are exceptionally rare in penile cancer.

Bioelectrorheological model of the cell. 3. Viscoelastic shear deformation of the membrane.

An analytical electromechanical model of a spherical cell exposed to an alternating electric field was used to calculate shear stress generated in the cellular membrane. Shape deformation of Neurospora crassa (slime) spheroplasts was measured. Statistical analysis permitted empirical evaluation of creep of the cellular membrane within the range of infinitesimal stress. Final results were discussed in terms of various rheological models.