Empirical rules predicting conformation of cyclic tetrapeptides from primary structure

A useful set of empirical rules is put forward to predict the conformations of cyclic tetrapeptides and cyclic tetradepsipeptides on the basis of primary structure, briefly presented as follows: 1. A conformation allowing an intramolecular hydrogen bond (IMHB) of γ-turn is preferred, and an ester bond always adopts a trans form. 2. On a right-handed peptide ring, the carbonyl group acylating a D residue is oriented to the upper side of the main ring. 3. The carbonyl group acylating a d proline or an N-methyl-d -amino acid residue is oriented to the lower side of the ring, forming a cis bond. 4. The lddl configurational sequence adopts a cis-trans-cis-trans backbone with C_i symmetry. 5. A glycine residue behaves as a d residue in an l -peptide. Conformations of cyclotetrapeptides containing two glycine residues at diametric positions or containing an N-methyl-dehydroamino acid residue are predicted by use of appendices of rule 5. Almost all conformations of cyclic tetrapeptides are predicted by these rules. Energetical rationalization of the rules and prediction of possible new conformations are described. Conformations of cyclo (-l -Pro-l -Leu-d -Tyr(Me)-l -Ile-)(1) and cyclo (-l -Pro-d -Leu-d -Tyr(Me)-l -Ile)(2) are compared. Results of n.m.r. experiments showed that compound 1 adopts a unique cis-trans-trans-trans backbone with a γ-turn IMHB, and 2 has a cis-trans-cis-trans backbone with C_i symmetry. These observations confirmed the rules described above. Peptides 1 and 2 are the first diastereomeric peptides with trans (ld ) and cis (dd ) secondary amide bonds.     

Expression of urokinase-type plasminogen activator receptor and plasminogen activator inhibitor-1 in gastric cancer

In gastric cancer, the urokinase-type plasminogen activator (uPA) system plays important roles in invasion and metastasis, processes which entail proteolysis and adhesion. Both the urokinasetype plasminogen activator receptor (uPAR) and the plasminogen activator inhibitor-1 (PAI-1) are thought to be important factors in this system. To clarify the relationship between these two factors and gastric cancer invasiveness, we evaluated the expression of uPAR and PAI-1 in 91 cases of gastric cancer by immunohistochemistry and in situ hybridization. Urokinase-type plasminogen activator receptor-mRNA, PAI-1-mRNA, uPAR and PAI-1 protein were diffusely distributed in the cytoplasm of the cancer cells and concentrated at invasive foci. Urokinase-type plasminogen activator receptor protein expression correlated with lymphatic, venous invasion (P<.01) and lymph node metastasis (P<0.05); uPAR-mRNA expression correlated with lymphatic, venous invasion and lymph node metastasis (P<0.05). Plasminogen activator inhibitor-1 protein expression correlated with lymphatic, venous invasion, lymph node metastasis and depth of invasion (P<0.01); PAI-1-mRNA expression was linked to lymphatic, venous invasion (P<0.01), lymph node metastasis and depth of invasion (P<0.05). This suggests that the proteolytic activity of uPAR and the cellular motility of PAI-1 in gastric cancer cells may determine penetration of lymphatic and blood vessels, whereby lymph node metastasis may be promoted and that the promotion of cellular motility by PAI-1 may influence the depth of cancer invasion.     

Case Report: Hepatic adenoma with bone marrow metaplasia in a patient with glycogen storage disease type 1a

A 34 year old man with glycogen storage disease type 1a had two hepatic tumours since 18 years of age. They had continued to grow until he was 24 years old, but showed no further growth since then. He underwent a right hepatic trisegmentectomy with caudate lobectomy under veno-venous bypass. The tumour in the posterior segment showed nodule-within-nodule appearance. Histologically, the inner adenoma with dysplasia, bone marrow metaplasia and lymphocytic infiltration was separated by a fibrous band from the outer adenoma of usual histology.     

Proarrhythmic ECG Deterioration Caused by Myocardial Ischemia of the Conus Branch Artery in Patients with a Brugada ECG Pattern

The Brugada‐type electrocardiogram (ECG) is characterized by ST‐segment elevation in the right precordial ECG leads and has been reported to have the potential of sudden death. Right ventricular outflow tract supplied from the conus branch of the coronary artery (CB) is considered as the anatomopathologic substrate of Brugada syndrome. We experienced two asymptomatic patients with a saddleback Brugada‐type ECG who exhibited a dynamic ECG conversion to a coved type following a ventricular fibrillation/ventricular tachycardia (VT/VF) episode when myocardial ischemia occurred exclusively at the CB. Some types of Brugada syndrome might be caused VT/VF by selective myocardial ischemia at the CB. (PACE 2011; 34:e26–e29)