Portopulmonary hypertension and the risk of high right ventricular systolic pressure in liver transplant candidates.

AIM: Portopulmonary hypertension (PoPH) is a rare and serious complication of liver cirrhosis and portal hypertension that can interfere with liver transplantation (LT). We evaluated the prevalence of PoPH and the clinical features of right ventricular systolic pressure (RVSP), which is equivalent to pulmonary artery systolic pressure, in LT candidates. METHODS: This was a single-center retrospective study. A total of 157 Japanese patients with decompensated liver cirrhosis or portal hypertension (76 men, median age = 52 years [range: 18-68 years]) were enrolled. The relationships between RVSP and clinical parameters, and the prevalence of PoPH in LT candidates, were evaluated. RESULTS: The cardiological parameters were as follows: brain natriuretic peptide (BNP), 39.1 (4.0-780.5) pg/mL; RVSP, 31.2 (16.0-122.4) mmHg; ejection fraction, 58% (28-72%); and mean peak tricuspid regurgitation velocity, 2.3 (1.5-5.3) m/s. The RVSP was significantly higher in females (p = 0.02) and primary biliary cholangitis (PBC) patients (p = 0.01), and was weakly correlated with the BNP level (r = 0.40, p = 0.01). For RVSPs of < 36 and ≥ 36 mmHg, the 5-year survival rates were 36.1% versus 34.1%, and 85.4% versus 85.3%, in non-LT and LT cases, respectively (p = 0.47 and 0.69, respectively). Among six patients with an RVSP ≥ 50 mmHg, three (1.9%) were diagnosed with PoPH and treated with vasodilators. CONCLUSIONS: PoPH was observed in 3 cases (1.9%) in 157 LT candidates. In patients with suspected mild pulmonary hypertension (RVSP, 36 - 50 mmHg), LT was successfully performed.

Young gastric cancer patient with high CA19-9 complicated by Trousseau syndrome.

A 47-year-old Japanese woman presented with epigastric discomfort and anorexia. Upper endoscopy showed type 4 advanced gastric cancer in the gastric antrum with stenosis of the pyloric portion. Abdominopelvic CT revealed peritoneal dissemination, and stage IV advanced gastric cancer was diagnosed. Laparoscopic gastrojejunostomy and enterostomy were performed. Trousseau syndrome occurred 7 days post-surgery. Despite appropriate treatment, the patient developed a pulmonary embolism 13 days later and died 18 days post-surgery. Even in young cancer patients without lifestyle disease complications, it is important to pay attention to Trousseau syndrome as part of cancer management.

Structure-activity relationship study of a CXC chemokine receptor type 4 antagonist, FC131, using a series of alkene dipeptide isosteres.

A structure-activity relationship study on a highly potent CXC chemokine receptor type 4 (CXCR4) antagonist, FC131 [cyclo(-d-Tyr(1)-Arg(2)-Arg(3)-Nal(4)-Gly(5)-)], was carried out using a series of alkene isosteres of the d-Tyr(1)-l/d-Arg(2) dipeptide to investigate the binding mode of FC131 and its derivatives with CXCR4. The structure-activity relationships of isostere-containing FC131 analogues were similar to those of the parent FC131 and its derivatives, suggesting that a trans-conformer of the d-Tyr(1)-Arg(2) peptide bond is the dominant contributor to the bioactive conformations of FC131. Although NMR analysis demonstrated that the two conformations of the peptidomimetic containing the d-Tyr(1)-d-Arg(2) isostere are possible, binding-mode prediction indicated that the orientations of the alkene motif within d-Tyr(1)-MeArg(2) peptidomimetics depend on the chirality of Arg(2) and the ß-methyl group of the isostere unit, which makes the dominant contribution for binding to the receptor. The most potent FC122 [cyclo(-d-Tyr(1)-d-MeArg(2)-Arg(3)-Nal(4)-Gly(5)-)] bound with CXCR4 by a binding mode different from that of FC131.

Synthesis and biological evaluation of selective CXCR4 antagonists containing alkene dipeptide isosteres.

A set of cyclic peptide analogues of a selective CXCR4 antagonist FC131 [cyclo(-d-Tyr-Arg-Arg-Nal-Gly-)] were synthesized and bioevaluated. Using (E)-alkene and (Z)-fluoroalkene dipeptide isosteres for Arg-Arg and Arg-Nal substructures, indispensable or the partial contribution of the two peptide bonds to the CXCR4 antagonism and anti-HIV activity was demonstrated. FC131 and the analogues were shown to selectively inhibit SDF-1 binding to CXCR4, whereas no inhibition of binding of SDF-1 to CXCR7 was observed.

Highly beta-selective C-allylation of a ribofuranoside controlling steric hindrance in the transition state.

A highly beta-selective C-allylation of 2,3-O-(3-pentylidene)-D-ribofuranosyl fluoride is described. This strategy will provide a new concept for synthesizing beta-C-ribosides by controlling the effect of steric hindrance in the transition state.

Past history of obesity (overweight by WHO criteria) is associated with an increased risk of nonfatal acute myocardial infarction: a case-control study in Japan.

BACKGROUND: Obesity is an important risk factor for the occurrence of coronary artery disease (CAD) in Western countries and furthermore, it often coexists with other CAD risk factors such as hypertension, dyslipidemia and diabetes mellitus. However, it is uncertain whether obesity is a CAD risk factor in Japan because Japanese are relatively thin on average. METHODS AND RESULTS: The CAD risk associated with obesity (body mass index > or =25.0) 10 years before as well as at the time of the survey was assessed in a case - control study of acute myocardial infarction (AMI), which compared 660 AMI patients aged 40-79 years and 1,277 community controls, matched to each case by sex, year of birth, and residence. The prevalence of current obesity did not show any material difference between cases and controls, but compared with controls, past obesity was much more frequent in cases. Even after controlling for other CAD risk factors, past obesity was associated with a 2-fold increase in the risk of AMI. Past obesity was associated with an increased risk of AMI even without current obesity. CONCLUSION: Past obesity is a CAD risk, even after weight reduction.

The medaka fish Tol2 transposable element can undergo excision in human and mouse cells.

Tol2 is an active DNA-based transposable element identified in the medaka fish, Oryzias latipes. Originating from a vertebrate and belonging to the hAT ( hobo/ Activator/ Tam3) transposable element family, featuring a wide distribution among organisms, Tol2 would be expected to be active if introduced into mammals. We, therefore, examined if excision, one part of the transposition reaction, can occur in human and mouse culture cells. A Tol2 clone was introduced into cells and, after incubation, recovered. PCR and sequencing analysis provided evidence for precise and near precise excision in these cells. Tol2 can thus be expected to serve as a material for developing a gene transfer vector and other genetic tools applicable to mammals. It was also suggested that an intact Tol2 element could retain autonomy as a transposable element in mammalian cells.

Assessing cerebral representations of short and long vowel categories by NIRS.

The present study examined cerebral representations of Japanese long and short vowel categories with near-infrared spectroscopy (NIRS) by measuring the hemodynamic changes. Results showed that NIRS could capture phoneme-specific information. The left side of the auditory area showed large hemodynamic changes only for contrasting stimuli between which the phonemic boundary was estimated, but not for stimuli differing by an equal duration but belonging to the same phoneme category. Left dominance in phoneme processing was also confirmed for the across-category stimuli. These findings indicate that the Japanese vowel contrast based only on duration differences is dealt with in the same language-dominant hemisphere as other spectrally varying phonemic categories, and that the cortical activities related to its processing can be detected with NIRS.