[Hepatic echinococcosis that required 11 years for a definitive diagnosis: a case report].

A woman in her 80s underwent computed tomography that revealed a 22-mm-sized unilocular mass in segment 4 of her liver. The mass grew to 26mm at the 4-year follow-up and to 36mm at the 11-year follow-up, becoming a multilocular mass that invaded the bile duct. At this point, the patient was diagnosed with hepatic echinococcosis based on a serological examination and oral albendazole treatment was initiated. The patient developed cholangitis and underwent endoscopic biliary stenting 12 years after her initial diagnosis. We consider this case valuable as it allowed us to follow the natural course of hepatic echinococcosis.

[A case of systemic amyloidosis presenting with gastric emphysema].

The patient was an elderly woman in her 80s. Upper and lower gastrointestinal endoscopies were conducted as a thorough analysis for cardiac amyloidosis, revealing no abnormal findings. A mucosal biopsy, however, resulted in an amyloid AA-type amyloidosis diagnosis. About 2 months later, she visited our department with sudden vomiting and epigastric pain onset. Plain abdominal radiography and computed tomography demonstrated gastric emphysema, and thus, she was admitted to our department. The gastric emphysema was alleviated with conservative treatment. Herein, we report a valuable case in which gastric emphysema manifested as a gastrointestinal tract lesion of amyloidosis.

Pleural Invasion Depth of Disseminated Nodules in Patients with Stage IVa or Recurrent Thymoma: Assessment, Curative Impact, and Surgical Outcomes.

BACKGROUND: Thymoma patients with pleural dissemination are difficult to manage, and their treatment strategy remains undefined. This study aimed to investigate the clinicopathologic features of these patients, focusing on the association between the depth of pleural invasion and prognosis. METHODS: Between 2003 and 2019, the study identified 120 disseminated lesions in 20 thymoma patients. Seven patients had de novo stage IVa thymoma and 13 were recurrent cases. Extrapleural pneumonectomy was performed for 8 patients and debulking surgery for 12 patients. Invasion depth of pleural tumors was classified into two groups: when the disseminated tumors invaded the pleura beneath the elastic layer, the tumor was diagnosed as Da, and when the disseminated tumors invaded the pleura beyond the elastic layer, the tumor was diagnosed as Db. RESULTS: Of 120 nodules, 31 (26%), found in eight patients with recurrent malignancies, were classified as Db. The pathologic status of the surgical margin (PSM) was positive in eight patients, seven of whom had Db nodules. The 5-year overall survival (OS) rate was 100% in the Da group and 75% in the Db group (P = 0.02). The 5-year progression-free survival (PFS) rate was 66.7% in the Da group and 25% in the Db group (P = 0.02). Cox univariate analysis showed that PFS was significantly influenced by the depth of invasion (P = 0.04) and PSM (P = 0.03). CONCLUSION: Depth of pleural invasion may influence survival outcomes for thymoma patients with pleural dissemination. The patients in this study with Da-disseminated nodules had an increased probability of a longer OS and PFS and tended to achieve negative PSM compared with the patients with Db.

Risk Assessment for Loss-of-Exercise Capacity After Lung Cancer Surgery: Current Advances in Surgery and Systemic Treatment.

BACKGROUND: Considering advances in current post-recurrence treatment, we examined the prognostic significance of the number of risk factors for loss-of-exercise capacity (LEC) after lung cancer surgery, which were identified by our previous prospective observational study. METHODS: Risk factors for LEC were defined as a short baseline 6-min walk distance (<400 m), older age (≥75 years), and low predicted postoperative diffusing capacity for carbon monoxide (<60%). Patients were classified as Risk 0/I/II/III according to the number of risk factors. The survival data were retrospectively analyzed. RESULTS: Between 2014 and 2017, 564 patients (n = 307, 193, 57, 7; Risk 0/I/II/III) who underwent lung cancer surgery were included in the study. The number of risk factors was associated with smoking status, predicted postoperative forced expiratory volume in 1 s, histology, pathological stage, and adjuvant therapy. In a multivariate Cox regression analysis, compared to Risk 0, Risk I/II/III showed significant associations with overall survival (hazard ratios: 1.92, 3.35, 9.21; 95% confidence interval: 1.27-2.92, 2.01-5.58, 3.64-23.35; Risk I/II/III, respectively). In 141 patients with recurrence, molecular targeted therapies (MTTs) or immune checkpoint inhibitors (ICIs) were included in 58%, 47%, 32%, and 0% (Risk 0/I/II/III) during the course of treatment. In patients with MTT/ICI treatment, the estimated 1-year and 3-year post-recurrence survival rates were 88% and 58%, respectively. CONCLUSIONS: Risk classification for LEC was associated with survival after lung cancer surgery, as well as post-recurrence treatment. The concept of physical performance-preserving surgery may contribute to improving the outcomes of current lung cancer treatment.

Short tandem repeat polymorphism analysis for primary peritoneal choriocarcinoma: A case report and literature review.

The peritoneum is an extremely rare site for primary choriocarcinoma development. Primary peritoneal choriocarcinoma could be either gestational or nongestational, whereas it is straightforward to ascribe uterine or tubal choriocarcinoma to the gestational origin. Herein, we report a case of primary peritoneal choriocarcinoma that is genetically diagnosed as a gestational subtype originating from an occult complete hydatidiform mole. A 46-year-old female patient with two-time induced abortion histories underwent emergency laparotomy under clinical suspicion of ruptured tubal pregnancy. Laparotomy revealed a hemorrhagic tumor in the left mesosalpinx with apparently intact left ovary and fallopian tube. The excised tumor was pathologically diagnosed as choriocarcinoma. Multiplex short tandem repeat polymorphism analysis revealed an androgenetic/homozygous genotype tumor, identifying its origin as a complete hydatidiform mole. Our literature review of nine primary peritoneal choriocarcinoma cases, including ours, highlighted the importance of tumor genotyping in differentiating between gestational and non-gestational subtypes and identifying the causative pregnancy.

Dynamic conformal arc radiotherapy for locally advanced lung cancer: a comparison with static-beam conformal radiotherapy.

Background: This study investigated whether the dose distribution of lung cancer can be improved by dynamic arc conformal radiotherapy (dynamic CRT) compared with static multiple-beam radiotherapy (static CRT). Materials and methods: A dummy study of static CRT and dynamic CRT was performed, designed to meet the predetermined dose constraints. A dose of 60 Gy in 30 fractions was administered using two dose prescription methods: dose prescribed to the isocenter (IC prescription), and dose prescribed to > 50% of the planning target volume (D50 prescription). Dose-volume parameters were compared between the plans. Results: Among 20 patients with locally advanced lung cancer, dose conformity was significantly better with dynamic CRT than static CRT (median conformity index: 1.3 vs. 2.2; p < 0.01). As for the lung dose, compared with static CRT, dynamic CRT did not increase the percentage lung volume receiving ≥ 20 Gy (18.9% vs. 19.3%, p = 0.09). The maximum spinal cord dose was significantly reduced by dynamic CRT (static vs. dynamic CRT: 44.1 vs. 25.2 Gy, p < 0.001). With the change from IC to D50 prescription, the 95% isodose volume increased by 18.3 cc in static CRT and by 4.1 cc in dynamic CRT, while doses to the lung and spinal cord remained within the acceptable ranges. Conclusion: The dynamic CRT technique showed better target coverage and lower doses to the spinal cord in exchange for increased low-dose lung area, compared with static CRT. Dynamic CRT with D50 prescription instead of prescription to the isocenter has excellent dose distribution profiles without compromising doses to organs at risk for lung cancer at favorable locations.

A survey of physical and occupational therapists' views on lumbar loading movements.

[Purpose] To identify the lumbar loading movements necessary in clinical practice. [Participants and Methods] A questionnaire survey was conducted among physical and occupational therapists in Japan. There were no exclusion criteria regarding the number of years of experience, age, or field of employment. The participants were randomly selected and administered the questionnaire. They were asked to list and rank the lumbar loadings they considered necessary. [Results] A total of 739 respondents participated in the survey. The results of this nationwide survey indicated that the lifting movement of heavy objects in the trunk flexion position was the most common movement (for 354 participants). [Conclusion] The main loading movements of the lumbar spine were reported to be heavy lifting movements (in the trunk flexion position) and trunk rotation movements. As perspectives, we aim to conduct an analytical study of some of lumbar spine loading movements outlined in this study, using a musculoskeletal simulator and electromyography.

RNA Interference Targeting Liver Angiopoietin-Like Protein 3 Protects from Nephrotic Syndrome in a Rat Model Via Amelioration of Pathologic Hypertriglyceridemia.

Nephrotic syndrome (NS) is associated with metabolic perturbances including profound dyslipidemia characterized by hypercholesterolemia and hypertriglyceridemia. A major underlying mechanism of hypertriglyceridemia in NS is lipoprotein lipase (LPL) deficiency and dysfunction. There is emerging evidence that elevated angiopoietin-like protein 3 (ANGPTL3), an LPL inhibitor that is primarily expressed and secreted by hepatocytes, may be in part responsible for these findings. Furthermore, there is evidence pointing to the contribution of ANGPTL3 to the pathogenesis of proteinuria in NS. Therefore, we hypothesized that inhibition of hepatic ANGPTL3 by RNA interference will ameliorate dyslipidemia and other symptoms of NS and pave the way for a new therapeutic strategy. To this end, we used a subcutaneously delivered, GalNAc (N-Acetylgalactosamine)-conjugated small interfering RNA (siRNA) to selectively target and suppress liver Angptl3 in rats with puromycin-induced NS, which exhibits clinical features of NS including proteinuria, hypoalbuminemia, hyperlipidemia, and renal histologic abnormalities. The study demonstrated that siRNA-mediated knockdown of the liver Angptl3 relieved its inhibitory effect on LPL and significantly reduced hypertriglyceridemia in nephrotic rats. This was accompanied by diminished proteinuria and hypoalbuminemia, which are the hallmarks of NS, and significant attenuation of renal tissue inflammation and oxidative stress. Taken together, this study confirmed the hypothesis that suppression of Angptl3 is protective in NS and points to the possibility that the use of RNA interference to suppress hepatic Angptl3 can serve as a novel therapeutic strategy for NS. SIGNIFICANCE STATEMENT: The current standard of care for mitigating nephrotic dyslipidemia in nephrotic syndrome is statins therapy. However, the efficacy of statins and its safety in the context of impaired kidney function is not well established. Here, we present an alternate therapeutic approach by using siRNA targeting Angptl3 expressed in hepatocytes. As the liver is the major source of circulating Angptl3, siRNA treatment reduced the profound hypertriglyceridemia in a rat model of nephrotic syndrome and was also effective in improving kidney and cardiac function.

Diagnostic utility of metabolic parameters on FDG PET/CT for lymph node metastasis in patients with cN2 non-small cell lung cancer.

BACKGROUND: The aim of this study was to assess the diagnostic utility of metabolic parameters on fluorine-18-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET)/computed tomography (CT) for predicting lymph node (LN) metastasis in patients with cN2 non-small cell lung cancer (NSCLC). METHODS: We retrospectively reviewed patients who underwent surgery for cN2 NSCLC between 2007 and 2020. Those who had clinically diagnosed positive hilar and mediastinal LNs by routine CT and PET/CT imaging were investigated. To measure the metabolic parameters of LNs, the data according to maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and LN-to-primary tumor ratio of SUVmax (LPR) were examined. The diagnosis of each retrieved LN was confirmed based on histopathological examination of surgical tissue specimens. Receiver operating characteristics (ROC) curves with area under the curve (AUC) calculations and multivariate analysis by logistic regression were performed. RESULTS: Forty-five patients with 84 clinically diagnosed positive hilar or mediastinal LNs were enrolled in the present study. Of the 84 LNs, 63 LNs were pathologically proven as positive (75%). The SUVmax, MTV, TLG, and LPR of LN metastasis were significantly higher than those of benign nodes. In the ROC analysis, the AUC value of LPR [AUC, 0.776; 95% confidence interval (CI), 0.640-0.913] was higher than that of LN SUVmax (AUC, 0.753; 95% CI, 0.626-0.880) or LN TLG3.5 (AUC, 0.746; 95% CI, 0.607-0.885). Using the optimal LPR cutoff value of 0.47, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 84.1, 66.7, 88.3, 58.3, and 79.8%, respectively. Multivariate analysis by logistic regression showed that LPR was an independent predictor for LN metastasis (odds ratio, 6.45; 95% CI, 1.785-23.301; P = 0.004). In the subgroup analysis of adenocarcinoma patients (n = 18; 32 LNs), TLG3.5 was a better predictor (AUC, 0.816; 95% CI, 0.639-0.985) than LPR (AUC, 0.792; 95% CI, 0.599-0.986) or LN SUVmax (AUC, 0.792; 95% CI, 0.625-0.959). CONCLUSIONS: Our findings suggest that LPR on FDG-PET is a useful predictor for LN metastasis in patients with cN2 NSCLC. TLG can be a good predictor for LN metastasis in patients with adenocarcinoma.

Psoas muscle mass in patients undergoing lung cancer surgery: a prognostic difference between squamous cell carcinoma and adenocarcinoma.

BACKGROUND: Psoas muscle mass is a surrogate marker for sarcopenia: a depletion of skeletal muscle mass. This study was conducted to elucidate the prognostic significance of the psoas muscle index (PMI: cross-sectional area of the bilateral psoas muscle at the umbilical level on computed tomography/height2 [cm2/m2]) in patients undergoing surgery for lung squamous cell carcinoma (SCC) and lung adenocarcinoma (ADC). METHODS: One hundred and sixty-five patients with SCC and 556 patients with ADC who underwent R0 resection between 2007 and 2014 were reviewed for analysis. In SCC patients, the mean value (standard deviation) of the PMI was 6.15 (1.49) in men and 4.65 (1.36) in women. Among ADC patients, the PMI was 7.12 (1.60) in men and 5.29 (1.22) in women. Clinicopathological characteristics as well as the survival were evaluated. RESULTS: The PMI was associated with the age, body mass index (BMI), and serum albumin. In the multivariable Cox regression analysis, after adjusting for age, BMI, serum albumin, sex, pathological stage, and diffusing capacity for carbon monoxide, the PMI showed a significant association with the overall survival (OS) and disease-free survival (DFS) in SCC patients (hazard ratios 0.50 and 0.56, 95% confidence intervals 0.39-0.65 and 0.45-0.71, respectively). On the other hand, in ADC patients, the PMI had no impact on the OS or DFS. CONCLUSIONS: The PMI was significantly associated with the survival of lung SCC patients, but not of lung ADC patients, suggesting the presence of a previously unidentified relationship between skeletal muscle and lung SCC progression.

Verification of the diagnostic strategy for anterior mediastinal tumors.

BACKGROUND: For thymic epithelial tumors (TETs), the National Comprehensive Cancer Network guideline has suggested that complete excision of the tumor should be performed without a preoperative biopsy when resectable. However, little evidence has been provided to support this strategy. The purpose of this study was to review our diagnostic process and to evaluate the validity of radical resection of anterior mediastinal masses (AMMs) without pathological confirmation. METHODS: A total of 254 patients underwent surgical resection for AMMs between 2004 and 2015. This study included 181 patients with likely TETs according to clinical features, serum levels of tumor markers and autoimmune-antibodies, and radiological findings. In addition, AMMs likely TETs were classified into resectable or unresectable tumors. We retrospectively reviewed the diagnostic process of those patients and validated surgical resection of AMMs without a definitive diagnosis. RESULTS: Among 254 patients, 181 were suspected of having a TET based on the serum levels of tumor markers and autoimmune-antibodies and the radiological findings. Of them, 157 patients were deemed resectable and underwent surgical resection without histological confirmation, and 144 (92%) were diagnosed with TETs in the final pathological examinations. In 13 patients with non-TETs, the tumors were difficult to differentiate from TETs by imaging and clinical findings alone. CONCLUSIONS: A total of 92% of patients suspected of having a TET and who underwent complete resection without pathological confirmation were accurately diagnosed and properly treated. Surgical resection without a definitive diagnosis was feasible in patients suspected of having a TET when they were considered resectable.

Verification of T descriptor with consolidation size for sub-centimeter non-small cell lung cancer.

PURPOSE: In the most recent (eighth) edition of the TNM classification, the clinical T descriptor has been adapted to measure the consolidation size of sub-solid lung cancer. Sub-centimeter non-small cell lung cancer (NSCLC) has thereby been subclassified into three groups: Tis, T1mi, and T1a; however, the revision has not been validated well. Thus, we investigated the clinicopathological characteristics and long-term oncological outcomes of sub-centimeter NSCLCs based on the solid size. METHODS: The subjects of this retrospective review were 99 patients who underwent complete resection for NSCLC with ≤ 1 cm in consolidation size on computed tomography (CT). Survival was reanalyzed after reclassification according to the new TNM classification. RESULTS: This cohort consisted of 14 patients with cTis tumors, 18 with cT1mi tumors, and 67 with cT1a tumors. Among the patients with tumors classified as cT1a, two had lymph node metastasis and two had vascular invasion. The cumulative incidences of recurrence at 5 and 10 years were 0% for cTis/cT1mi tumors, and 4.5% and 6.1% for cT1a tumors, respectively. CONCLUSIONS: There may be pathological and survival differences between cTis/cT1mi tumors and cT1a tumors, but not between cTis tumors and cT1mi tumors.

The tumor doubling time is a useful parameter for predicting the histological type of thymic epithelial tumors.

PURPOSE: We assessed the utility of the tumor doubling time (TDT) for predicting the histological type of thymic epithelial tumors. METHODS: We retrospectively reviewed 130 patients with thymic epithelial tumors who underwent computed tomography two or more times before surgery. The patients were divided into low-risk thymoma (types A, AB and B1), high-risk thymoma (types B2 and B3) and thymic carcinoma (thymic carcinoma and thymic neuroendocrine tumor) groups. In the 96 patients who showed tumor enlargement, the relationship between the histological type and the TDT of the tumor was investigated. RESULTS: The study population included 55 men and 41 women from 26 to 82 years of age. The TDT of the thymic carcinoma group (median 205 days) was significantly shorter in comparison to the low-risk thymoma (median 607 days) and high-risk thymoma (median 459 days) groups. No significant differences were observed between the low-risk thymoma and high-risk thymoma groups. When we set the cutoff time for differentiating thymic carcinoma group from thymoma at 313 days, the sensitivity and specificity were 83.8% and 82.1%, respectively. CONCLUSIONS: The TDT is a useful parameter for differentiating between thymoma and thymic carcinoma group.

Membrane States of Saturated Glycerophospholipids: A Thermodynamic Study of Bilayer Phase Transitions.

Bilayer membranes formed by phospholipids vary in their membrane states by undergoing phase transitions in response to various external environmental factors. Pressure is one of these important environmental factors, but there are very few studies on the effects of pressure on phospholipid bilayer membranes. It is possible to deepen our understanding of the membrane states of phospholipid bilayer membranes by combining information regarding temperature- and/or ligand-responsivity with that regarding pressure-responsivity. In this review, we thermodynamically characterize the bilayer phase transitions of three kinds of saturated glycerophospholipids, each with a different polar head group (phosphatidyl-ethanolamine (PE), -choline (PC) or -glycerol (PG)), and explain their various membrane states depending on temperature and pressure. Both temperature- and pressure-responsivity reveal inherent features of these bilayer membranes: the metastability of the gel phase for PE bilayer membranes, the polymorphism of the gel phases for PC bilayer membranes and morphological changes in bilayer aggregates for PG bilayer membranes.

Thermotropic and barotropic phase transitions on diacylphosphatidylethanolamine bilayer membranes.

The bilayer phase transitions of four diacylphosphatidylethanolamines (PEs) with matched saturated acyl chains (Cn=12, 14, 16 and 18) and two PEs with matched unsaturated acyl chains containing a different kind of double bonds were observed by differential scanning calorimetry under atmospheric pressure and light-transmittance measurements under high pressure. The temperature-pressure phase diagrams for these PE bilayer membranes were constructed from the obtained phase-transition data. The saturated PE bilayer membranes underwent two different phase transitions related to the liquid crystalline (Lα) phase, the transition from the hydrated crystalline (Lc) phase and the chain melting (gel (Lß) to Lα) transition, depending on the thermal history. Pressure altered the gel-phase stability of the bilayer membranes of PEs with longer chains at a low pressure. Comparing the thermodynamic quantities of the saturated PE bilayer membranes with those of diacylphosphatidylcholine (PC) bilayer membranes, the PE bilayer membranes showed higher phase-transition temperatures and formed more stable Lc phase, which originates from the strong interaction between polar head groups of PE molecules. On the other hand, the unsaturated PE bilayer membranes underwent the transition from the Lα phase to the inverted hexagonal (HII) phase at a high temperature and this transition showed a small transition enthalpy but high pressure-responsivity. It turned out that the kind of double bonds markedly affects both bilayer-bilayer and bilayer-nonbilayer transitions and the Lα/HII transition is a volume driven transition for the reconstruction of molecular packing. Further, the phase-transition behavior was explained by chemical potential curves of bilayer phases.

Chela asymmetry in a durophagous crab: predominance of right-handedness and handedness reversal is linked to chela size and closing force.

The swimming crab Portunus trituberculatus is a durophagous brachyuran. Right-handed crabs are predominant, but left-handed crabs are also found in nature. Left-handedness may arise from loss of the right crusher. We examined whether heterochely (morphology) was correlated with differences in closing force (physical property) and handedness (behaviour). The closing force was stronger in larger chela with greater apodeme height and handedness resided in the chela with stronger closing force. With loss of the right chela (autotomy), handedness transitioned from the right to left chela, and all crabs were left-handed thereafter. Reversed handedness was accompanied with a reduction of size and closing force in the regenerated right chela, and growth of the original left chela. After handedness reversal, dentition on the left dactylus of the newly-converted crusher was close to that of the original right crusher, but did not attain the same shape, even after 10 moults. Left-handed crabs were significantly worse than right-handed crabs at crushing hard-shelled prey. Chela formation was symmetrical in the zoea, and heterochely and right-handedness started in the megalopa, regardless of maternal handedness. Since the left chela is capable of being the crusher, heterochely may be caused by differences in morphogenetic velocity between the right and left chelae, under a signal discriminating right from left. Right-handedness is an attribute of P. trituberculatus, that would be inheritable across generations. It is probable that right-handedness was used in the earliest durophagous crabs, and this trend has been succeeded to extant species.

How does acyl chain length affect thermotropic phase behavior of saturated diacylphosphatidylcholine-cholesterol binary bilayers?

Thermotropic phase behavior of diacylphosphatidylcholine (CnPC)-cholesterol binary bilayers (n=14-16) was examined by fluorescence spectroscopy using 6-propionyl-2-(dimethylamino)naphthalene (Prodan) and differential scanning calorimetry. The former technique can detect structural changes of the bilayer in response to the changes in polarity around Prodan molecules partitioned in a relatively hydrophilic region of the bilayer, while the latter is sensitive to the conformational changes of the acyl chains. On the basis of the data from both techniques, we propose possible temperature T-cholesterol composition Xch phase diagrams for these binary bilayers. A notable feature of our phase diagrams, including our previous results for diheptadecanoylphosphatidylcholine (C17PC) and distearoylphosphatidylcholine (C18PC), is that there is a peritectic-like point around Xch=0.15, which can be interpreted as indicating the formation of a 1:6-complex of cholesterol and CnPCs within the binary bilayer irrespective of the acyl chain length. We could give a reasonable explanation for such complex formation using the modified superlattice view. Our results also showed that the Xch value of the abolition of the main transition is almost constant for n=14-17 (ca. 0.33), while it increases to ca. 0.50 for n=18. By contrast, a biphasic n-dependence of Xch was observed for the abolition of the pretransition, suggesting that there are at least two antagonistic n-dependent factors. We speculate that this could be explained by the enhancement of the van der Waals interaction with increases in n and the weakening of the repulsion between the neighboring headgroups with decreases in n.

Thermotropic and barotropic phase behavior of phosphatidylcholine bilayers.

Bilayers formed by phospholipids are frequently used as model biological membranes in various life science studies. A characteristic feature of phospholipid bilayers is to undergo a structural change called a phase transition in response to environmental changes of their surroundings. In this review, we focus our attention on phase transitions of some major phospholipids contained in biological membranes, phosphatidylcholines (PCs), depending on temperature and pressure. Bilayers of dipalmitoylphosphatidylcholine (DPPC), which is the most representative lipid in model membrane studies, will first be explained. Then, the bilayer phase behavior of various kinds of PCs with different molecular structures is revealed from the temperature-pressure phase diagrams, and the difference in phase stability among these PC bilayers is discussed in connection with the molecular structure of the PC molecules. Furthermore, the solvent effect on the phase behavior is also described briefly.

Study on the subgel-phase formation using an asymmetric phospholipid bilayer membrane by high-pressure fluorometry.

The myristoylpalmitoylphosphatidylcholine (MPPC) bilayer membrane shows a complicated temperature-pressure phase diagram. The large portion of the lamellar gel (L(ß)'), ripple gel (P(ß)'), and pressure-induced gel (L(ß)I) phases exist as metastable phases due to the extremely stable subgel (L(c)) phase. The stable L(c) phase enables us to examine the properties of the L(c) phase. The phases of the MPPC bilayers under atmospheric and high pressures were studied by small-angle neutron scattering (SANS) and fluorescence spectroscopy using a polarity-sensitive fluorescent probe Prodan. The SANS measurements clearly demonstrated the existence of the metastable L(ß)I phase with the smallest lamellar repeat distance. From a second-derivative analysis of the fluorescence data, the line shape for the L(c) phase under high pressure was characterized by a broad peak with a minimum of ca. 460 nm. The line shapes and the minimum intensity wavelength (λ″(min)) values changed with pressure, indicating that the L(c) phase has highly pressure-sensible structure. The λ″(min) values of the L(c) phase spectra were split into ca. 430 and 500 nm in the L(ß)I phase region, which corresponds to the formation of a interdigitated subgel L(c) (L(c)I) phase. Moreover, the phase transitions related to the L(c) phase were reversible transitions under high pressure. Taking into account the fluorescence behavior of Prodan for the L(c) phase, we concluded that the structure of the L(c) phase is highly probably a staggered structure, which can transform into the L(c)I phase easily.

Docking simulation study and kinase selectivity of f152A1 and its analogs.

f152A1 is a potent inhibitor of MAP kinases and TNFα-transcription. When f152A1 and its analogs are assayed against ERK2, MEK1, and MEKK1, these compounds show different inhibition profiles. It is considered that the highly reactive cis-enone moiety and modifications of the 14-membered resorcylic lactone ring may determine their kinase selectivity and potency. In order to clarify the different potencies of these compounds toward MAP kinases, conformational analysis, molecular orbital studies, and docking simulation studies using model structures of ERK2, MEK1, and MEKK1 have been performed. These studies have revealed that (i) ligand binding does not depend on chemical bonding but on molecular interaction (molecular orbital analysis), (ii) the cis-enone moiety of inhibitors is in the range of Michael addition reaction with the Cys166 residue in ERK2 (docking simulation study), and (iii) molecular shape of M1(8) conformations is the best fit for the ATP binding site of kinases. Considering the molecular docking analysis of these inhibitors in these kinases, molecular shape will be most important to their corresponding kinases activities.