A case of Marfan syndrome with massive haemoptysis from collaterals of the lateral thoracic artery.

BACKGROUND: Marfan Syndrome (MFS) is a heritable connective tissue disorder with a high degree of clinical variability including respiratory diseases; a rare case of MFS with massive intrathoracic bleeding has been reported recently. CASE PRESENTATION: A 32-year-old man who had been diagnosed with MFS underwent a Bentall operation with artificial valve replacement for aortic dissection and regurgitation of an aortic valve in 2012. Warfarin was started postoperatively, and the dosage was gradually increased until 2017, when the patient was transported to our hospital due to sudden massive haemoptysis. Computed tomography (CT) with a maximum intensity projection (MIP) revealed several giant pulmonary cysts with fluid levels in the apex of the right lung with an abnormal vessel from the right subclavian artery. Transcatheter arterial embolization was performed with angiography and haemostasis was achieved, which suggested that the bleeding vessel was the lateral thoracic artery (LTA) branch. CT taken before the incident indicated thickening of the cystic wall adjacent to the thorax; therefore, it was postulated that the bleeding originated from fragile anastomoses between the LTA and pulmonary or bronchial arteries. It appears that the vessels exhibited inflammation that began postoperatively, which extended to the cysts. CONCLUSION: We experienced a case of MFS with massive haemoptysis from the right LTA. We have to be aware of the possibility that massive haemoptysis could be induced in MFS with inflamed pulmonary cysts.

Borderline pulmonary hypertension is associated with exercise intolerance and increased risk for acute exacerbation in patients with interstitial lung disease.

BACKGROUND: Pulmonary hypertension (PH) is traditionally defined as a resting mean pulmonary artery pressure (mPAP) of ≥25 mmHg, while mPAP in the range of 21 to 24 mmHg is recognized as "borderline PH." Interstitial lung disease (ILD) is complicated by the development of PH, which is known to be linked with exercise intolerance and a poor prognosis. Even though it has recently been recommended that PH is redefined as a mPAP of > 20 mmHg, little is known about the clinical significance of borderline PH in ILD. We evaluated whether borderline PH has an impact on the exercise capacity, risk of acute exacerbation (AE), and mortality in patients with ILD. METHODS: A total of 80 patients with ILD who underwent right heart catheterization (RHC) between November 2013 and October 2016 were included. The patients were divided into 3 groups according to the mPAP values: mPAP ≤20 mmHg (No-PH group; n = 56), 20 < mPAP < 25 mmHg (Bo-PH group; n = 18), and mPAP ≥25 mmHg (PH group; n = 6). The demographic, hemodynamic, spirometric, and 6-min walk test (6MWT) data of the patients were collected. In addition, the 1-year incidence of AEs and 1-year survival of the patients after the initial RHC were also evaluated. RESULTS: There were no significant differences among the 3 groups in the mean age, pulmonary function parameters or the PaO2, however, 6-min walk distance was significantly lower in both the Bo-PH and PH groups (p < 0.001 for both) as compared to the No-PH group. The results of the Kaplan-Meier analysis revealed that while there was no significant difference in the 1-year survival rate among the three groups, the 1-year incidence of AEs was significantly higher in both the Bo-PH and PH groups (p < 0.001, p = 0.023, respectively) as compared to the No-PH group. CONCLUSIONS: The current study suggested that borderline PH may be associated with poorer exercise tolerance and an increased risk of AEs in patients with ILD. Therefore, the physicians should pay close attention to the presence of even mild elevation of the mPAP at the initial evaluation in patients with ILD.

A case of airway aluminosis with likely secondary pleuroparenchymal fibroelastosis.

BACKGROUND: Excessive inhalation of aluminium powder occasionally results in upper lobe predominant lung fibrosis, which is similar to idiopathic pleuroparenchymal fibroelastosis (IPPFE) and has been suggested to be secondary PPFE. CASE PRESENTATION: A 67-year-old man who had worked in an aluminum-processing factory for 50 years visited our hospital complaining of exertional dyspnea. Chest computed tomography (CT) showed bilateral dense sub-pleural consolidation in the upper and middle lung fields, which was consistent with IPPFE; however, the possibility of secondary PPFE associated with aluminosis was not ruled out. Considering the patient's critical condition, trans-bronchial lung biopsy (TBLB) rather than surgical lung biopsy was performed, with elemental analysis of the biopsied specimen. Unfortunately, the specimen obtained by TBLB did not contain alveolar tissue; therefore, pathological diagnosis of PPFE was not possible. However, radiographic findings were highly suggestive of PPFE. On elemental analysis, excessive amounts of aluminum were detected in the bronchiolar walls, establishing a diagnosis of airway aluminosis with likely secondary PPFE resulting from aluminium exposure. CONCLUSIONS: TBLB with elemental analysis might be useful in differentiating idiopathic PPFE from secondary causes in dust inhalation related disease, such as aluminosis. This case indicated that inhalation of aluminium might cause secondary PPFE, with attention needing to be paid to avoid further exposure.

Evaluation of the metabolic chiral inversion of d-selenomethionine in rats by stable isotope dilution gas chromatography-mass spectrometry.

The stereoselective pharmacokinetics of selenomethionine enantiomers in rats has been studied to evaluate the chiral inversion of D-selenomethionine to the L-enantiomer. After bolus intravenous administration of D- or L-selenomethionine to rats, the plasma concentrations of these two enantiomers were determined by stereoselective gas chromatography-mass spectrometry with selected ion monitoring. This method involved derivatization of selenomethionine enantiomers with HCl in methanol to form methyl ester followed by N-acylation with (+)-α-methoxy-α-trifluoromethylphenylacetyl chloride to form the diastereomeric amide, and separation of the diastereomer on GC with an achiral column. Plasma concentrations of administered D- and L-selenomethionine declined with terminal half-lives of 96 ± 17 min and 91 ± 6 min, respectively. L-Selenomethionine appeared rapidly in plasma after administration of D-selenomethionine, whereas D-selenomethionine was not detected in plasma after administration of L-selenomethionine. The fraction of conversion of D-selenomethionine to L-selenomethionine was estimated to be 61.3 ± 14.5%. The present method evaluates the stereoselective pharmacokinetics of selenomethionine enantiomers, including the estimation of the metabolic chiral inversion.

[A case of estrogen receptor-positive metastatic breast cancer in a postmenopausal woman treated with ethinyl estradiol].

The patient was 77-year-old woman whose breast cancer had metastasized to the bone and soft tissue 5 years after surgery. Although she had been sequentially treated with endocrine therapies following chemotherapies, new metastatic lesions in the pleura and skin appeared 8 years after recurrence. The biopsied skin tissue showed high positivity for estrogen receptor(ER), was negative for human epidermal growth factor receptor 2(HER2), and had a low Ki-67 labeling index. Following the treatment with exemestane(EXE)for 3 months, ethinyl estradiol(EE2)was administered at 3mg/day. After 4 months of treatment, the lymph nodes shrunk to 35% of their size and pleural effusion disappeared. The efficacy of EE2 was observed for 10 months. Subsequently, fulvestrant was administered because the skin lesions showed progressive disease. Adverse events such as nausea and general fatigue were observed at the beginning of EE2 therapy. Pigmentation of the nipple and areola and cystic swelling of the cervical canal were observed after a few months. This therapy can be considered to be effective in patients with ER-positive metastatic breast cancer who have been heavily treated with endocrine therapies and chemotherapies.

Synthesis and characterization of amino acid deletion analogs of κ-hefutoxin 1, a scorpion toxin on potassium channels.

Nine analogs of scorpion toxin peptide κ-hefutoxin 1 were synthesized by stepwise deletion of its amino acid residues. Disulfide bond pairings of the synthetic analogs were confirmed by enzymatic digestion followed by MALDI-TOF-MS measurements. Functional characterization shows that analogs in which N-terminal residues were deleted retained biological activity, whereas deletion of middle part residues resulted in loss of activity. Furthermore, κ-hefutoxin 1 and analogs were subjected to a screening on voltage-gated potassium channels in order to determine their subtype selectivity. It is shown that κ-hefutoxin 1 is suitable as template for peptidomimetics in order to design small peptide-based therapeutic compounds.

Enhanced transgene expression from chromatinized plasmid DNA in mouse liver.

Plasmid DNA was chromatinized with core histones (H2A, H2B, H3, and H4) in vitro and was delivered into mouse liver by hydrodynamics-based administration. Transgene expression from the chromatinized plasmid DNA was more efficient than that from plasmid DNA delivered in the naked form. The use of acetylation-enriched histones isolated from cells treated with a histone deacetylase inhibitor (trichostatin A) seemed to be more effective. These results indicated that chromatinized plasmid DNA is useful for efficient transgene expression in vivo.

Cancer mortality among atomic bomb survivors exposed as children.

OBJECTIVES: To compare cancer mortality among A-bomb survivors exposed as children with cancer mortality among an unexposed control group (the entire population of Japan, JPCG). METHODS: The subjects were the Hiroshima and Nagasaki A-bomb survivor groups (0-14 years of age in 1945) reported in life span study report 12 (follow-up years were from 1950 to 1990), and a control group consisting of the JPCG. We estimated the expected number of deaths due to all causes and cancers of various causes among the exposed survivors who died in the follow-up interval, if they had died with the same mortality as the JPCG (0-14 years of age in 1945). We calculated the standardized mortality ratio (SMR) of A-bomb survivors in comparison with the JPCG. RESULTS: SMRs were significantly higher in exposed boys overall for all deaths, all cancers, leukemia, and liver cancer, and for exposed girls overall for all cancers, solid cancers, liver cancer, and breast cancer. In boys, SMRs were significantly higher for all deaths and liver cancer even in those exposed to very low doses, and for all cancers, solid cancers, and liver cancer in those exposed to low doses. In girls, SMRs were significantly higher for liver cancer and uterine cancer in those exposed to low doses, and for leukemia, solid cancers, stomach cancer, and breast cancer in those exposed to high doses. CONCLUSIONS: We calculated the SMRs for the A-bomb survivors versus JPCG in childhood and compared them with a true non-exposed group. A notable result was that SMRs in boys exposed to low doses were significantly higher for solid cancer.

Transgene expression efficiency from plasmid DNA delivered as a complex with histone H3.

The intranuclear disposition of plasmid DNA is extremely important for transgene expression. Exogenous histones have been used as carriers of plasmid DNA in histone-mediated gene delivery. In this study, the effects of exogenous histone H3 complexed with plasmid DNA on transgene expression efficiency were examined. The plasmid-histone complexes in various ratios were transfected into HeLa cells by osmotic pressure. Histone H3 suppressed transgene expression in the nucleus in a dose-dependent manner. Our results suggest that the histone-mediated gene delivery is unlikely to be useful, from the viewpoint of the intranuclear disposition.

An adult norovirus-related encephalitis/encephalopathy with mild clinical manifestation.

Norovirus is an emerging pathogen that causes gastroenteritis outbreaks. Here, we reported an adult female case of norovirus-related encephalitis/encephalopathy (NvREE) with abnormal behaviour, apathy, motor aphasia, bradykinesia and gait disturbance. We treated the patient with intravenous methyl-prednisolone pulse therapy and she recovered quickly. There were slight abnormal signals in the cortex of the opercular part and insula on the MRI fluid-attenuated inversion-recovery (FLAIR) image, generalised slow wave as a background activity in her EEG and cerebrospinal fluid pleocytosis, which restored soon after her recovery. We successfully detected the norovirus genome in stool samples from all seven family members. This is a first case report of an adult NvREE with detection of pathogenic evidence. There could be more cases of NvREE with mild neuropsychiatric symptoms, considering the increasing outbreaks each year.

Effects of non-B DNA sequences on transgene expression.

DNA conformation may be an important factor affecting gene transcription. In this study, we examined how DNA sequences with unusual conformations affect transgene expression. A(30) and (CG)(15) sequences that can adopt the B' and Z conformations, respectively, were introduced into a beta-actin promoter. Luciferase plasmids containing the manipulated promoter were transfected into NIH3T3 cells by electroporation and were delivered into mouse livers with a hydrodynamics-based injection. Expression from plasmid with the (CG)(15) sequence was multiple times higher than expression from control plasmid DNA. The A(30) sequence also tended to enhance expression. These results suggest that non-B DNA sequences could improve transgene expression in cells.

Missense mutation in Abcg5 in SHRSP rats does not accelerate intestinal absorption of plant sterols: comparison with Wistar rats.

Stroke-prone spontaneously hypertensive rats (SHRSP) deposit plant sterols in their bodies and have a mutation in ATP binding cassette transporter G5 (Abcg5). Lymphatic recovery rates of campesterol and sitosterol in SHRSP rats were comparable to those in Wistar rats, a strain that does not deposit plant sterols in the body and has no mutation in Abcg5. Higher absorption of stigmasterol and sitostanol was observed in SHRSP rats than in Wistar rats, but the differences between SHRSP and Wistar rats were quite small, because the absorbed amounts of these two sterols were much lower than those of campesterol and sitosterol. The in situ uptake of (3)H-sitosterol and (14)C-cholesterol solubilized in the bile salt micelle into intestinal mucosa was comparable between SHRSP and Wistar rats. These observations suggest that a mutation in Abcg5 does not greatly influence intestinal absorption of plant sterols in SHRSP rats, at least in comparison with Wistar rats.

Comparison of effects of dietary unesterified and esterified plant sterols on cholesterol absorption in rats.

Effects of dietary unesterified plant sterols and plant sterol oleates and stearates on absorption and metabolism of cholesterol were compared in rats fed a cholesterol-supplemented diet. Fecal excretion of neutral steroids (cholesterol plus coprostanol) in rats fed unesterified plant sterols or plant sterol oleates was significantly higher than in those fed the control diet or plant sterol stearates. Deposition of cholesterol in the liver was significantly lower in rats fed unesterified plant sterols or plant sterol oleates than in those fed the control diet or plant sterol stearates. No significant difference was observed in fecal excretion of cholesterol plus coprostanol and hepatic cholesterol concentration between unesterified plant sterols and plant sterol oleates. Unesterified plant sterols were significantly more effective to reduce lymphatic recovery of radiolabeled cholesterol given to the stomach than plant sterol oleates. Although our observations suggest a possibility that unesterified plant sterols are potentially more effective to inhibit cholesterol absorption than plant sterol oleates in rats, difference in the activity is substantially small between these two forms of plant sterols.

Solubility in and affinity for the bile salt micelle of plant sterols are important determinants of their intestinal absorption in rats.

Intestinal absorption of various plant sterols was investigated in thoracic duct-cannulated normal rats. Lymphatic recovery was the highest in campesterol, intermediate in brassicasterol and sitosterol, and the lowest in stigmasterol and sitostanol. Higher solubility in the bile salt micelle was observed in sitosterol, campesterol, and sitostanol than in brassicasterol and stigmasterol. The solubility of the latter two sterols was extremely low. When the affinity of plant sterols for the bile salt micelle was compared in an in vitro model system, which assessed sterol transfer from the micellar to the oil phase, the transfer rate was the highest in brassicasterol, intermediate in campesterol and stigmasterol, and lowest in sitosterol and sitostanol. Although no significant correlations between lymphatic recovery of plant sterols and their micellar solubility or transfer rate from the bile salt micelle were observed, highly positive correlation was obtained between the lymphatic recovery and the multiplication value of the micellar solubility and the transfer rate. These observations strongly suggest that both solubility in and affinity for the bile salt micelle of plant sterols are important determinants of their intestinal absorption in rats.

Tea catechins with a galloyl moiety suppress postprandial hypertriacylglycerolemia by delaying lymphatic transport of dietary fat in rats.

Tea catechins, (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin gallate (EGCG), have been shown to be epimerized to (-)-catechin (C), (-)-gallocatechin (GC), (-)-catechin gallate (CG), and (-)-gallocatechin gallate (GCG), respectively, during heat treatment. In this study, we examined the effect of tea catechins rich in ECG and EGCG and heat-treated tea catechins rich in CG and GCG on postprandial hypertriacylglycerolemia in rats. Both tea catechins and heat-treated tea catechins suppressed postprandial hypertriacylglycerolemia. Lymphatic recovery of (14)C-trioleoylglycerol in rats cannulated in the thoracic duct was delayed by the administration of tea catechins and heat-treated tea catechins. Tea catechins and heat-treated tea catechins had the same effect on all variables tested. These catechin preparations dose-dependently inhibited the activity of pancreatic lipase in vitro. When purified catechins were used, only those with a galloyl moiety inhibited the activity of pancreatic lipase. These results suggest that catechins with a galloyl moiety suppress postprandial hypertriacylglycerolemia by slowing down triacylglycerol absorption through the inhibition of pancreatic lipase. Because postprandial hypertriacylglycerolemia is a risk factor for coronary heart disease, our results suggest that catechins with a galloyl moiety may prevent this disease.

A new prenylated flavonoid from propolis collected in Okinawa, Japan.

The new prenylflavonoid, isonymphaeol-B (1), together with three known compounds, nymphaeol-A (2), nymphaeol-B (3), and nymphaeol-C (4), were isolated from propolis collected in Okinawa, the southern-most prefecture of Japan. The structure of each compound was determined by spectral methods, including mass spectrometry and 2D NMR. Each compound had 1,1-diphenyl-2-picryl-hydrazyl radical-scavenging activity.

Heat-epimerized tea catechins rich in gallocatechin gallate and catechin gallate are more effective to inhibit cholesterol absorption than tea catechins rich in epigallocatechin gallate and epicatechin gallate.

It has been known that tea catechins, (-)-epicatechin (1), (-)-epigallocatechin (2), (-)-epicatechin gallate (3), and (-)-epigallocatechin gallate (4) are epimerized to(-)-catechin (5), (-)-gallocatechin (6), (-)-catechin gallate (7), and (-)-gallocatechin gallate (8), respectively, during retort pasteurization. We previously reported that tea catechins, mainly composed of 3 and 4, effectively inhibit cholesterol absorption in rats. In this study, the effect of heat-epimerized catechins on cholesterol absorption was compared with tea catechins. Both tea catechins and heat-epimerized catechins lowered lymphatic recovery of cholesterol in rats cannulated in the thoracic duct and epimerized catechins were more effective than tea catechins. The effect of purified catechins on micellar solubility of cholesterol was examined in an in vitro study. The addition of gallate esters of catechins reduced micellar solubility of cholesterol by precipitating cholesterol from bile salt micelles. Compounds 7 and 8 were more effective to precipitate cholesterol than 3 and 4, respectively. These observations strongly suggest that heat-epimerized catechins may be more hypocholesterolemic than tea catechins.