Operative Results and Clinical Features of Chronic Stanford Type B Aortic Dissection: Examination of 234 Patients Over 6 Years.

OBJECTIVE/BACKGROUND: Recently, the indications for thoracic endovascular aortic repair (TEVAR) have been expanding, and the applicability of TEVAR for acute type B aortic dissection (TBAD) is proposed with regard to the high mortality of open surgery for chronic TBAD. TEVAR in the acute phase may lead to remodeling of the false lumen (FL), but it is controversial whether it completely resolves the aortic expansion in the chronic phase. In this study, operative results and the relationship between FL status and the time before surgical intervention were retrospectively analyzed. METHODS: From January 2008 to September 2013, 234 patients underwent open surgery for chronic TBAD. Most patients were on left heart bypass. By considering Japanese aortic disease treatment guidelines and the smaller physique of Japanese patients, operative indications were aneurysm >50 mm in diameter or rapid aneurysm enlargement of >5 mm in a 6 month period. RESULTS: In 180 cases, the FL was patent. The mean interval between onset of TBAD and operation was 61 ± 54 months. There was no significant difference between patients in the patent FL group and those in the thrombosed FL group (p = .44). Mean ratio of FL diameter to maximum aortic diameter (FL/AD) was 0.64 ± 0.21. There was no correlation between FL and AD before the operation (r = .12). Descending thoracic aortic replacement (DTAR) was performed in 127 cases and thoracic ascending aortic replacement (TAAR) in 107 cases (Crawford type I, n = 9; Crawford type II, n = 65; Crawford type III and IV, n = 22, respectively; Safi type V, n = 11). The overall operative mortality was 6.8%: 3.9% (5/127) for DTAR and 10.3% (11/107) for TAAR. The three year survival was 86.7, and the freedom from re-intervention rate was 97.0%. CONCLUSION: Enlargement of uncomplicated TBAD in the chronic phase was poorly related to FL status and the results of open repair have improved. However, further prospective study is necessary.

Genome-wide association study of degenerative bony changes of the temporomandibular joint.

OBJECTIVES: To identify susceptibility genes underlying degenerative bony changes of the temporomandibular joint (TMJ). MATERIALS AND METHODS: Bony changes of the TMJ condylar head were diagnosed by examination of panoramic radiographs and/or magnetic resonance images and/or computed tomography images. We conducted a genome-wide association study (GWAS) of 146 cases with TMJ degeneration and 374 controls from East Asian populations using an Illumina HumanOmniExpress BeadChip. After rigorous quality-control filtering, approximately 550,000 single nucleotide polymorphisms (SNPs) were used for tests of associations with disease status. RESULTS: Forty-one SNPs at 22 independent loci showed association signals at P < 1 × 10(-4). The SNP rs878962, which maps on an intron of TSPAN9 on chromosome 12, showed the strongest association (combined OR = 1.89, 95% confidence interval = 1.43-2.50, P = 8.1 × 10(-6)). According to in silico predictions of the 41 SNPs, two intronic SNPs of APOL3 (rs80575) and MRC2 (rs2460300) may fall within regulatory elements and affect DNA-protein interactions. We could not replicate SNPs located on genes that have been reported to be associated with temporomandibular disorder or temporomandibular osteoarthritis in previous studies at P < 1 × 10(-4). CONCLUSIONS: Our GWAS identified 22 independent loci showing suggestive association signals with degenerative bony changes of the TMJ. These loci provide good candidates for future follow-up studies.

Alpha-melanocyte-stimulating hormone contributes to an anti-inflammatory response to lipopolysaccharide in male C57BL6/J mice.

OBJECTIVE: During infection, metabolism and immunity react dynamically to promote survival through mechanisms that remain unclear. Pro-opiomelanocortin (POMC) cleavage products are produced and released in the brain and in the pituitary gland. One POMC cleavage product, alpha-melanocyte-stimulating hormone (α-MSH), is known to regulate food intake and energy expenditure and has anti-inflammatory effects. However, it is not known whether α-MSH is required to regulate physiological anti-inflammatory responses. We recently developed a novel mouse model with a targeted mutation in Pomc (Pomctm1/tm1 mice) to block production of all α-MSH forms which are required to regulate metabolism. To test whether endogenous α-MSH is required to regulate immune responses, we compared acute bacterial lipopolysaccharide (LPS)-induced inflammation between Pomctm1/tm1 and wild-type Pomcwt/wt mice. METHODS: We challenged 10 to 14-week-old male Pomctm1/tm1 and Pomcwt/wt mice with single i.p. injections of either saline or low-dose LPS (100 µg/kg) and monitored immune and metabolic responses. We used telemetry to measure core body temperature (Tb), ELISA to measure circulating cytokines, corticosterone and α-MSH, and metabolic chambers to measure body weight, food intake, activity, and respiration. We also developed a mass spectrometry method to measure three forms of α-MSH produced in the mouse hypothalamus and pituitary gland. RESULTS: LPS induced an exaggerated immune response in Pomctm1/tm1 compared to Pomcwt/wt mice. Both groups of mice were hypoactive and hypothermic following LPS administration, but Pomctm1/tm1 mice were significantly more hypothermic compared to control mice injected with LPS. Pomctm1/tm1 mice also had reduced oxygen consumption and impaired metabolic responses to LPS compared to controls. Pomctm1/tm1 mice had increased levels of key proinflammatory cytokines at 2 h and 4 h post LPS injection compared to Pomcwt/wt mice. Lastly, Pomcwt/wt mice injected with LPS compared to saline had increased total α-MSH in circulation 2 h post injection. CONCLUSION: Our data indicate endogenous α-MSH contributes to the inflammatory immune responses triggered by low-dose LPS administration and suggest that targeting the melanocortin system could be a potential therapeutic for the treatment of sepsis or inflammatory disease.

Anti-obesity compounds in green leaves of Eucommia ulmoides.

The anti-hypertensive effect of Eucommia leaves has been confirmed clinically, and the study of their anti-obesity properties has advanced. However, the compounds involved in their anti-obesity effect have not been fully elucidated. In this Letter, we examined the anti-obesity effect of Eucommia green leaf extract (EGLE) divided into five fractions with high porous polystyrene gel and of the compounds isolated, geniposidic acid, asperuloside and chlorogenic acid, respectively. A metabolic syndrome-like clinical model in mice was generated by feeding a 40% high-fat diet to examine the anti-obesity effects of chronic administration of test substance. After 4 weeks, body weight, white adipose tissue weight, plasma triglyceride levels and total cholesterol levels in the model mice were significantly inhibited by the 30% MeOH fraction (containing much higher levels of asperuloside than the other fractions), and these effects were similar to those of EGLE. Chronic administration of isolated asperuloside in Eucommia leaves suppressed increases in model mouse body weight, white adipose tissue weight, plasma triglyceride levels and free fatty acids levels. These results suggest that asperuloside in Eucommia leaves has important anti-obesity effects.

Long-term prognosis of patients with major depression and silent cerebral infarction.

OBJECTIVE: Many studies have examined the effects of cerebrovascular changes on treatment response in geriatric depression. However, few such studies have examined the relationship between cerebrovascular changes and long-term prognosis. We examined the effects of cerebrovascular changes on the course of geriatric depressive symptoms, dementia rates, and mortality over a follow-up period of approximately 10 years. METHOD: Participants were 84 patients with major depression (age of onset over 50 years); patients suffering from strokes, neurological disorders, and other psychiatric disorders were excluded. Magnetic resonance imaging findings were used to classify all patients into silent cerebral infarction (SCI)-positive (n = 37) or SCI-negative groups (n = 47). Prognoses were ascertained using a review of clinical charts and mailed questionnaires. RESULTS: Only 5% of patients with SCI were able to maintain remission whereas 36% of patients without SCI were able to do so. Total duration of depressive episodes was significantly longer in the SCI-positive group than in the SCI-negative group. SCI was also associated with a higher risk of dementia. CONCLUSION: The results of this long-term follow-up study demonstrate that the presence of SCI is associated with a relatively poor prognosis in geriatric depression.

[Pulmonary schwannoma with hypervascularity; report of a case].

A 54-year-old female was admitted to our hospital with a mass shadow in the right pulmonary hilum. The chest computed tomography (CT) scan revealed a well-circumscribed mass in the lower lobe of the right lung. Bronchoscopic examination showed a submucosal tumor in the right basal bronchus which bled easily, and the angiogram showed a tumor with hypervascularity. The tumor was suspected to be a sclerosing hemangioma or malignant tumor. A right basal segmentectomy was performed, and the pathological diagnosis was that of schwannoma. During the 8 year follow-up period, she exhibited no evidence of recurrence.

Increase in transforming growth factor-beta in the brain during infection is related to fever, not depression of spontaneous motor activity.

When viral infection occurs, this information is transmitted to the brain, and symptoms such as fever and tiredness are induced. One of the causes of these symptoms is the secretion of proinflammatory cytokines in blood and the brain. In this study, the i.p. administration of polyinosinic:polycytidylic acid (poly I:C), a synthetic double-stranded RNA, to rats was used as an infection model. Poly I:C decreased spontaneous motor activity (SMA) 2 h after i.p. administration, and this decrease was maintained thereafter. The concentration of active transforming growth factor-beta (TGF-beta) in cerebrospinal fluid (CSF) increased 1 h after the administration. This increase occurred earlier than those in the concentrations of other proinflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), in serum. The intracisternal administration of an anti-TGF-beta antibody partially inhibited fever induced by poly I:C administration; however, this treatment did not affect the decrease in SMA. Furthermore, intracisternal administration of TGF-beta raised the body temperature. These results indicate that TGF-beta in the brain, which was increased by poly I:C administration, is associated with fever but not with a decrease in SMA.

The hypothalamic regulation of metabolic adaptations to exercise.

Our modern lifestyle is characterised by easy access to nutrient dense foods combined with limited physical activity. A sedentary lifestyle is one of several factors that have contributed to the global obesity epidemic and it also predisposes to chronic illnesses such as diabetes and cardiovascular disease. Although many studies have focused on the benefits of exercise in peripheral tissues, the contributions of the central nervous system to these exercise-induced metabolic adaptations are relatively unknown. The present review highlights the role of the ventromedial hypothalamus in regulating the metabolic response to exercise.

Rapid Communication: MiR-92a as a housekeeping gene for analysis of bovine mastitis-related microRNA in milk.

Our aim was to identify a suitable microRNA housekeeping gene for real-time PCR analysis of bovine mastitis-related microRNA in milk. We identified , , and as housekeeping gene candidates on the basis of previous Solexa sequencing results. Threshold cycle (CT) values for , , and did not differ between milk from control cows and milk from mastitis-affected cows. NormFinder software identified as the most stable single housekeeping gene. We evaluated the suitability of the housekeeping gene candidates by using them to assess expression levels of the inflammation-related gene . Regardless of the housekeeping gene candidates used for normalization, relative expression levels of were significantly higher in mastitis-affected samples than in control samples. However, of all the housekeeping genes and gene combinations investigated, normalization with alone generated the difference in relative expression between mastitis-affected and control samples with the highest significance. These results suggest that is suitable for use as a housekeeping gene for analysis of bovine mastitis-related microRNA in milk.

Monozygotic twins discordant for primary aldosteronism: a case report.

This corrects the article DOI: 10.1038/jhh.2017.41.

Clinical and financial impact of obesity on the outcome of liver transplantation.

The purpose of this study was to determine whether body mass index (BMI) influences the clinical outcomes and overall cost of transplantation in adult liver transplantation (OLT) using records of 700 adult OLT recipients. Patients were divided into BMI range groups over the range of 15 to 42 (mean = 26.7), namely: <25, n = 288 (41%); 25 to 30, n = 245 (35%); > or =30, n = 167 (24%). Only a small subset of this last group was morbidly obese (BMI > or = 35, n = 37, 5% of total). We did not detect an effect of BMI on patient or graft survival, the incidence of acute graft rejection, or major surgical complications. BMI was not related to length of hospital stay. There were no statistical differences between the three groups with respect to the ratio of overall hospital cost in a general linear model, corrected for age, gender, calculated Model for End-Stage Liver Disease score, retransplant status, or return to the operating room. In conclusion, obesity did not influence either the costs or the clinical outcomes following OLT. Further analysis of the morbidly obese population with respect to cost and outcome is warranted.

Effect of early recurrence of hepatitis C on late biliary anastomotic stricture after liver transplantation.

The aim of the current study was to clarify whether recurrence of hepatitis C (HCV) infection affects biliary complications after liver transplantation (OLT), with special reference to late biliary anastomotic strictures (LBAS). We reviewed 665 consecutive adult OLT recipients with a choledochocholedochostomy without T-tube placement between 1990 and 2005. Biliary anastomotic stricture was confirmed by ERCP. The LBAS was defined as stricture that occurred 30 days or more after OLT. Recurrence of HCV was diagnosed by histological examination using liver biopsy specimen and confirmed by the presence of HCV-RNA. Early HCV recurrence was defined as recurrence that occurred within 6 months after OLT; LBAS occurred in 54 patients (8% of total). Mean duration from OLT to occurrence of LBAS was 6.9 months (1-44 months). Patients with HCV infection had higher occurrence of LBAS than did non-HCV patients (11% vs 5%, P = .0093). Among HCV patients, those with early HCV recurrence had exclusively high rate of LBAS (16%). In multivariate analyses, early recurrence of HCV (P < .001, relative risk [RR] 6.4), as well as occurrence of HAT (P = .0018, RR 8.0), and prolonged CIT (P = .034, RR 3.3) were independent risk factors affecting LBAS. In conclusion, patients with HCV infection have increased occurrence of LBAS after OLT. Additionally, early recurrence of HCV contributes to a higher rate of LBAS.

Background values for evaluation of heavy metal contamination in sediments.

The contamination of sediments can be evaluated from comparison of the current concentration with the estimated background value. Although it is known that grain size affects background concentrations, there have been difficulties in evaluating this effect. The specific surface area of sediments, which can be calculated from the grain size distribution, is introduced as a property index for correlation of background values. The results show that for sandy-to-sandy silt sediments, the background values of metals are expressed in terms of fines content, which can be correlated with the corresponding specific surface area. However, for silty clay or clayey silt sediments, which would have a high metal retention capacity, the level of the background may be constrained by the relatively low concentrations of metals in seawater. Finally, background levels of Zn, Cu and Pb are presented.

The growth hormone (GH) gene is expressed in the lateral hypothalamus: enhancement by GH-releasing hormone and repression by restraint stress.

Recent studies suggest that GH may modulate emotion, behavior, or stress response by its direct actions on the brain, and possible expression of the GH gene in the brain has been predicted. In this study we have investigated whether and where the GH gene is expressed in the brain and how it is regulated. Ribonuclease protection assay and 5'-rapid amplification of complementary DNA ends-PCR analyses indicated that the GH gene was expressed in rat brain, initiating at the identical transcription start point as that for pituitary GH gene expression. The brain GH messenger RNA was predominantly detected in the lateral hypothalamus (lh) by in situ reverse transcription-PCR analysis. GH gene expression in the brain was significantly enhanced by GH-releasing hormone administration and was rapidly repressed by exposure to restraint stress in the water, whereas the changes in pituitary GH messenger RNA contents in these circumstances were relatively smaller. The results of the present study suggest that the brain GH is predominantly expressed in lh under the control of physiological conditions to play a role in the modulation of brain functions.

Restraint stress enhances the gene expression of prolactin receptor long form at the choroid plexus.

Hormonal control of brain functions is considered to be important in the tolerance of stress, and it is now established that stress elevates serum PRL levels in male or cycling female rats. To investigate whether or how serum PRL acts on the brain during exposure to stress, we analyzed serum PRL levels and the gene expression of brain PRL receptors in rats subjected to restraint stress in the water (RSW). The serum PRL concentration was remarkably increased within 30 min in the rats by exposure to RSW and decreased to the initial level after 4 h of RSW, remaining at this level for up to 7 h of RSW. After the rats were released from the stress, the serum PRL level was significantly lowered in 6 h. Ribonuclease protection assay and in situ hybridization analysis revealed that messenger RNA (mRNA) expression for the long form PRL receptor [PRL-R(L)] was remarkably induced in the rat choroid plexus in 2 h of RSW. The high expression level of PRL-R(L) mRNA in the region was reduced after the rats were released from the stress. PRL-R(L) mRNA expression in the hypothalamus was at lower levels than those in the choroid plexus before and during the RSW treatment. The short form PRL receptor mRNA expression in the rat brain was considerably lower than expression of the long form receptor mRNA before or during RSW. The results indicated that the restraint stress caused a rapid increase in serum PRL and induced the gene expression for PRL-R(L) in the choroid plexus, suggesting stress-induced and choroid plexus PRL-R(L)-mediated transport of serum PRL into the cerebrospinal fluid.

A novel use of chitosan as a hypocholesterolemic agent in rats.

A series of experiments with male rats clearly demonstrated the hypocholesterolemic activity of dietary chitosan. On feeding a high cholesterol diet for 20 days, addition of 2 to 5% chitosan resulted in a significant reduction, by 25 to 30%, of plasma cholesterol without influencing food intake and growth. The concentration of liver cholesterol and triglyceride also decreased significantly. Plasma, but not liver cholesterol-lowering effect, was roughly comparable with that of cholestyramine. Chitosan at the 10% level further reduced plasma cholesterol, but depressed growth. Also, finer chitosan particles tended to restrain growth even at the 2% level. In rats fed a cholesterol-free diet containing 0.5% chitosan for 81 days, the concentration of serum cholesterol was the same with that of the corresponding control, but relatively more cholesterol existed as high-density lipiproteins and less as very low-density lipoproteins. Dietary chitosan increased fecal excretion of cholesterol, both exogenous and endogenous, while that of bile acids remained unchanged. There was no constipation or diarrhea. A proper supplementation of chitosan to the diet seemed to be effective in lowering plasma cholesterol.

Murine fetal resorption and experimental pre-eclampsia are induced by both excessive Th1 and Th2 activation.

It has been proposed that immune responses in mammalian normal pregnancy are Th2-like, thereby protecting the fetus and placenta from being rejected. Administration of exogenous Th1 cytokines into pregnant mice is reported to induce feto-placental resorption. However, the effects of exogenous Th2 cytokines and Th2 directed responses in pregnant animals have not been well studied. In this study, we examined IL-4 and IL-12, which play decisive roles in the development of Th2 and Th1 responses, respectively, in the induction of fetal resorption and development of experimental pre-eclampsia. Transfer of either IL-4 and/or IL-12 stimulated splenocytes from BALB/C virgin female mice into BALB/C pregnant mice mated with either C57BL/6 or BALB/C male mice resulted in fetal resorption and glomerular nephritis associated with hypertension and proteinuria. In mice treated with IL-12 stimulated splenocytes, fatty liver degeneration associated with bile retention was observed. These results indicate that both excessive Th1 and Th2 activation contribute to the development of fetal resorption and pre-eclampsia, but that Th1 is critical to the development of liver degeneration.

Triacylglycerol lipase mediated release of arachidonic acid for prostaglandin synthesis in rabbit kidney medulla microsomes.

The effect of triarachidonin on the synthesis of prostaglandins in rabbit kidney medulla microsomes was examined. Medulla microsomes were incubated with triarachidonin in 0.1 M--Tris/HCl buffer (pH 7.0) containing reduced glutathione and hydroquinone and the formed prostaglandin E2, prostaglandin F2 alpha and prostaglandin D2 were measured by high-pressure liquid chromatography using 9-anthryldiazomethane for derivatization. The addition of triarachidonin (1-10 microM) stimulated prostaglandin formation in a dose-dependent manner. Under our incubation conditions rabbit kidney medulla was found to produce prostaglandin E2 mainly. When arachidonic acid, instead of triarachidonin, was added to the incubation mixture of microsomes, the identical profile of prostaglandin products was obtained. When the pH of the reaction mixture was changed from 7.0 to 8.0, the rate of triarachidonin-induced prostaglandin E2 formation was approximately 60% of that observed at pH 7.0. Studies utilizing Ca2+ and EGTA revealed that triacylglycerol lipase of kidney medulla is independent of Ca2+. The addition of epinephrine made the stimulatory effect of triarachidonin on prostaglandin E2 formation more pronounced. These results suggest that epinephrine-activated triacylglycerol lipase is present in the renomedullary microsomes, and this enzyme activity is a potential mediator of release of arachidonic acid for prostaglandin synthesis in the kidney medulla.

Hemolysis caused by CMV infection in a pregnant woman with silent elliptocytosis.

Elliptocytosis is reported to occur in at least 1 per 5000 individuals, but most cases are heterozygous and do not show clinical hemolysis. Healthy individuals with silent elliptocytosis, however, may suddenly have an episode of hemolysis [1]. Here we report a woman in the third trimester of pregnancy who suffered from cytomegalovirus (CMV) infection with hemolysis. Scanning electron microscopy showed that half of her red blood cells were oval, and protein analysis revealed a 50% reduction of protein 4.1. We discuss the role of CMV infection and pregnancy in the onset of hemolysis in a patient with otherwise silent elliptocytosis.

Elevation of serum lipid peroxide level associated with doxorubicin toxicity and its amelioration by [dl]-alpha-tocopheryl acetate or coenzyme Q10 in mouse (doxorubicin, toxicity, lipid peroxide, tocopherol, coenzyme Q10).

Elevations of serum lipid peroxide levels were demonstrated in mice after an equitoxic dose of doxorubicin. When BDF1 mice were injected with doxorubicin (20 mg/kg body weight, IP), lipid peroxide levels in sera were elevated 1 day after the injection and the levels declined on subsequent days. 5-Fluorouracil (400 mg/kg body weight, IP) never changed the peroxide levels in serum. Furthermore, it was found that the co-administration of [dl]-alpha-tocopheryl acetate or coenzyme Q10 IM strongly inhibited the doxorubicin-induced elevation of lipid peroxides in serum. The effectiveness of [dl]-alpha-tocopheryl acetate or coenzyme Q10 in reducing the lethality of doxorubicin in mice was also confirmed. These results indicate that the measurement of serum 2-thiobarbituric acid-reacting substances provided a useful measurement of lipid peroxide levels, which may be involved in some way with doxorubicin toxicity, and that the administration of antioxidants provide protection against some of the side effects of doxorubicin.