The risk factors for bleomycin-induced lung injury (BLI), a fatal complication of cancer chemotherapy, are not well-established. The renin-angiotensin-aldosterone system (RAAS) has recently been ...suggested to play a role in the development of lung injury. This study clarified the impact of hypertension (HTN) and the administration of RAAS inhibitors on BLI occurrence in patients treated with bleomycin-containing regimens.
We retrospectively analyzed the data of 190 patients treated with a bleomycin-containing regimen for Hodgkin lymphoma or germ cell tumors at our institutions from 2004 to 2018.
Overall, 190 patients received bleomycin, and symptomatic BLI occurred in 21 (11.1%) cases. In the multivariate analysis, age ≥ 65 years (odd ratio, 10.90; 95% confidence interval, 3.72-32.20; P < .001) and history of HTN (odds ratio, 3.32; 95% confidence interval, 1.07-10.30; P = .04) were found to be significant risk factors for BLI onset. BLI occurred in 3.6% (n = 5) of patients with no risk, 11.8% (n = 2) of those whose only risk factor was HTN, 31.6% (n = 6) of those whose only risk factor was age ≥ 65 years, and 57.1% (n = 8) of those with both risk factors (P < .001). BLI-induced mortality rates in each group were 0.0% (n = 0), 5.9% (n = 1), 10.5% (n = 2), and 42.9% (n = 6) (P < .001), respectively. Among 31 patients with HTN, BLI incidence was 12.5% in patients who were administered RAAS inhibitors and 53.3% in those who were not (P = .02).
Older age and history of HTN were independent risk factors for the development of BLI, and the administration of RAAS inhibitors might reduce the onset of BLI.
•Bleomycin use can lead to BLI, which could be fatal in some cases.•RAAS inhibitors have antihypertensive effects.•Age and a history of HTN were independent risk factors for the development of BLI.•RAAS inhibitors were suggested to suppress the onset of BLI.
This study clarified the impact of hypertension and the administration of renin-angiotensin-aldosterone system inhibitors on the occurrence of bleomycin-induced lung injury (BLI). We retrospectively analyzed the data of 190 patients treated with bleomycin-containing chemotherapy. Age ≥ 65 years and a history of hypertension were significant factors for BLI onset. BLI occurrence was lower in patients who used renin-angiotensin-aldosterone system inhibitors.
Case: The patient was a 55-year-old female. A tumor of the pancreatic tail was found during a medical examination, and a laparoscopic distal pancreatectomy was performed at our hospital. Histological ...examination revealed the diagnosis of a pancreatic neuroendocrine tumor (PanNET) grade 3 (G3) (Ki-67 index: 20-30%). Seven months after the initial surgery, bile duct dilatation and abnormal liver functions〔aspartate aminotransferase (AST): 171U/l, alanine transaminase ALT: 86U/l〕were observed, and upper gastrointestinal endoscopy was performed for further examination, showing a papillary reddish tumor with a white coat protruding from the papilla of Vater. Considering the possibility of local recurrence of PanNET G3, although not typical, the patient underwent a remnant total pancreatectomy. Histologically, immunohistochemical stains were positive for synaptophysin and chromogranin A, and the Ki-67 index was around 30-40%, indicating that this tumor was a recurrence of the PanNET G3. The patient is alive without any recurrence at 24 months after the second surgery.
Japanese larch (
=
) is often characterized by its high growth rate with heterophyllous shoots, but the functional differences of heterophyllous shoots still remain unclear. Recently, abrupt high ...temperature and drought during spring induced high photosynthetic rate via change in leaf morphology of the deciduous habit. In order to reveal the photosynthetic characteristics of both short and long-shoot needles of sunny canopy of the larch trees using a canopy tower, we calculated the seasonal change of gas exchange characters and leaf mass per area (LMA) and foliar nitrogen content (N) of heterophyllous needles: short and long-shoot needles over 3 years. No marked difference in light-saturated photosynthetic rates (P
) was observed between short and long shoots after leaf maturation to yellowing, although the difference was obvious in a specific year, which only shows that seasonal change in temperature and soil moisture determines the in situ photosynthetic capacity of needles. The large annual and seasonal variations in P
in both shoots were found to be mainly determined by climatic variations, while shoot types determined the strategy of their photosynthetic N utilization as well as the stomatal regulation.
Our previous study showed that enhanced carbonyl stress is closely related to schizophrenia. The endogenous secretory receptor for advanced glycation end-products (esRAGE) is a splice variant of the ...AGER gene and is one of the soluble forms of RAGE. esRAGE is considered to be a key molecule for alleviating the burden of carbonyl stress by entrapping advanced glycation end-products (AGEs). In the current study, we conducted genetic association analyses focusing on AGER, in which we compared 212 schizophrenic patients to 214 control subjects. We also compared esRAGE levels among a subgroup of 104 patients and 89 controls and further carried out measurements of total circulating soluble RAGE (sRAGE) in 25 patients and 49 healthy subjects. Although the genetic association study yielded inconclusive results, multiple regression analysis indicated that a specific haplotype composed of rs17846798, rs2071288, and a 63 bp deletion, which were in perfect linkage disequilibrium (r2 = 1), and rs2070600 (Gly82Ser) were significantly associated with a marked decrease in serum esRAGE levels. Furthermore, compared to healthy subjects, schizophrenia showed significantly lower esRAGE (p = 0.007) and sRAGE (p = 0.03) levels, respectively. This is the first study to show that serum esRAGE levels are regulated by a newly identified specific haplotype in AGER and that a subpopulation of schizophrenic patients are more vulnerable to carbonyl stress.
•Specific functional variants in AGER regulate the serum esRAGE levels.•Schizophrenia shows significant decrease of the serum esRAGE and sRAGE levels.•esRAGE levels account for approximately 40% of the total sRAGE levels.
To evaluate the efficacy of angiotensin II receptor blockers (ARBs) for use in the treatment of diabetic nephropathy, we examined the effects of olmesartan medoxomil (olmesartan), an angiotensin II ...type 1 (AT1) specific ARB, on the progression of nephropathy in Zucker diabetic fatty (ZDF) rats, an animal model of type 2 diabetes. We used 2 doses of olmesartan, a sub-antihypertensive dose and an antihypertensive dose, to specifically examine whether the drug exerts beneficial effects on the kidney without lowering blood pressure. Olmesartan mixed in the diet at a concentration of 0.001% (approximately 0.6 mg⁄kg⁄day) or 0.01% (approximately 6 mg⁄kg⁄day) was administered for 19 weeks starting from 12 weeks of age, when the animals developed microalbuminuria. Lean non-diabetic rats served as controls. ZDF rats had hyperglycemia, hyperinsulinemia, and moderate hypertension as compared to lean control rats. Plasma glucose and insulin concentrations were not affected by olmesartan, and blood pressure was lowered only by the high dose of olmesartan. Progressive proteinuria in ZDF rats was greatly (about 70%) suppressed by the high dose of olmesartan and moderately (about 30%) suppressed by the low dose that did not significantly lower blood pressure. ZDF rats exhibited hyperlipidemia and hypoalbuminemia, both of which were substantially corrected by treatment with olmesartan. The histological evidence of glomerular and tubular damage in the ZDF rats was also reduced by the drug. These results indicate that AT1 receptor blockade with olmesartan retards the progression of nephropathy associated with type 2 diabetes without affecting glucose metabolism, and that this renal protective effect is at least partly independent of the antihypertensive effect of the drug. (Hypertens Res 2002; 25: 271-278)
Background: Only a few studies have evaluated the abnormalities of ambulatory blood pressure (ABP) in patients with nephrotic syndrome (NS). Methods: The 24-h ABPs were measured in primary NS ...patients with acute onset of disease and analyzed in relation to the clinical variables. Results: Our subjects comprised 21 patients: 17 with minimal change disease and 4 with focal segmental glomerulosclerosis. Of these patients, 8 (38%) had daytime hypertension, 13 (62%) had nighttime hypertension, and 13 (62%) were non-dippers (nighttime-to-daytime ratio of ABP: NDR > 0.9). The serum sodium level was correlated with the average 24-h ABP and NDR, after adjustment for other clinical variables, such as the increase in body weight, serum albumin level, and urinary protein excretion. The data from repeated ABP measurements, before and after the achievement of remission, showed a marked decrease in the average 24-h ABP after remission. Furthermore, change in the serum sodium level was significantly correlated with the change in NDR. Conclusion: These results suggest that alteration in renal handling of sodium and water, which might be reflected in serum sodium level, is involved in the abnormality of circadian blood pressure in primary NS patients.
Abstract
Statistical fine-mapping prioritizes putative causal variants from a large number of candidate variants, and is widely used in expression quantitative loci (eQTLs) studies. In eQTL ...fine-mapping, the existence of causal variants for gene expression is not guaranteed, since the genetic heritability of gene expression explained by nearby (cis-) variants is limited. Here we introduce a refined fine-mapping algorithm, named Knockoff–Finemap combination (KFc). KFc estimates the probability that the causal variant(s) exist in the cis-window of a gene through construction of knockoff genotypes (i.e. a set of synthetic genotypes that resembles the original genotypes), and uses it to adjust the posterior inclusion probabilities (PIPs). Utilizing simulated gene expression data, we show that KFc results in calibrated PIP distribution with improved precision. When applied to gene expression data of 465 genotyped samples from the Japan COVID-19 Task Force (JCTF), KFc resulted in significant enrichment of a functional score as well as reporter assay hits in the top PIP bins. When combined with functional priors derived from an external fine-mapping study (GTEx), KFc resulted in a significantly higher proportion of hematopoietic trait putative causal variants in the top PIP bins. Our work presents improvements in the precision of a major fine-mapping algorithm.
Adsorption-driven molecular recognitive photocatalytic decomposition of organic molecules in aqueous mixtures was achieved on TiO
2/nanoporous silica core/shell particles with controlled pore ...diameters.
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► Nanoporous silica coating to impart molecular selective photocatalytic ability to TiO2 particle. ► P25 core/nanoporous silica shell particles with different size and silanol density of the pores. ► The hybrid materials exhibit molecular recognitive adsorption and photocatalysis.
The coating of TiO
2 particles (P25) by a nanoporous silica layer was conducted to impart molecular recognitive photocatalytic ability. TiO
2/nanoporous silica core/shell particles with varied pore diameters of the shell were synthesized by the reaction of P25 with an aqueous mixture of tetraethoxysilane and alkyltrimethylammonium chloride with varied alkyl chain lengths, followed by calcination. The TEM and nitrogen adsorption/desorption isotherms of the products showed that a nanoporous silica shell with a thickness of ca. 2
nm and controlled pore diameter (1.2, 1.6, and 2.7
nm) was deposited on the titania particle when surfactants with different alkyl chain lengths (C12, C16 and C22) were used. The water vapor adsorption/desorption isotherms of the core/shell particles revealed that a larger amount of water adsorbed on the core/shell particles when the pore diameter is larger. The
29Si MAS NMR spectra of the core/shell particles showed that the amount of surface silanol groups was independent of the water vapor adsorption capacity of the products. The possible molecular recognitive photocatalysis on the products was investigated under UV irradiation using two kinds of aqueous mixtures containing different organic compounds with varied sizes and functional groups: a 4-butylphenol, 4-hexylphenol, and 4-nonylphenol mixture and a 2-nitrophenol, 2-nitro-4-phenylphenol, and 4-nitro-2,6-diphenylphenol mixture. It was found that the core/shell particles exhibited selective adsorption-driven molecular recognitive photocatalytic decomposition of 4-nonylphenol and 2-nitrophenol in the two mixtures.
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