Introduction of a diverse genetic background of Pyrus into Malus through intergeneric hybridization.

Wide hybridizations across species and genera have been employed to enhance agriculturally important traits in crops. Within the tribe Maleae of the Rosaceae family, different genera and species exhibit several traits useful for increasing diversity and gene pool through hybridization. This study aimed to develop and characterize intergeneric hybrid individuals between Malus and Pyrus. Through seed germination, shoot multiplication, and rooting in vitro, acclimatized seedlings showing vegetative growth on their own roots were obtained from crosses of Malus × domestica pollinated by Pyrus communis, P. bretschneideri, and the Pyrus interspecific hybrid (P. communis × P. pyrifolia). Comparative analysis of leaf morphology, flow cytometry, and molecular genotyping confirmed the hybrid status of the individuals. Genome-wide genotyping revealed that all the hybrid individuals inherited genomic fragments symmetrically from the Malus and Pyrus parents. To the best of our knowledge, this is the first report on the development of intergeneric hybrid seedlings between Malus × domestica and P. bretschneideri. Furthermore, the Pyrus interspecific hybrid individual served as a bridge plant for introducing the genetic background of P. pyrifolia into Malus × domestica. The results of this study provided a crucial foundation for breeding through intergeneric hybridization between Malus and Pyrus, facilitating the incorporation of valuable traits from diverse gene pools.

Can institutions foster cooperation by wealth redistribution?

Theoretical models prescribe how institutions can promote cooperation in a population by imposing appropriate punishments or rewards on individuals. However, many real-world institutions are not sophisticated or responsive enough to ensure cooperation by calibrating their policies. Or, worse yet, an institution might selfishly exploit the population it governs for its own benefit. Here, we study the evolution of cooperation in the presence of an institution that is autonomous, in the sense that it has its own interests that may or may not align with those of the population. The institution imposes a tax on the population and redistributes a portion of the tax revenue to cooperators, withholding the remaining revenue for itself. The institution adjusts its rates of taxation and redistribution to optimize its own long-term, discounted utility. We consider three types of institutions with different goals, embodied in their utility functions. We show that a prosocial institution, whose goal is to maximize the average payoff of the population, can indeed promote cooperation-but only if it is sufficiently forward-looking. On the other hand, an institution that seeks to maximize welfare among cooperators alone will successfully promote collective cooperation even if it is myopic. Remarkably, even a selfish institution, which seeks to maximize the revenue it withholds for itself, can nonetheless promote cooperation. The average payoff of the population increases when a selfish institution is more forward-looking, so that a population under a selfish regime can sometimes fare better than under anarchy. Our analysis highlights the potential benefits of institutional wealth redistribution, even when an institution does not share the interests of the population it governs.

Serum 25-hydroxyvitamin D3 Levels and Diabetes in a Japanese Population: The DOSANCO Health Study.

BACKGROUND: Both decreased insulin sensitivity and impaired insulin secretion are common in Asian populations with diabetes, in contrast to Western populations. There is limited evidence regarding the association between insulin response in diabetes in Asian populations and serum 25-hydroxyvitamin D3 (25[OH]D3) insufficiency. METHODS: The present cross-sectional study compared the prevalence of diabetes, defined as a fasting plasma glucose level ≥126 mg/dL and/or a HbA1c level ≥6.5%, among 480 participants aged 35-79 years not taking anti-diabetes medications, based on serum 25(OH)D3 levels. A logistic regression model was used to calculate the odds ratios for diabetes in each serum 25(OH)D3 group. Furthermore, this study examined the association between serum 25(OH)D3 levels and the index of homeostasis model assessment of insulin resistance (HOMA-IR) using a linear regression model. RESULTS: The prevalence of diabetes was 7.29% in the study population, and was higher in lower serum 25(OH)D3 quartile groups. The odds ratios for diabetes in the first, second, and third serum 25(OH)D3 quartile groups (25[OH]D3: ≤18.10, 18.11-22.90, and 22.91-28.17 ng/mL) were 4.02 (95% confidence interval [CI], 1.25-12.92), 2.50 (95% CI, 0.77-8.10), and 1.91 (95% CI, 0.60-6.09), respectively, with the fourth quartile group (⩾28.18 ng/mL) serving as the reference group, after adjusting for sociodemographic, lifestyle, physical and environmental factors. Serum 25(OH)D3 levels showed an inverse association with log-transformed HOMA-IR after adjusting for similar factors (standardized ß = -0.08; 95% CI, -0.14 to -0.02). CONCLUSION: Serum 25(OH)D3 levels were inversely associated with diabetes prevalence in a general Japanese population, with a slight inverse association between serum 25(OH)D3 levels and HOMA-IR.

Serum 25-hydroxyvitamin D3 levels and poor sleep quality in a Japanese population: the DOSANCO Health Study.

OBJECTIVE: The present cross-sectional study investigated the relationship between serum 25-hydroxyvitamin D3 (25[OH]D3) levels and the presence of poor sleep quality in a community-based Japanese adult population. METHODS: Poor sleep quality, defined as poor subjective sleep quality and/or use of sleep medications, was assessed using a self-administered questionnaire. The prevalence of poor sleep quality was compared among 512 Japanese participants aged 35-79 years, based on serum 25(OH)D3 levels, which were determined using tandem mass spectrometry. A logistic regression model was used to calculate the odds ratios (ORs) for the presence of poor sleep quality in each group with the highest quartile of 25(OH)D3 serving as the reference group. RESULTS: Poor sleep quality was reported by 33.2% of the total study population. The prevalence of poor sleep quality was higher in the first quartile group (25[OH]D3: 2.08-18.13 ng/mL) than in the second, third and fourth quartile groups (18.14-23.07 ng/mL, 23.08-28.32 ng/mL, and 28.33-78.83 ng/mL, respectively). The ORs for poor sleep quality were 1.86 (95% confidence interval, 1.08-3.20) for the first quartile group, 0.73 (0.41-1.29) for the second quartile group, and 0.73 (0.42-1.27) for the third quartile group after adjusting for age, sex, and sociodemographic, lifestyle, physical and environmental factors, while the ORs were 1.68 (0.96-2.95), 0.69 (0.39-1.24), and 0.65 (0.37-1.15) after further adjustment for overall health status and depression status. CONCLUSIONS: The first quartile group of serum 25(OH)D3 was associated with the presence of poor sleep quality.

Determination of Serum 25-Hydroxyvitamin D3 by LC/MS/MS and Its Monthly Variation in Sapporo Indoor Workers.

25-Hydroxyvitamin D3 (25(OH)D3) as the metabolite of vitamin D, is connected with various of diseases, and important to people with limited sunshine. Thus, the investigation of serum 25-hydroxyvitamin D and its variation in these people is necessary. In this study, a simple, precise, and accurate method for serum 25(OH)D3 determination by LC/MS/MS was developed. Serum samples were obtained monthly for one year from 11 male and 11 female indoor workers in Sapporo, Japan, and the overall 25(OH)D3 concentration was 12.9 ± 4.7 ng/mL. The 25(OH)D3 in females was significantly lower than that in males (14.0 ± 5.0 vs. 11.9 ± 4.3 ng/mL). The serum 25(OH)D3 concentration in males and females were both strongly correlated to UV-B radiation (r2 = 0.8477 and 0.7384, respectively), with a two-month's lag. Also the monthly change in 25(OH)D3 in males was more significant than that in females.

Microwave-assisted Derivatization of Fatty Acids for Its Measurement in Milk Using High-Performance Liquid Chromatography.

Fatty acid (FA) profiling of milk has important applications in human health and nutrition. Conventional methods for the saponification and derivatization of FA are time-consuming and laborious. We aimed to develop a simple, rapid, and economical method for the determination of FA in milk. We applied a beneficial approach of microwave-assisted saponification (MAS) of milk fats and microwave-assisted derivatization (MAD) of FA to its hydrazides, integrated with HPLC-based analysis. The optimal conditions for MAS and MAD were determined. Microwave irradiation significantly reduced the sample preparation time from 80 min in the conventional method to less than 3 min. We used three internal standards for the measurement of short-, medium- and long-chain FA. The proposed method showed satisfactory analytical sensitivity, recovery and reproducibility. There was a significant correlation in the milk FA concentrations between the proposed and conventional methods. Being quick, economic, and convenient, the proposed method for the milk FA measurement can be substitute for the convention method.

Mass Spectrometric Quantification of Amphipathic, Polyphenolic Antioxidant of the Pacific Oyster (Crassostrea gigas).

A novel amphipathic phenolic compound, 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), that can be isolated from the Pacific oyster (Crassostrea gigas) has been found to protect human hepatocytes against oxidative stress. This study aims to establish a method for the measurement of DHMBA for industrial application. Liquid chromatography-tandem mass spectrometry using deuterated DHMBA as an internal standard and a polar end-capped ODS (Hypersil GOLD aQ) as the solid phase was validated. The limit of detection was 0.04 pmol (S/N = 5), and the limit of quantitation was 0.1 pmol (S/N = 10). The calibration curve was linear throughout the range of 0.1 - 16 pmol (r(2) = 0.9995). This method successfully quantified DHMBA in oysters from 11 sea areas in Japan. The results showed that the yield of DHMBA was variable from 9.8 to 58.8 µg g(-1) whole oyster meat wet weight but not affected by the seawater temperature. The proposed LC-MS/MS method is useful in quantitative studies for DHMBA and potentially for other amphipathic substances.

Anti-apoptotic effects of novel phenolic antioxidant isolated from the Pacific oyster (Crassostrea gigas) on cultured human hepatocytes under oxidative stress.

The antioxidant, and hepatoprotective properties of 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), a natural phenolic antioxidant isolated from the Pacific oyster, were defined using cultured human hepatocyte-derived cells (C3A). DHMBA showed no cytotoxicity at 62.5-500µM, as well as chlorogenic acid (CGA), vitamin C, and vitamin E. However, butylated hydroxytoluene, eicosapentaenoic acid, docosahexaenoic acid and catechin reduced cell viability. In the presence of the prooxidant 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH), DHMBA at 125-500µM improved cell viability, whereas CGA had no effect. DNA ladder formation and flow-cytometric studies indicated that DHMBA inhibited AAPH-induced apoptosis and necrosis. CGA was ineffective. Thus, DHMBA is a novel, potent antioxidant, effectively protecting cultured hepatocytes from apoptosis and necrosis caused by oxidative stress. Additionally, the concentration of DHMBA was determined by mass spectrometry to be 24.4µmol/kg wet oyster meat, and three polyphenols (gentisic acid, daidzein, and matairesinol) were newly identified in the oyster extracts.

[Pre-analytical problems on assay conditions for blood midkine].

We have established the assay conditions of midkine (MK) measurement, the reference intervals and evaluation for clinical significance of blood MK measurement. MK is a kind of cytokines and basic protein which is a heparin-binding growth factor of various cells. The increase of MK expression suggests a prognostic value in early stage on cancers or inflammation. But significant problems in the MK measurement are alterations resulting from standing time and temperature instability after blood collection. Assay of MK was performed with solid phase human MK immunoassay recently developed sensitive enzyme linked immunosorbent method. The assay condition of MK was required to be separated immediately after blood sampling within 24 hrs at 4 degrees C or within 2 hrs at room temperature-standing. Plasma sample obtained with EDTA-2Na or citric acid-Na, and serum obtained from plain tube container showed good results. Linearity was obtained up to 1500 pg/ml and repeatability and reproducibility were within 10% as CV%. The recovery of MK was 101.1+/-3.8% with 10 specimens ranged 97-105%. Addition of interfering substances showed no effect on assay results when hemoglobin, EDTA-Na, citrate and turbidity check, but conjugated bilirubin (over 0.68 mmol/l) and gave negative errors within 10% in the assay results and heparin gave negative errors. The reference interval was 550 +/- 160 pg/ml in healthy individuals serum.

Inhibition of lipopolysaccharide-induced tissue factor expression in monocytes by urinary trypsin inhibitor in vitro and in vivo.

Tissue factor (TF) plays a critical role in the pathogenesis of disseminated intravascular coagulation (DIC) observed in patients with septic shock. Urinary trypsin inhibitor (UTI), a multivalent protease inhibitor, is currently used for treatment of patients with septic shock. This study was undertaken to determine whether UTI reduces LPS-induced coagulation abnormalities by inhibiting lipopolysaccharide (LPS)-induced expression of TF by monocytes. UTI inhibited LPS-induced increases in both TF activities and TF mRNA expression in monocytes without affecting the viability. Although activation of nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1) and extracellular signal-regulated kinase (ERK)1/2 were shown to be critically involved in LPS-induced increases in TF activities in isolated monocytes, UTI inhibited phosphorylation of ERK1/2 and decreased expression of early growth response factor-1 (Egr-1) induced by LPS without affecting the activation of NF-kappaB and AP-1. UTI inhibited both the expression of TF mRNA in whole blood, increases in TF activities in mononuclear cells, and increases in serum levels of fibrin and fibrinogen degradation products (E) in rats given LPS without affecting the number of monocytes in the peripheral blood. Taken together these results strongly suggested that UTI might reduce LPS-induced coagulation abnormalities in rats by inhibiting TF expression in monocytes through inhibition of Egr-1 expression.

Role of extracellular superoxide dismutase in patients under maintenance hemodialysis.

BACKGROUND: It has been well documented that free radical injury is involved in the progression of chronic renal failure. Extracellular superoxide dismutase (EC-SOD), localized on the endothelial cell surface, plays an important role in reducing oxidative stress especially in the vessels by binding to the endothelial cell surface via the heparin-binding domain. Although EC-SOD Arg213Gly, which cannot bind on endothelial cells, has been considered a polymorphism, the effect of EC-SOD on hemodialysis patients has not been well examined. METHODS: In 178 hemodialysis patients, the following examinations were performed. EC-SOD Arg213Gly was examined by polymerase chain reaction (PCR)-induced mutation restriction analysis (PCR-IMRA). As indexes of atherosclerosis, the annual progression in intima-media thickness (DeltaIMT), plaque score, pulse wave velocity (PWV) and plasma-oxidized low-density lipoprotein (OxLDL) values were examined. RESULTS: PCR-IMRA revealed that 20 of 178 patients possessed the mutation (11.2%), and the incidence was about twice as high as that in a previously reported Japanese population. Although there were no statistical differences in plaque score and PWV with and without EC-SOD Arg213Gly, DeltaIMT and plasma OxLDL values in patients with EC-SOD Arg213Gly were significantly higher than those in patients without the mutation. CONCLUSION: EC-SOD Arg213Gly is an accelerating factor for the progression of renal failure and atherosclerosis.

Measurement of total and differential white blood cell counts in synovial fluid by means of an automated hematology analyzer.

We developed a rapid and accurate method for quantifying total and differential white blood cell (WBC) counts by pretreating synovial fluid with hyaluronidase and using an automated hematology analyzer. Forty-seven samples of synovial fluid that had been placed in blood-collection tubes containing ethylenediamine- N,N,N',N' -tetraacetic acid as an anticoagulant were treated with hyaluronidase at 37 degrees C for 10 minutes, and then the total and differential WBC counts were determined by means of the automated hematology analyzer. Results were compared with those achieved by traditional manual counting methods. For the automated method, the coefficient of variation values for within-run precision of the WBC count were 5.27%, 3.56%, and 3.01% at 0.54, 1.12, and 2.05 x 10(9) /L, respectively; the run-to-run coefficient of variation values was less than 10.0%. The total and differential WBC counts obtained by this automated method showed good correlation with those obtained by the hemocytometer method ( r = .998; P < .0001; regression formula, y = 0.986 x - 0.072). Bland-Altman plots indicated no significant discrepancy between the methods. Our evaluation supports the use of this automated hematology analyzer method to measure total and differential WBC counts, which should aid clinical diagnosis.

[Pitfalls in homogeneous assays for HDL-c and LDL-c in serum].

Between 1994 and 2004, homogenous assays for HDL-C and LDL-C based on different determination principles were developed to replace complicated conventional precipitation methods. Nowadays, most laboratories employ homogenous assays. However, due to differences in principles and reactivity, measurements made by different assays do not necessarily match in some cases. HDL-C determinations may vary depending on duration and conditions of serum storage for the CDC-DCM and the homogenous assay methods, due to their different principles of determination. In patients with cholestasis, apoE-rich HDL, Lp-X and Lp-Y are occasionally observed. In these cases, the reactivity of homogenous assays for HDL-C varies markedly among the manufacturers. Furthermore, because the specific gravities of Lp-X and Lp-Y are comparable to that of LDL, these lipoproteins are grouped as LDL by ultracentrifugation, and this is a source of confusion in clinical settings. The American CDC assesses the accuracy of cholesterol assays by the BQ method, which measures the total of IDL, the narrowly-defined LDL, and Lp(a). However, of the various homogenous assays for LDL-C, reactivities to IDL and Lp (a) differ, and as a result, it is possible that type III hyperlipidemia characterized by increased IDL may be misdiagnosed.

[My Kumamoto life of 19 years].

In this paper titled "My Kumamoto Life of 19 Years; The Travel for Times", the memorial lecture on my retirement from Kumamoto National University Corporation Integrated Medical and Pharmaceutical Sciences, Department of Biomedical Informatics (Chairman) is summarized. As they say "Time flies", time extends from seconds to years. The lecture includes a summary of my short term research and long term studies, such as age-dependant and gene-related changes in ageing over 5 or more years in the healthy elderly. Short-term study mostly involved of newly evaluated assay methods for important substances such as the second level in the cell life span in the variation of lipid metabolite of cardiovascular diseases based on atherosclerosis, Alzheimer disease, and their evaluation by homogeneous assay of HDL-C, LDL-C, enzymatic assay for choline relating metabolites, and lipoperoxide as the results of free radical reactions. The intermediate-term studies were mainly on the development of total laboratory automation (TLA) for the management of the laboratory of the university hospital. The hospital has various degrees of sophistication in its laboratory services. Technicians were allowed to transport specimens immediately by using an air-shooter system after drawing blood, from the emergency room to the central laboratory. Routine specimens could be measured within 30 min and the results could be automatically sent to the physician's office. It greatly minimized reporting errors, decreased the exposure to biohazards, reduced labor expense, improved operation efficiency, and shortened turnaround time. Moreover, for the outpatients and emergency laboratories, we constructed a robotic measuring system which was assembled into a sequential method for the analysis of chemistry, hematology and urinalysis specimens by using a polyarticular robot. The robot arm extends to a bar-coded tube, picking up and placing test tubes on a turn table of autoanalyzers for analysis without manpower. This is the first known effective unmanned procedure for assay in the world of laboratory medicine. Also, our research on pathological informatics was begun. Our laboratory had 7 themes; the study of the reference intervals in the elderly as one of strategy of standardization on laboratory data (Drs. Uji Y, Sugiuchi H), the study of the activation mechanism of ribosomal proteins by the functions of blood cells (Drs. Shibuya Y, Senba U), the evaluation of diagnostic methods in latent ailments by gene analysis (Dr. Ando Y), the evaluation of a highly sensitive method for disseminated intravascular coagulopathy (Okajima K), the study of the neogenesis of blood vessels by physical invasion (Uchiba M), the study of the deposition mechanism of amyloid proteins and evaluation of the diagnostic methods in the autonomic system(Drs. Ando Y, Nakamura M), and the study of the function of blood stem cells in blood transfusion services (Drs. Yamaguchi K, Yonemura M, Tsunemi M). Finally, my long term work also included research into the early diagnosis and prediction of latent ailments and the variation of serum proteins levels in the healthy aged. The conclusion was that the reference value of healthy populations and individuals (intra-personal) who had no combined ailments, in follow-up for 5 years, categorized by age, sex, and social conditions, gave a narrower range of variation than did large mixed populations (inter-personal), in laboratory tests and activity of daily living (ADL). Concerning the early diagnosis and prediction studies for the latent ailments in the aged, variations of serum protein levels in the healthy aged were classified into 3 types: serum proteins levels increased with advancing age (alphaAT, mainly acute phase reactant proteins), those that decreased with advancing age (albumin mainly transporting proteins) and proteins with no significant variation. The higher increase of the alpha1AT/beta2 III ratio in the healthy aged over 60 years old is suspected to create symptoms in the near future. The papers presented concerning ageing studies were presented at the APCCC Symposium (India, 2002) and the IFCC Symposium (Kyoto, 2002), and the TLA study was also presented at the Symposium of XX World Congress of Pathology and Laboratory Medicine (San Paulo Brazil 1999).

Urinary trypsin inhibitor reduces LPS-induced hypotension by suppressing tumor necrosis factor-alpha production through inhibition of Egr-1 expression.

Although urinary trypsin inhibitor (UTI) has been shown to inhibit tumor necrosis factor (TNF)-alpha- production, the detailed mechanism(s) remains unclear. This study was undertaken to elucidate the molecular mechanism(s) underlying this inhibitory effect in monocytes in vitro and in rats given lipopolysaccharide (LPS). TNF-alpha production by monocytes stimulated with LPS (100 ng/ml) was inhibited by UTI at concentrations higher than 100 U/ml. Expression of early growth response factor-1 (Egr-1) and phosphorylation of extracellular signal-regulated protein kinases 1/2 in monocytes stimulated with LPS were inhibited by UTI. UTI (50,000 U/kg i.v.) inhibited LPS (5 mg/kg i.v.)-induced increases in lung tissue levels of Egr-1, TNF-alpha mRNA, and TNF-alpha in rats. UTI inhibited LPS-induced hypotension by inhibiting pulmonary induction of inducible nitric oxide synthase (iNOS). We previously demonstrated that anti-TNF-alpha antibody and aminoguanidine, a selective inhibitor of iNOS, reduced LPS-induced hypotension in this animal model. Furthermore, we also reported that reduction of LPS-induced coagulation abnormalities in rats did not affect inflammatory responses and hypotension in this animal model. Taken together, these observations strongly suggested that UTI inhibited LPS-induced production of TNF-alpha by inhibiting activation of the extracellular signal-regulated protein kinases 1/2-Egr-1 pathway in monocytes, which might at least partly contribute to reduction of hypotension through inhibition of iNOS induction in rats given LPS.

Primary structures of guinea pig high- and low-molecular-weight kininogens.

Guinea pig high-molecular-weight and low-molecular-weight (HMW and LMW) kininogen cDNA were amplified from liver mRNA by RT-PCR. Their nucleotide sequences were analyzed and deduced to amino acid sequences. The HMW kininogen, composed of 607 amino acid residues with a 18-residue signal sequence, possessed the cysteine protease inhibitor domains I and II, the bradykinin domain, the histidine-rich region, and the prekallikrein-binding region. The amino acid sequence preceding the bradykinin domain was found not to be -Leu-Met-Lys- but -Leu-Thr-Arg-. Therefore, kallidin (Lys-bradykinin) and Met-kallidin are not liberated from the guinea pig kininogens. We purified the HMW kininogen protein from plasma and prepared the kinin-free form using guinea pig plasma kallikrein. Although the amino-terminal of the HMW kininogen was modified, the 25 amino-terminal residues of the light chain of the kinin-free kininogen corresponded to the deduced sequence just after the bradykinin moiety of the HMW kininogen. With regard to the LMW kininogen, the nucleotide sequence down to T(1200) as well as the amino acid sequence till Thr(382) was identical to that of the HMW kininogen. We also examined the localization of the guinea pig kininogen gene on the prometaphase lymphocyte chromosomes by fluorescence in situ hybridization method. Two pair signals were observed on a pair of homologous chromosomes, each of which is composed of two chromatids. Based on these findings, we concluded that HMW and LMW kininogens are produced from the single kininogen gene in guinea pig as in the cases of the other mammalian species reported so far.

A different amyloid formation mechanism: de novo oculoleptomeningeal amyloid deposits after liver transplantation.

BACKGROUND: Liver transplantation has served as a treatment for patients with familial amyloidotic polyneuropathy (FAP) because variant transthyretin (TTR), the pathogenic protein of FAP, is predominantly produced by the liver. However, the effect on amyloid formation of TTR that is synthesised by the retina and the choroid plexus remains to be elucidated in FAP patients with liver transplants. OBJECTIVE: To investigate changes in ocular tissues and the central nervous system (CNS) of FAP patients after liver transplantation. DESIGN: Clinical study. SETTING: Graduate School of Medical Sciences, Kumamoto University, Japan. INTERVENTION: Transplantation of livers from cadaveric or living donors. MEASUREMENTS: Preoperative measures and postoperative (16-108 months) follow-up of clinical data, including routine ophthalmologic, neurologic, and laboratory evaluations. RESULTS: In 22 patients with FAP related to the amyloidogenic TTR (ATTR) Val30Met and 3 patients with FAP ATTR Tyr114Cys, after liver transplantation, 3 patients began to show evidence of de novo glaucoma, and 1 had vitreous opacity that was caused by the variant TTR. Another three patients showed new amyloid deposits in the pupillary margin, which could lead to glaucoma and vitreous opacity. As for changes in the CNS and levels of total protein and TTR in cerebrospinal fluid (CSF), after liver transplantation, two FAP ATTR Tyr114Cys patients exhibited de novo amyloid deposition in the leptomeninges, and total protein and TTR levels in CSF were significantly increased. CONCLUSIONS: Oculoleptomeningeal involvement in FAP was not prevented by liver transplantation because variant TTR produced by the retina and the choroid plexus forms amyloid fibrils in situ.