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Biomedical subjects

Yukio Ando

Publications and source records attributed to Yukio Ando.

At least 37 records · Page 2Linked to original sources
PubMed2005

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.

Adult↗
PubMed2005

Transthyretin-related familial amyloidotic polyneuropathy.

Transthyretin-related familial amyloidotic polyneuropathy (FAP) is a fatal hereditary amyloidosis. Until 20 years ago, FAP was thought to be restricted to endemic occurrence in certain areas. However, owing to progress in biochemical and molecular genetic analyses, FAP is now believed to occur worldwide. As of today, reports of about 100 different points of single or double mutations, or a deletion in the transthyretin gene, have been published, and several different phenotypes of FAP have been documented, even for the same mutation in the transthyretin gene. We present herein the current clinicopathological, biochemical, molecular genetic, and epidemiological aspects of transthyretin-related FAP, and we introduce a new diagnostic procedure for the disease.

Amyloid Neuropathies, Familial↗
PubMed2005

Muscular amyloid angiopathy with amyloidgenic transthyretin Ser50Ile and Tyr114Cys.

Among patients with familial amyloid polyneuropathy (FAP), those with transthyretin Val30Met mainly show distally predominant weakness and atrophy, whereas some FAP patients, including those with transthyretin Ser50Ile and Tyr114Cys, show muscle weakness and atrophy that is dominant proximally, simulating myopathy. To clarify the cause of proximally dominant muscular atrophy in patients with FAP transthyretin Ser50Ile and Tyr114Cys, we investigated the distinctive features of muscle specimens of patients with FAP, 3 of who had Val30Met, 2 Ser50Ile, and 2 Tyr114Cys transthyretin. All specimens showed transthyretin amyloid around blood vessels and perimysium, and neurogenic denervation patterns. The amount of amyloid around the vessels was much greater in patients with FAP Ser50Ile and Tyr114Cys than in Val30Met patients. Muscular amyloid angiopathy may contribute to motor nerve injury that, in turn, may lead to amyotropic changes in patients with FAP Ser50Ile and Tyr114Cys.

Adult↗
PubMed2005

Liver transplantation and new therapeutic approaches for familial amyloidotic polyneuropathy (FAP).

Liver transplantation has been considered as a promising therapy to halt the progression of clinical symptoms in familial amyloidotic polyneuropathy (FAP) because most transthyretin (TTR) is produced by the liver. In addition, domino liver transplantation using an FAP patient's liver has been performed because of a shortage of donor livers. However, because the use of liver transplantation as therapy for FAP has given rise to several problems, an alternative treatment is needed. We have tried several other approaches. Recent studies suggested that certain metal ions affect amyloidogenesis. Among metal ions tested in an in vitro amyloid formation study, Cr3+ increased stability of both normal and mutant TTR tetramers and suppressed TTR amyloidogenesis induced by low pH. Our findings indicate that Cr3+ acts to suppress TTR amyloidogenesis. BSB, a Congo red derivative that binds to amyloid fibrils in FAP as well as to those in senile plaques in Alzheimer's disease, effectively suppressed TTR amyloid formation in vitro. BSB may thus be useful for preventing amyloid formation. Free radical scavenger therapy was also tried in FAP patients but yielded no conclusive results. Immunization for transgenic mice having the ATTR V30M gene using ATTR Y78P resulted in suppression of amyloid deposits. Finally, an RNA/DNA chimera and single-stranded oligonucleotides (SSOs) were tested in vitro and in vivo in an attempt to repair the amyloidogenic TTR gene in the liver and retina. On the basis of results achieved so far, SSO is a promising tool for gene therapy.

Amyloid↗
PubMed2005

Transthyretin synthesis in rabbit ciliary pigment epithelium.

Ocular symptoms of transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP) suggest that ciliary pigment epithelium (CPE) may synthesize TTR and its TTR may lead to amyloid formation in addition to TTR from vessels and retinal pigment epithelium (RPE). To clarify sites of TTR synthesis in ocular tissues, we performed in situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR) for qualitative detection of TTR mRNA. In addition, we quantified levels of TTR mRNA expression by means of real-time quantitative RT-PCR. Furthermore, although TTR is an anti-acute phase protein in serum level, no reports on changes in TTR expression in ocular tissues during acute inflammation exist. To investigate changes in TTR expression in ocular tissues during inflammation, we induced uveitis by endotoxin challenge in rabbits and used real-time quantitative RT-PCR to examine changes in TTR mRNA expression in ocular tissues. In situ hybridization and RT-PCR qualitatively demonstrated TTR mRNA not only in RPE but also in CPE. Real-time quantitative RT-PCR showed that the level of TTR mRNA expression in the CPE was about one-third of that in the RPE. TTR mRNA expression in ocular tissues decreased as the degree of inflammation increased. These results suggest that TTR synthesized in the CPE may lead to ocular manifestations, especially glaucoma, in FAP. TTR mRNA also acts as an anti-acute phase reactant in ocular tissues.

Animals↗
PubMed2005

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.

Arthritis, Infectious↗
PubMed2005

Biochemical characteristics of variant transthyretins causing hereditary leptomeningeal amyloidosis.

Transthyretin (TTR) is a tetrameric protein that can dissociate into amyloidogenic monomers and cause TTR-related amyloidosis. A rare phenotype, called hereditary leptomeningeal TTR amyloidosis, in which TTR amyloid deposition occurs mainly in leptomeninges and subarachnoid vessels, has been reported in patients with several different TTR variants. In the present study, we examined TTR variants immunoprecipitated from the serum and cerebrospinal fluid (CSF) of patients with hereditary leptomeningeal TTR amyloidosis using matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (IP-Mass method). The leptomeningeal-type TTR variants were not detected in the serum but were found at low levels in the CSF. The undetectable levels of the leptomeningeal-type TTR variants in serum could explain the minute amounts of systemic deposition of these variants. The relatively high level of unstable TTR variants in CSF, probably due to increased secretion from the choroid plexus, is considered to be the pathogenesis of the leptomeningeal-type of TTR amyloidosis.

Adult↗
PubMed2005

Studies on unfolded beta-microglobulin at C-terminal in dialysis-related amyloidosis.

BACKGROUND: In 1997, Stoppini et al reported that monoclonal antibody specific to the C-terminal 92-99 of beta(2)-microglobulin (beta(2)m) had been capable of inhibiting fibrillogenesis of beta(2)m in vitro. Meanwhile, recent studies have indicated that an acidifying procedure can unfold conformation of the precursor protein, leading to fibril formation of beta(2)m as well as a transthyretin. METHODS: We thus prepared monoclonal antibody specific to the C-terminal 92-99 (mAb 92-99), and investigated its reactivity in plasma ultrafiltrate and amyloid tissues from 18 hemodialysis patients with dialysis-related amyloidosis (DRA). RESULTS: beta(2)m extracted from ultrafiltrate showed no reaction for mAb 92-99, whereas acidified beta(2)m from ultrafiltrate showed a reaction for mAb 92-99. Similarly, a homogenate of carpal amyloid tissues showed a strong reaction for mAb 92-99 on immunoblotting. Immunohistochemical study showed also a distinct staining for mAb 92-99 in 7 Congophilic specimens from DRA patients. More interestingly, staining for mAb 92-99 could be found in most, though not all, non-Congophilic tissues. CONCLUSION: This study demonstrates that the monoclonal antibody specific to the C-terminal 92-99 of beta(2)m can detect the conformational intermediate in amyloidogenesis of beta(2)m ex vivo, and demonstrates that an unfolded beta(2)m at C-terminal could be found not only in Congophilic area but even in non-Congophilic area as well.

Adult↗
PubMed2005

Ten years of experience with liver transplantation for familial amyloid polyneuropathy in Japan: outcomes of living donor liver transplantations.

OBJECTIVE: We summarize 10 years of experience with liver transplantation for FAP patients in Japan and review the current opinions regarding this treatment for FAP. METHODS AND PATIENTS: All basic report data on patients at the time of transplantation were registered with the Japanese Liver Transplantation Society (JLTS). Based on the JLST report data, more detailed information on FAP patients was requested from each center. RESULTS: Living donor liver transplantation (LDLT) for FAP patients was first performed in Japan in 1993. LDLT has since been performed in 41 FAP patients, including nine cases of temporary auxiliary partial orthotopic liver transplantation (APOLT). Orthotopic liver transplantation (OLT) from cadaveric donors for FAP patients began in 1999, but only one FAP patient has subsequently undergone this procedure. Of these total of 43 FAP patients, 36 are currently alive: the one-year survival rate of patients after transplantation was 93%, and the five-year survival rate of these cases was 77%. Preoperative clinical severity and the nutritional status of patients are correlated with their outcome after liver transplantation. Domino (sequential) liver transplantation has been carried out in 20 domino recipients with end-stage liver diseases. Of the 20 domino recipients, 12 are currently alive. CONCLUSION: For FAP patients, these outcomes after the operation were very similar to those of OLT from cadaveric donors reported in other countries. Therefore, we concluded that for the treatment of FAP, LDLT from a living donor is equally effective as OLT from a cadaveric donor.

Adult↗
PubMed2005

[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.

Arteriosclerosis↗
PubMed2005

[Immunological and serological laboratory tests: transthyretin].

Transthyretin (TTR) is a beta-sheet rich protein whose plasma half life is 1.9 days. It behaves as a tetramer and binds to retinol binding protein (RBP) and thyroxin in plasma. Since TTR is a tryptophan-rich-protein, the protein is used as a useful marker protein for nutrition supporting team (NST). However, TTR is also an anti-acute phase protein, and the concentration is influenced by various conditions, such as inflammation and infection, Mutated forms of TTR are the precursor protein of familial amyloidotic polyneuropathy (FAP). Since plasma TTR is predominantly synthesized by the liver, liver transplantation has been performed as an effective therapy for FAP. Recent research revealed that TTR plays important roles in various central nervous system disorders, such as Alzheimer disease, depression, and lead intoxication. To elucidate the pathogenesis of those disorders, an accurate measurement of TTR concentrations in plasma and cerebrospinal fluids is of vital importance.

Amyloid Neuropathies, Familial↗
PubMed2005

Transthyretin-related familial amyloid polyneuropathy: evaluation of CSF enhancement on serial T1-weighted and fluid-attenuated inversion recovery images following intravenous contrast administration.

BACKGROUND AND PURPOSE: CSF enhancement on MR images after intravenous administration of gadolinium chelate, which mimics subarachnoid hemorrhage, has been reported. The purpose of this study was to determine whether CSF enhancement can be seen on serial MR images following administration of contrast material in patients with transthyretin-related familial amyloid polyneuropathy (FAP) and to assess other ancillary MR findings. METHODS: We serially studied T1-weighted and fluid-attenuated inversion recovery (FLAIR) images of the brain before, immediately after, and 3, 6, and 24 hours after contrast administration in 6 patients with genetically confirmed transthyretin-related FAP. By consensus, 2 radiologists assessed the presence, degree, and extent of enhancement of the CSF, leptomeninges, brain parenchyma, and other structures. Statistical analysis was performed to define the difference of the enhancement between the 2 MR imagings. RESULTS: In 3/6 patients with cysteine-for-tyrosine substitutions at position 114 (Tyr114Cys mutations), marked CSF enhancement was observed on the FLAIR images at 3 and 6 hours and on T1-weighted images at 3 hours after contrast administration. Although there was no significant difference between the 2 MR imagings, leptomeningeal enhancement for these 3 patients was evident only on FLAIR images. The labyrinth and vitreous body was also enhanced on postcontrast delayed MR images of these 3 patients. These enhancements were not observed in the other 3 patients with Val30Met mutation. In none of the 6 patients did images demonstrate parenchymal enhancement of the brain. CONCLUSION: In FAP patients with Tyr114Cys mutations, contrast material can leak into the CSF. This finding may depend on the subtype of FAP and be more evident with FLAIR images. The enhancement of the leptomeninges, labyrinth, and vitreous body was also seen in the patients.

Adult↗
PubMed2005

[Practical application of nutritional assessment protein and inflammatory marker in the nutrition support team (NST)].

Recently nutrition support team (NST) has been established for the purpose of prevention of complications which are caused by nutrition disorders and reduction of the medical expenses. Although physical examinations and blood biochemical data had been used as the indexes evaluating nutritional of patients, they were not suitable for the evaluation for the short-term in-patient. On the contrary, serum albumin (ALB) has been wildly used as a nutritional marker. However, it is impossible to evaluate nutrition state for the short-term in-patient and acute phase disease patient accurately, because the plasma half-life is 21 days and it takes long time to detect the change in nutritional state by its value. Rapid turnover proteins (RTP), whose plasma half-life is shorter, has paid attention to evaluate nutritional state for the short-term in-patients and acute phase disease patients. Although, prognostic inflammatory and nutritional index (PINI) was considered as a useful maker for evaluating inflammatory and nutritional states using the concentrations of transthyretin (TTR), a RTP, alpha1-acid glycoprotein (alpha1-AG), a chronic inflammation marker, C reactive protein (CRP), a acute inflammation marker, and ALB, However, it has several pitfalls. We newly made serum amyloid A (SAA) index using SAA instead of CRP. When we compared SAA index with PINI in many diseases, it turned out that SAA index became a more effective index which reflected the patient condition than did PINI. As for this index, it is expected to be used by NST while further alternation may be needed.

C-Reactive Protein↗
PubMed2004

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.

Adult↗
PubMed2004

A case of vitreous amyloidosis without systemic symptoms in familial amyloidotic polyneuropathy.

We describe a case of vitreous amyloidosis without systemic symptoms in familial amyloidotic polyneuropathy (FAP) associated with Val30Met transthyretin mutation. A healthy 74-year-old woman noticed left blurred vision and floaters in 1992. Severe vitreous opacities were identified in the left eye. The patient displayed no systemic symptoms, and Congo red staining of the biopsy samples of the stomach and duodenum revealed no amyloid deposition. A diagnosis of FAP was confirmed following genetic investigation. Vitrectomy and cataract surgery was performed with intraocular lens implantation in April 1998. Histopathological examination of the vitreous material revealed amyloid fibrils. Intraocular pressure (IOP) gradually elevated and cupping of the optic disc enlarged. Trabeculectomy was performed in February 2000, but postoperative IOP was again elevated and a needling procedure was performed in March 2000. No postoperative recurrence of vitreous opacity has been reported and IOP has remained well controlled. In the present case, ocular manifestations were the only symptoms of FAP and systemic symptoms have not developed, after more than 12 years. FAP should be suspected as the cause in cases of vitreous opacities in patients from areas with endemic foci of FAP.

Aged↗
PubMed2004

Amyloid imaging probes are useful for detection of prion plaques and treatment of transmissible spongiform encephalopathies.

Diagnostic imaging probes have been developed to monitor cerebral amyloid lesions in patients with neurodegenerative disorders. A thioflavin derivative, 2-[4'-(methylamino)phenyl] benzothiazole (BTA-1) and a Congo red derivative, (trans, trans),-1-bromo-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (BSB) are representative chemicals of these probes. In this report, the two chemicals were studied in transmissible spongiform encephalopathies (TSE). Both BTA-1 and BSB selectively bound to compact plaques of prion protein (PrP), not only in the brain specimens of certain types of human TSE, but also in the brains of TSE-infected mice when the probes were injected intravenously. The chemicals bound to plaques in the brains were stable and could be detected for more than 42 h post-injection. In addition, the chemicals inhibited abnormal PrP formation in a cellular model of TSE with IC(50) values of 4 nM for BTA-1 and 1.4 micro M for BSB. In an experimental mouse model, the intravenous injection of 1 mg BSB prolonged the incubation period by 14 %. This efficacy was only observed against the RML strain and not the other strains examined. These observations suggest that these chemicals bind directly to PrP aggregates and inhibit new formation of abnormal PrP in a strain-dependent manner. Both BTA-1 and BSB can be expected to be lead chemicals not only for imaging probes but also for therapeutic drugs for TSEs caused by certain strains.

Amyloid↗