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Biomedical subjects

H Yanagi

Publications and source records attributed to H Yanagi.

At least 19 recordsLinked to original sources
PubMed2002

Association of beta-fibrinogen and factor VII polymorphism with plasma fibrinogen and factor VII levels, and no association of PAI-1 polymorphism with plasma PAI-1 levels in hemodialysis patients.

AIMS: Recent studies have stressed the roles of genetic factors on the plasma levels of hemostatic markers and on cardiovascular complications. We investigated the association of DNA polymorphisms for beta-fibrinogen, factor VII, and PAI-1 with plasma levels of these factors and with ischemic heart disease (IHD) and cerebral infarction (CI) in patients undergoing hemodialysis (HD). METHODS: beta-fibrinogen G/A-455, factor VII R353Q and PAI-1 4G/5G polymorphisms were determined by PCR-RFLP in 149 HD patients and in 100 controls. The plasma levels of fibrinogen, factor VII and PAI-1 were also measured. RESULTS: The allele frequencies and the genotype frequencies of these 3 polymorphisms were not different between HD patients and controls. In HD patients, plasma fibrinogen levels were significantly lower in the GG genotype than in the GA genotype, and plasma factor VII activity was significantly higher in the RR genotype than in the RQ genotype. Multiple regression analysis disclosed that CRP and beta-fibrinogen polymorphism were the significant determinants of fibrinogen levels. Plasma PAI-1 levels were not different among the 3 genotypes. The frequency of the A-455 allele was significantly higher in HD patients with CI than in those without CI, and the genotype distribution for beta-fibrinogen differed significantly between the 2 groups. Between the same 2 groups, however, significant differences were found neither in the frequency of the 353Q or 4G allele nor in the genotype distribution for factor VII and PAI-1. No significant differences in the frequency of the G-455, 353Q or 4G alleles, or in the genotype distribution for beta-fibrinogen, factor VII and PAI-1 were observed between patients with IHD and those without IHD. Multiple logistic regression analysis demonstrated that neither polymorphism was associated with CI or IHD. CONCLUSIONS: In HD patients, beta-fibrinogen and factor VII polymorphisms affected plasma levels of fibrinogen and factor VII, respectively. Beta-fibrinogen polymorphism was not an independent but a possible risk factor for CI in HD patients. Further study will be needed to confirm the precise role of 5-fibrinogen polymorphisms in the pathogenesis of CI in HD patients.

Adult↗
PubMed2001

Regulation of tumor angiogenesis by oxygen-regulated protein 150, an inducible endoplasmic reticulum chaperone.

Expression of angiogenic factors such as vascular endothelial growth factor (VEGF) under conditions of cell stress involves both transcriptional and translational events, as well as an important role for inducible endoplasmic reticulum (ER) chaperones. Coexpression of VEGF and 150-kDa oxygen-regulated protein (ORP), a novel ER chaperone, in human glioblastoma suggested a link between angiogenesis and ORP150. C6 glioma cells stably transfected with ORP150 antisense displayed selectively reduced ORP150 expression. Tumors raised after inoculation of immunocompromised mice with ORP150 antisense C6 glioma transfectants demonstrated an initial phase of growth comparable to wild-type C6 glioma cells which was followed by marked regression within 8 days. Decreased density of platelet/endothelial cell adhesion molecule 1-positive structures within the tumor bed was consistent with reduced angiogenesis in C6 gliomas expressing ORP150 antisense, compared with tumors derived from C6 cells overexpressing ORP150 sense or vector controls. In vitro, inhibition of ORP150 expression decreased release of VEGF into culture supernatants; in ORP150 antisense transfectants, VEGF accumulated intracellularly within the ER. These findings demonstrate a critical role for the inducible ER chaperone ORP150 in tumor-mediated angiogenesis via processing of VEGF, and, thus, highlight a new facet of angiogenic mechanisms amenable to therapeutic manipulation in tumors.

Animals↗
PubMed2001

Identification of the G13 (cAMP-response-element-binding protein-related protein) gene product related to activating transcription factor 6 as a transcriptional activator of the mammalian unfolded protein response.

Eukaryotic cells control the levels of molecular chaperones and folding enzymes in the endoplasmic reticulum (ER) by a transcriptional induction process termed the unfolded protein response (UPR). The mammalian UPR is mediated by the cis-acting ER stress response element consisting of 19 nt (CCAATN(9)CCACG), the CCACG part of which is considered to provide specificity. We recently identified the basic leucine zipper (bZIP) protein ATF6 as a mammalian UPR-specific transcription factor; ATF6 is activated by ER stress-induced proteolysis and binds directly to CCACG. Here we report that eukaryotic cells express another bZIP protein closely related to ATF6 in both structure and function. This protein encoded by the G13 (cAMP response element binding protein-related protein) gene is constitutively synthesized as a type II transmembrane glycoprotein anchored in the ER membrane and processed into a soluble form upon ER stress as occurs with ATF6. The proteolytic processing of ATF6 and the G13 gene product is accompanied by their relocation from the ER to the nucleus; their basic regions seem to function as a nuclear localization signal. Overexpression of the soluble form of the G13 product constitutively activates the UPR, whereas overexpression of a mutant lacking the activation domain exhibits a strong dominant-negative effect. Furthermore, the soluble forms of ATF6 and the G13 gene product are unable to bind to several point mutants of the cis-acting ER stress response element in vitro that hardly respond to ER stress in vivo. We thus concluded that the two related bZIP proteins are crucial transcriptional regulators of the mammalian UPR, and propose calling the ATF6 gene product ATF6alpha and the G13 gene product ATF6beta.

Activating Transcription Factor 6↗
PubMed2001

Dual antitumor effects of 5-fluorouracil on the cell cycle in colorectal carcinoma cells: a novel target mechanism concept for pharmacokinetic modulating chemotherapy.

5-Fluorouracil (5-FU) is one of the most widely used anticancer agents for advanced colorectal carcinoma, but its response rate is only 15%. The "pharmacokinetic modulating chemotherapy" (PMC) regimen that we have advocated has proved to be highly effective in treating colorectal carcinoma. PMC consists of a continuous i.v. infusion of 5-FU over 24 h for 1day a week at 600 mg/m2/day, and an oral dose of uracil-tegafur (UFT), a 5-FU derivative, at 400 mg/day for 5-7 days per week, repeated every week for more than 6 months. Assays of 5-FU in 23 patients receiving this treatment showed serum concentrations ranging from 88 to 1,323 ng/ml. We then analyzed the effects of clinically relevant concentrations of 5-FU found in colorectal cancer patients treated with the PMC regimen on the growth of three human colorectal adenocarcinoma cell lines, SW480 and COLO320DM (mutant p53) and HCT116 (wild-type p53). Exposure of these three cell lines to 5-FU resulted in growth inhibition in a dose-dependent manner. Exposure to 100 ng/ml of 5-FU in SW480 and COLO320DM caused G1 arrest after 24 h and G2 arrest after 72-144 h, and only a minority of the cell population showed apoptotic features, which indicated that most of the cells were killed through mitotic catastrophe, nonapoptotic cell death. On the contrary, exposure to 1000 ng/ml of 5-FU in SW480 and COLO320DM resulted in G1-S-phase arrest and the induction of apoptosis throughout the experimental period. Nuclear cyclin B1 expression was markedly induced with exposure to 100 ng/ml of 5-FU in SW480 and COLO320DM; and expression of 14-3-3sigma protein, a cell cycle inhibitor in the GG phase, was induced in SW480. ICT116 responded to lower concentrations of 5-FU more rapidly: G2 arrest was seen after 24-72 h of exposure to 10 ng/ml of 5-FU, and G,1rrest was seen after 12-24 h of exposure to 100 ng/ml. These results show that 5-FU acts via two different pathways, depending on dose: (a) G,1S-phase cell cycle arrest and apoptosis at 1,000 ng/ml in SW480 and COLO320DM, and 100 ng/ml in HCT116; and (b) G2-M-phase cell cycle arrest and mitotic catastrophe at 100 ng/ll in SW480 and COLO320DM, and 10 ng/ml in HCT116. These results suggest that the efficacy of our PMC regimen is based on targeting at least two different phases of the cell cycle. In our clinical trial, we showed efficacy independent of p53 status, ascertained by cell kinetic analysis in vitro, which may lead to a novel concept of schedule-oriented biochemical modulation of this drug.

Adenocarcinoma↗
PubMed2001

Overproduction of bacterial protein disulfide isomerase (DsbC) and its modulator (DsbD) markedly enhances periplasmic production of human nerve growth factor in Escherichia coli.

Production of eukaryotic proteins with multiple disulfide bonds in the Escherichia coli periplasm often encounters difficulty in obtaining soluble products with native structure. Human nerve growth factor beta (NGF) contains three disulfide bonds between nonconsecutive cysteine residues and forms insoluble aggregates when expressed in E. coli. We now report that overexpression of Dsb proteins known to catalyze formation and isomerization of disulfide bonds can substantially enhance periplasmic production of NGF. A set of pACYC184-based plasmids that permit dsb expression under the araB promoter were introduced into cells carrying a compatible plasmid that expresses NGF. The efficiency of periplasmic production of NGF fused to the OmpT signal peptide was strikingly improved by coexpression of DsbCD or DsbABCD proteins (up to 80% of total NGF produced). Coexpression of DsbAB was hardly effective, whereas that of DsbAC increased the total yield but not the periplasmic expression. These results suggest synergistic roles of DsbC and DsbD in disulfide isomerization that appear to become limiting upon NGF production. Furthermore, recombinant NGF produced with excess DsbCD (or DsbABCD) was biologically active judged by the neurite outgrowth assay using rat PC12 cells.

Animals↗
PubMed2001

Is cognitive impairment a risk factor for poor compliance among Japanese elderly in the community?

OBJECTIVE: The association between cognitive impairment and compliance with prescribed medications was investigated among functionally independent Japanese elderly in the community. SUBJECTS: The subjects of this study were 220 elderly persons aged 60 years and over, who lived in the community. All participants were taking a regimen of one or more prescribed drugs. We included elderly with mild to moderate cognitive impairment. Medication use was observed by pharmacist-conducted interviews during home visits. Compliance was estimated by the pill count method. The Mini-Mental State Examination (MMSE) was used to estimate cognitive function. RESULTS: The mean age (SD) of the subjects was 75.7 (6.9) years. Of the subjects, 58 (26.4%) were cognitively impaired (MMSE < or = 23), and 76 (34.6%) exhibited poor compliance (rate of compliance< 80%). Poor compliance was associated with the subjects who had a lower education level, had lower MMSE scores, had concern about taking drugs, who intentionally self-selected (intentional noncompliance) prescribed drugs, had a poor relationship with a physician, who did not have one dose package, and those who did not use a medical calendar. In multiple logistic regression analyses, intentional noncompliance (OR 19.65, 95%, CI 9.22-41.92; OR, odds ratio; CI, confidence interval), cognitive impairment (MMSE < or = 23; OR 2.94, 95%, CI 1.32-6.58), and a poor relationship with a physician (OR 6.24. 95%, CI 1.55-25.20) were independent predictors of poor compliance for elderly in the community. CONCLUSION: We found that cognitive impairment was one of the predictors for poor compliance among the elderly who are functionally independent in the community. Intentional noncompliance was the strongest predictor for poor compliance, which was influenced by the relationship between patient and physician. Physicians should establish good communication with their elderly patients and provide some support to compensate for cognitive impairment.

Aged↗
PubMed2001

ORP150 protects against hypoxia/ischemia-induced neuronal death.

Oxygen-regulated protein 150 kD (ORP150) is a novel endoplasmic-reticulum-associated chaperone induced by hypoxia/ischemia. Although ORP150 was sparingly upregulated in neurons from human brain undergoing ischemic stress, there was robust induction in astrocytes. Cultured neurons overexpressing ORP150 were resistant to hypoxemic stress, whereas astrocytes with inhibited ORP150 expression were more vulnerable. Mice with targeted neuronal overexpression of ORP150 had smaller strokes compared with controls. Neurons with increased ORP150 demonstrated suppressed caspase-3-like activity and enhanced brain-derived neurotrophic factor (BDNF) under hypoxia signaling. These data indicate that ORP150 is an integral participant in ischemic cytoprotective pathways.

Animals↗
PubMed2001

Cytosolic chaperonin-containing t-complex polypeptide 1 changes the content of a particular subunit species concomitant with substrate binding and folding activities during the cell cycle.

The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. We show here that the content of particular subunits of CCT within mammalian cells decreases concomitantly with the reduction of chaperone activity during cell cycle arrest at M phase. CCT recovers chaperone activity upon resumption of these subunits after release from M phase arrest or during arrest at S phase. The levels of alpha, delta and zeta-1 subunits decreased more rapidly than the other subunits during M phase arrest by colcemid treatment and recovered after release from the arrest. Gel filtration chromatography or native (nondenaturing) PAGE analysis followed by immunoblotting indicated that the alpha and delta subunit content in the 700- to 900-kDa CCT complex was appreciably lower in the M phase cells than in asynchronous cells. In vivo, the CCT complex of M-phase-arrested cells was found to bind lower amounts of tubulin than that of asynchronous cells. In vitro, the CCT complex of M phase-arrested cells was less active in binding and folding denatured actin than that of asynchronous cells. On the other hand, the CCT complex of asynchronous cells (a mixture of various phases of cell cycle) exhibited lower alpha and delta subunit content and lower chaperone activity than that of S-phase-arrested cells obtained by excess thymidine treatment. In addition, turnover (synthesis and degradation) rates of the alpha and delta subunits in vivo were more rapid than those of most other subunits. These results suggest that the content of alpha and delta subunits of CCT reduces from the complete active complex in S phase cells to incomplete inactive complex in M phase cells.

Animals↗
PubMed2001

Effect of varying light intensity on maximal power production and selected metabolic variables.

This study was designed to examine the effect of exposure to two levels of light intensity (bright; 5000 lux, dim; 50 lux) prior to supramaximal cycle exercise on performance and metabolic alterations. The exercise was performed after bright and dim light exposure for 90 minutes. Ten male long-distance runners volunteered to take part in the study. They performed 45-sec supramaximal exercise using a cycle ergometer in a 500-lux. Mean power output was measured during the exercise. Lactate and ammonia in the blood and epinephrine and norepinephrine concentrations in plasma were measured at rest immediately after bright and dim light exposures and after the exercise. Bright and dim light exposure prior to exercise did not significantly affect the power output during the exercise. Blood glucose concentration immediately after exercise and plasma epinephrine during the resting period were significantly lower after bright light exposure compared with dim light exposure (p < 0.05). No significant difference was found in blood lactate, ammonia, or plasma norepinephrine levels after exercise following bright and dim light exposures. This study demonstrated that bright light stimulation prior to supramaximal exercise decreases glucose and epinephrine levels, but is not related to physical performance.

Ammonia↗
PubMed2001

DnaK chaperone-mediated control of activity of a sigma(32) homolog (RpoH) plays a major role in the heat shock response of Agrobacterium tumefaciens.

RpoH (Escherichia coli sigma(32) and its homologs) is the central regulator of the heat shock response in gram-negative proteobacteria. Here we studied salient regulatory features of RpoH in Agrobacterium tumefaciens by examining its synthesis, stability, and activity while increasing the temperature from 25 to 37 degrees C. Heat induction of RpoH synthesis occurred at the level of transcription from an RpoH-dependent promoter, coordinately with that of DnaK, and followed by an increase in the RpoH level. Essentially normal induction of heat shock proteins was observed even with a strain that was unable to increase the RpoH level upon heat shock. Moreover, heat-induced accumulation of dnaK mRNA occurred without protein synthesis, showing that preexisting RpoH was sufficient for induction of the heat shock response. These results suggested that controlling the activity, rather than the amount, of RpoH plays a major role in regulation of the heat shock response. In addition, increasing or decreasing the DnaK-DnaJ chaperones specifically reduced or enhanced the RpoH activity, respectively. On the other hand, the RpoH protein was normally stable and remained stable during the induction phase but was destabilized transiently during the adaptation phase. We propose that the DnaK-mediated control of RpoH activity plays a primary role in the induction of heat shock response in A. tumefaciens, in contrast to what has been found in E. coli.

Agrobacterium tumefaciens↗
PubMed2001

Endoplasmic reticulum stress-induced formation of transcription factor complex ERSF including NF-Y (CBF) and activating transcription factors 6alpha and 6beta that activates the mammalian unfolded protein response.

The levels of molecular chaperones and folding enzymes in the endoplasmic reticulum (ER) are controlled by a transcriptional induction process termed the unfolded protein response (UPR). The mammalian UPR is mediated by the cis-acting ER stress response element (ERSE), the consensus sequence of which is CCAAT-N(9)-CCACG. We recently proposed that ER stress response factor (ERSF) binding to ERSE is a heterologous protein complex consisting of the constitutive component NF-Y (CBF) binding to CCAAT and an inducible component binding to CCACG and identified the basic leucine zipper-type transcription factors ATF6alpha and ATF6beta as inducible components of ERSF. ATF6alpha and ATF6beta produced by ER stress-induced proteolysis bind to CCACG only when CCAAT is bound to NF-Y, a heterotrimer consisting of NF-YA, NF-YB, and NF-YC. Interestingly, the NF-Y and ATF6 binding sites must be separated by a spacer of 9 bp. We describe here the basis for this strict requirement by demonstrating that both ATF6alpha and ATF6beta physically interact with NF-Y trimer via direct binding to the NF-YC subunit. ATF6alpha and ATF6beta bind to the ERSE as a homo- or heterodimer. Furthermore, we showed that ERSF including NF-Y and ATF6alpha and/or beta and capable of binding to ERSE is indeed formed when the cellular UPR is activated. We concluded that ATF6 homo- or heterodimers recognize and bind directly to both the DNA and adjacent protein NF-Y and that this complex formation process is essential for transcriptional induction of ER chaperones.

Activating Transcription Factor 6↗
PubMed2001

Expression of the endoplasmic reticulum molecular chaperone (ORP150) rescues hippocampal neurons from glutamate toxicity.

A series of events initiated by glutamate-receptor interaction perturbs cellular homeostasis resulting in elevation of intracellular free calcium and cell death. Cells subject to such environmental change express stress proteins, which contribute importantly to maintenance of metabolic homeostasis and viability. We show that an inducible chaperone present in endoplasmic reticulum (ER), the 150-kDa oxygen-regulated protein (ORP150), is expressed both in the human brain after seizure attack and in mouse hippocampus after kainate administration. Using mice heterozygous for ORP150 deficiency, exposure to excitatory stimuli caused hippocampal neurons to display exaggerated elevation of cytosolic calcium accompanied by activation of mu-calpain and cathepsin B, as well as increased vulnerability to glutamate-induced cell death in vitro and decreased survival to kainate in vivo. In contrast, targeted neuronal overexpression of ORP150 suppressed each of these events and enhanced neuronal and animal survival in parallel with diminished seizure intensity. Studies using cultured hippocampal neurons showed that ORP150 regulates cytosolic free calcium and activation of proteolytic pathways causing cell death in neurons subject to excitatory stress. Our data underscore a possible role for ER stress in glutamate toxicity and pinpoint a key ER chaperone, ORP150, which contributes to the stress response critical for neuronal survival.

Animals↗
PubMed2001

Increased expression of cytosolic chaperonin CCT in human hepatocellular and colonic carcinoma.

The chaperonin-containing t-complex polypeptide 1 (CCT) is a hetero-oligomeric molecular chaperone that assists in the folding of actin, tubulin, and other cytosolic proteins. We recently reported that the expression level of CCT is closely correlated with growth rates of mammalian cultured cells. Here we examine the levels of CCT subunits and other molecular chaperones in tumor tissues of patients with hepatocelluar and colonic carcinoma, and compare them with nontumor tissues in the same patients. Expression levels of CCTbeta in tumor tissues was significantly higher than in nontumor tissues in all patients with hepatocellular carcinoma (n = 15) and 83% of patients with colonic carcinoma (n = 17). The increased level of CCT expression in colonic cancer cells was confirmed by immunohistochemistry with anti-CCTbeta antibody. The levels of CCTbeta were highly correlated (r = 0.606) with those of the proliferating cell nuclear antigen (PCNA), which was used as an indicator of cell growth. CCTalpha gave similar results, although the correlation with PCNA levels was weaker. Other cytosolic and endoplasmic reticulum chaperones also showed higher expression in significant numbers of tumor tissues but less frequently than that observed with CCT. These results suggest that CCT is up-regulated in rapidly proliferating tumor cells in vivo to effectively produce proteins required for growth, and may serve as a useful tumor marker because it is widely distributed in the cytosol.

Carcinoma↗
PubMed2001

[Compliance and knowledge about prescribed medication among elderly home-care recipients by method of providing medications].

After long-term care insurance commenced in April 2000, various types of in-home care began, including delivery of prescriptions medicines to the elderly. However, the effects of in-home care workers on patient drug compliance are unclear as yet. In this study, we examined the characteristics of the care workers who delivered prescription medicines to the elderly, and analyzed the effects on patient drug compliance and knowledge about medication. The subjects included 163 homecare recipients aged 60 and older, who were taking more than one prescribed drug, who ranked worse than J-2 who were physically disabled, and cognitively normal. The rate of good compliance was 71.1% when pharmacists provided the prescribed drugs and counseled the patients at home, which rate was significantly higher than that of self-supply by the patient (35.0%), caregiver supply (44.7%), and home-helper supply (0.0%). The difference in compliance may be explained by the possibility that when caregivers and home-helpers provided prescribed medications, thorough and accurate information about the drugs were not clearly imparted to the elderly, whereas when pharmacists provided prescribed medications, a pharmacological examination was performed and thorough and accurate information was communicated to the elderly. In the group counseled by pharmacists, knowledge about the effects and purpose of medication positively correlated with drug compliance. However, in the group provided drugs by caregivers, knowledge about the effects and purpose of medication inversely correlated with drug compliance. These findings suggested that the elderly in the latter group chose, to some degree, not to comply. Many elderly people had difficulty getting to hospital, and 23.1% of the patients in this study had not consulted the doctor for more than 2 months. Our data suggest that drugs provided by pharmacists and the availability of pharmacist counseling play an important role in preventing drug noncompliance and in making home care more effective, and also suggest that it is important for pharmacists to cooperate with other care workers, including a care-manager, and to provide written information on prescription medicine to caregivers and home-helpers as well as to elderly patients.

Aged↗
PubMed2001

No association found between the Ala54Thr polymorphism of FABP2 gene and obesity and obesity with dyslipidemia in Japanese schoolchildren.

To investigate whether the Ala54Thr polymorphism of the fatty acid binding protein 2 gene is associated with obesity and obesity with dyslipidemia in Japanese schoolchildren, we analyzed 370 children with morbid obesity and 463 control children of normal weight. The allele frequencies did not differ significantly between the control group and the morbidly obese group. The odds ratio (95% confidence interval CI) in obesity of the The54 allele was 1.0 (0.9-1.3). There were no significant differences in obesity index and metabolic characteristics between the two groups. The odds ratio (95% CI) in dyslipidemia of the Thr54 allele was 1.1 (0.8-1.4) in the morbidly obese group. Our data suggested that Ala54Thr polymorphism of the FABP2 gene is not a major contributing factor for obesity and obesity with dyslipidemia in Japanese children.

Adolescent↗
PubMed2001

[Long survival in a case of unresectable hepatic metastasis from rectal carcinoma treated with second-look hepatectomy plus pharmacokinetic modulating chemotherapy (PMC)].

A 67-year-old female with rectal cancer and multiple liver metastases underwent low anterior resection by total mesorectal excision (TME), cholecystectomy and hepatic arterial cannulation in June 1995. She was treated with hepatic arterial infusion chemotherapy (HAI) (5-FU 600 mg/m2/day x 2 days/w) and oral UFT (400 mg/body, 5 days/w) once a week for 6 months on an outpatient basis. As the metastatic foci of the liver significantly decreased (83.3%) and extrahepatic disease were not observed, partial resection of the liver (second-look hepatectomy) was performed in March 1996. She continued arterial infusion PMC and venous infusion PMC as an outpatient. During the follow-up period a lung metastasis appeared in November 1997. Her regimen was changed to modified PMC with MMC (mitomycin C) and CPT-11. She has been managed at our outpatient clinic while the lung metastasis remained but with no liver metastasis for 57 months after the first operation, until the present. Second-look hepatectomy and PMC with a two-way port system was a useful option for unresectable hepatic metastases from colorectal carcinoma.

Adenocarcinoma↗
PubMed2001

Corrected transposition of the great arteries diagnosed in an 84-year-old woman.

Corrected transposition of the great arteries without associated cardiac anomalies is a rare cardiac malformation. Few patients with this anomaly survive beyond 50 years of age because of systemic ventricular dysfunction or development of AV valvular regurgitation or conduction disturbance. We describe an autopsied, uncomplicated corrected transposition of the great arteries case in which the patient died at 84 years of age. We believe this patient to be the longest surviving corrected transposition of the great arteries associated person in the world.

Aged↗