Soichiro Kitamura

Tracheal replacement with cryopreserved tracheal allograft: experiment in dogs

BACKGROUNDnIt has been difficult to perform tracheal allotransplantation without immunosuppression. To determine whether cryopreserved trachea can be used in tracheal replacement, we evaluated the viability of cryopreserved tracheal allografts in a canine model of immunosuppressant-free transplantation.nnnMETHODSnCryopreserved tracheal allografts, which had been frozen to -80 degrees C in a programmed freezer and then stored in liquid nitrogen (-196 degrees C) (group 1, n = 6), fresh tracheal autografts (group 2, n = 5), and fresh tracheal allografts (group 3, n = 4) were transplanted into the thoracic segment of the trachea using an omental flap without immunosuppressive agents.nnnRESULTSnAll dogs in groups 1 and 2 survived, but in group 3, all 4 died of airway obstruction between 1 month and 2 months after operation. Histologically, the cryopreserved allografts displayed normal epithelium and cartilage, but the fresh allografts showed chronic inflammatory changes, no epithelium, and no cartilage.nnnCONCLUSIONSnCryopreserved tracheal allografts maintain their structural integrity after transplantation. The cryopreservation process seems to reduce the allogenic response of the trachea in canine models. Therefore, we believe the cryopreserved tracheal allograft is an excellent choice for tracheal replacement.

PET Quantification of Tau Pathology in Human Brain with 11C-PBB3

Tau accumulation in the brain is a pathologic hallmark of Alzheimer disease and other tauopathies. Quantitative visualization of tau pathology in humans can be a powerful method as a diagnostic aid and for monitoring potential therapeutic interventions. We established methods of PET quantification of tau pathology with 11C-PBB3 (2-((1E,3E)-4-(6-(11C-methylamino)pyridin-3-yl)buta-1,3-dienyl) benzo[d]thiazol-6-ol), considering its radiometabolite entering the brain. Methods: Seven Alzheimer disease patients and 7 healthy subjects underwent dynamic 11C-PBB3 PET scanning. Arterial blood was sampled to obtain the parent and metabolite input functions. Quantification of 11C-PBB3 binding was performed using dual-input models that take the brain metabolite activity into consideration, traditional single-input models without such considerations, and the reference tissue model (MRTMO) and standardized uptake value ratio (SUVR). The cerebellar cortex was used as the reference tissue for all methods. Results: The dual-input graphical models estimated binding parameter (BPND*) stably (∼0.36 in high-binding regions). The MRTMO BPND* matched the corresponding BPND* by the dual-input graphical model (r2 = 1.00). SUVR minus 1 correlated well with MRTMO BPND* (r2 > 0.97). However, BPND by the single-input models did not correlate with BPND* by the dual-input graphical model (r2 = 0.04). Conclusion: The dual-input graphical model BPND* is consistent with the reference tissue BPND* and SUVR-1, suggesting that these parameters can accurately quantify binding of 11C-PBB3 despite the entry of its radiometabolites into the brain.

White matter changes in dementia with Lewy bodies and Alzheimer’s disease: A tractography-based study

Dementia with Lewy bodies (DLB) and Alzheimers disease (AD) are different types of dementia. However, their clinical symptoms partially overlap and differential diagnosis is occasionally difficult. There is need for additional diagnostic criteria to reliably differentiate between these two conditions. Meanwhile, several imaging studies have showed inconsistent results between DLB and AD. The aim of this study was to use a tractography-based analysis to elucidate white matter alterations in subjects with DLB compared to those with AD and to controls. An understanding of the white matter connectivity differences between AD, DLB and controls will be helpful for differential diagnosis and an understanding of the pathophysiology. Twenty-six subjects with DLB, 26 with AD and 26 controls underwent magnetic resonance diffusion tensor imaging and neuropsychological assessment. Diffusion tensors were computed and fiber-tract maps were created using dTV II software. We measured mean fractional anisotropy (FA) values along the uncinate fasciculus (UNC), the inferior occipitofrontal fasciculus (IOFF) and the inferior longitudinal fasciculus (ILF). Both subjects with DLB and AD had lower FA values for the bilateral UNC than controls. Subjects with DLB exhibited significantly lower FA values on both sides of the IOFF and the left side of the ILF than those of controls. Although there were no significant differences between subjects with DLB and AD for any measurements, those with DLB exhibited lower FA values especially in visual-related white matter. These different changes in white matter tracts among groups could be helpful for differential diagnosis and an understanding of the pathophysiology.

Gene Transfer Into the Donor Heart During Cold Preservation for Heart Transplantation

BACKGROUNDnEx vivo gene transfer to heart grafts may hold promise as a means of changing alloreactivity or xenoreactivity after transplantation. However, it remains to be determined how effectively gene transfer can be accomplished within a short time in cold-stored grafts that are ready to be transplanted.nnnMETHODSnWe performed an experimental study using a replication-defective adenovirus (Adex1CALacZ) encoding the Escherichia coli beta-galactosidase (beta-gal) gene to perform gene transfer to heart grafts awaiting transplantation. Thirty hearts of Wistar rats were removed and their coronary arteries were perfused with University of Wisconsin solution containing 1 x 10(9), 1 x 10(10), or 1 x 10(11) plaque-forming units of the recombinant adenovirus at 4 degrees C for 60 minutes. As a control, other hearts were perfused with University of Wisconsin solution with an adenoviral vector that did not contain the beta-gal gene (Adex1w1) for the same period. After perfusion, the grafts were implanted in the necks of syngeneic adult rats. The grafts were removed each week after transplantation and their expression of beta-gal was assessed by 5-bromo-4-chloro-3-indoyl-beta-D-galactoside staining.nnnRESULTSnSuccessful gene transfer and expression of the beta-gal gene were demonstrated in adenovirus-perfused hearts. Gene transfer occurred preferentially in the cardiomyocytes over the endothelial cells and smooth muscle cells of the coronary vessels. In hearts perfused with 1 x 10(9) plaque-forming units of the adenovirus, gene expression persisted for 4 weeks after transfer, but it diminished gradually and was minimal by day 28. Histologic analyses revealed slight inflammatory reactions in the myocardium. In hearts perfused with 1 x 10(10) and 1 x 10(11) plaque-forming units of the adenovirus, beta-gal diminished 3 weeks after transplantation and a prominent infiltration of leukocytes was recognized in the myocardium.nnnCONCLUSIONSnThis study demonstrated that the cardiomyocytes of heart grafts express an exogenous gene product after adenovirus-mediated gene transfer under hypothermic preservation conditions. However, immune or inflammatory reactions to recombinant adenoviruses must be taken into account when a large number of adenoviruses are injected into the coronary arteries.

Longitudinal white matter changes in Alzheimer's disease: a tractography-based analysis study.

Alzheimers disease (AD) classically presents with gray matter atrophy, as well as feature significant white matter abnormalities. Previous evidence indicates the overall burden of these pathological changes continues to advance as the disease progresses. The aim of this study was to investigate whether pathological alterations of white matter tracts correlate with the course of AD disease progression. 35 AD patients and 29 normal controls were recruited to the study and administered baseline magnetic resonance diffusion tensor imaging (DTI) acquisition and a cognitive function assessment at the time of initial evaluation. Subjects were re-evaluated with secondary DTI scan and cognitive function assessment at intervals of about 1.5 years on average. For the DTI acquired scans, we calculated diffusion tensor parameters, fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial diffusivity (DR), and axial diffusivity (DA) along with the uncinate fasciculus (UNC), the inferior longitudinal fasciculus (ILF), and the inferior occipitofrontal fasciculus (IOFF). Compared to baseline, a significant mean FA reduction of the bilateral UNC, as well as a significant mean DR increase of the left UNC, was evident in AD patients at follow-up. Compared with normal controls, AD patients exhibited significant diffusion parameter abnormalities in their UNC, ILF, and IOFF. Taken together, these results indicate that progressive pathological white matter alterations can be quantified using the DTI parameters utilized here and may prove to be a useful biological marker for monitoring the pathophysiological course of AD.

Long-term Benefits of Internal Thoracic Artery-Coronary Artery Bypass in Japanese Patients

OBJECTIVESnThis study sought to determine the effects of grafting the internal thoracic artery (ITA) to the left anterior descending coronary artery (LAD) on long-term (10-year) survival, the cardiac death-free rate, and on the cardiac event-free rate in Japanese patients.nnnBACKGROUNDnThe use of ITA grafts has been reported to enhance postoperative survival and to decrease the occurrence of cardiac events in the Western literature. However, the survival benefits in Japanese patients, who may have different prognoses with coronary artery disease and a different fate of a saphenous vein graft, have not yet been determined.nnnSUBJECTS AND METHODSnA total of 954 consecutive patients who underwent coronary artery bypass graft operations (CABG) during the last 12 years at the Nara Medical University were followed and evaluated. Of these, 713 patients underwent ITA-CABG to at least the LAD (ITA group), and 241 patients received a saphenous vein graft (SVG) to the LAD (SVG group). At the time of operation, no significant difference was found between these two groups in age, sex ratio left ventricular ejection fraction, left ventricular end-diastolic pressure, cardiac index, incidence of unstable angina, or in the necessity for an emergency operation. However, those patients who received ITA-CABG had significantly higher incidences of diabetes mellitus, hyperlipidemia, and left main coronary artery disease.nnnRESULTSnThe 10-year cumulative graft patency rate for the LAD was 23% higher in the ITA group (90.3%) compared to the SVG group (67.0%), (p < .0001). Despite increased preoperative risk factors, patients in the ITA group showed significant improvements in their 5- and 10-year cumulative survival rates as well as in their cardiac death-free and event-free rates. Furthermore, this study demonstrated that ITA grafts improved the prognoses of patients with diabetes mellitus or left ventricular dysfunction and lowered both the long-term postoperative cardiac-death rate and the cardiac-event rate.nnnCONCLUSIONSnThe use of ITA grafts was effective in improving both the postoperative survival and cardiac event-free rates, and should be recommended in patients with diabetes mellitus or left ventricular dysfunction. ITA grafting to the LAD should be a routine operation in almost all categories of such patients.

Comparative Rest and Exercise Hemodynamics of Allograft and Prosthetic Valves in the Aortic Position

BACKGROUNDnAllograft aortic valve replacement has gained widespread acceptance. However, there is little information about in vivo allograft valve function at rest and during exercise.nnnMETHODSnCardiac catheterization was performed to measure hemodynamic variables at rest and during supine bicycle exercise in 44 patients who had had aortic valve replacement using allograft valves or Bicer or St. Jude Medical prosthetic valves 19 to 27 mm in diameter. Sixteen patients received an allograft valve; 17, a Bicer valve; and 11, a St. Jude Medical valve. There were no significant differences between the three groups in age, body surface area, left ventricular end-systolic and end-diastolic volume indices, exercise cardiac index, exercise heart rate, or work load achieved. Left ventricular and ascending aortic pressures were measured simultaneously according to the transseptal method.nnnRESULTSnThe mean pressure gradient was generally higher for the Bicer and St. Jude Medical valves than for the allograft valves, both at rest and during exercise. Significant differences were obtained in patients with small-sized valves (21 and 23 mm); pressure gradients were higher in the prosthetic valve groups. In patients with large-sized prosthetic valves (25 mm), there were no significant differences between the three groups at rest and during exercise. However, there was no pressure gradient at all for allograft valves.nnnCONCLUSIONSnExercise cardiac catheterization confirms that the allograft aortic valve is an ideal substitute from the hemodynamic aspect, particularly in patients with a small aortic root and in those who perform strenuous exercise.

Association between Aβ and tau accumulations and their influence on clinical features in aging and Alzheimer's disease spectrum brains: A [11C]PBB3-PET study

Amyloid‐β (Aβ) and tau accumulations may occur independently and concurrently as exemplified by primary age‐related tauopathy and Alzheimers disease (AD), respectively. Interactions between Aβ and tau accumulations and their influence on clinical features, however, are still unclear.

Preparation and Recellularization of Tissue Engineered Bioscaffold for Heart Valve Replacement

Tissue engineered grafts based on polymeric or acellular xenogeneric matrices have been widely studied, and found to have greater durability and functionality with growth potential and less immunogenicity than current bioprostheses. On the other hand, there are still several problems to be solved such as degradation control of biodegradable polymeric scaffolds and unwanted transfer of unknown animal related infectious diseases. In this chapter, our novel tissue processing of decellularization named PowerGraft by ultrahigh pressure treatment for safe tissue transplantation is reported. Porcine heart valves were isolated under sterile conditions and treated by cold isostatic pressing (CIP) at 4°C for disruption of donor cells. The cell debris was then washed out in PBS under microwave irradiation at 4°C. The tissues were completely cell free when they were treated by a CIP of 980 MPa (10,000 atm) for 10 min. There was no porcine endogeneous retrovirus (PERV) detected in the treated tissue. There were no significant changes in biomechanical properties of breaking strength and elastic modulus. From the in vitro incubation test, the tissues were disinfected when CIP was applied to the tissues contaminated by normal bacteria floras. The endothelial cells were well seeded on the acellular bioscaffold by the roller and circulation culture systems sequentially. This PowerGraft processing may provide a more durable and safe bioscaffold for tissue transplantation.

Delayed atrophy in posterior cingulate cortex and apathy after stroke

A few studies have been performed on chronic structural changes after stroke. The primary purpose of the present study was to investigate regional cortical volume changes after the onset of stroke and to examine how the cortical volume changes affected neuropsychiatric symptoms.