Possibility of xenotransplantation with a cryopreserved porcine heart valve in a canine model.
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Biomedical subjects
Publications and source records attributed to H Sakaguchi.
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BACKGROUND/AIMS: We recently demonstrated prion as a new marker for hepatic stellate cell activation in rats. Here, we have examined prion expression in normal and diseased human livers. METHODS: Prion expression was examined at protein level by immunohistochemistry and at mRNA level by in situ hybridization. RESULTS: While normal livers were negative for prion, all liver specimens but one from patients with chronic liver disease were positively stained. In chronic hepatitis, prion protein expression was found not only in the sinusoidal lining cells within the lobules but also in mesenchymal cells in expanded portal tracts. In alcoholic liver disease, prion-positive cells were found mainly in the areas of alcoholic hepatitis. Immunoelectronmicroscopy revealed that prion-positive cells were activated stellate cells. In situ hybridization demonstrated that the distribution of prion mRNA is similar to that of prion protein. In chronic hepatitis, the number of prion-positive cells correlated with the grade of activity but not with the stage of fibrosis. In alcoholic liver disease, levels of prion protein expression were significantly increased in the presence of alcoholic hepatitis. CONCLUSION: Prion as a novel marker of activated stellate cells correlates well with disease activity in human chronic liver diseases.
The relative overexpression of oestrogen receptor (ER)-alpha exon 5 splicing variant (ER-alpha E5SV), ER-beta and progesterone receptor (PR) from B (PR-B) without transcriptional repression by PR from A (PR-A) might be related to the metastatic potential and partially cause deviation from sex steroidal dependency in endometrial cancers.
Dysregulation of apoptosis, particularly in the Fas/Fas ligand (FasL) pathway, is considered to be involved in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Recently, a soluble decoy receptor, termed decoy receptor 3 (DcR3), that binds FasL and inhibits FasL-induced apoptosis, has been identified. Silicosis is clinically characterized not only by respiratory disorders but by immunological abnormalities. We have found that serum soluble Fas (sFas) levels are elevated in silicosis patients and that sFas message is dominantly expressed in PBMC derived from these patients. This study examined DcR3 gene expression in PBMC derived from patients with silicosis, SLE, or progressive systemic sclerosis (PSS), and compared it with that in healthy volunteers (HV). The relative expression level of the DcR3 gene was examined in PBMC derived from 37 patients with silicosis without clinical symptoms of autoimmune disease, nine patients with SLE, 12 patients with PSS, and 28 HV using the semiquantitative multiplex-reverse transcriptase-polymerase chain reaction (MP-RT-PCR). The correlation between the relative expression level of the DcR3 gene and multiple clinical parameters for respiratory disorders and immunological abnormalities in individuals with silicosis was analysed. The DcR3 gene was significantly over-expressed in cases of silicosis or SLE when compared with HV. In addition, the DcR3 relative expression level was positively correlated with the serum sFas level in silicosis patients. It is unclear, however, whether over-expression of the DcR3 gene in silicosis is caused by chronic silica exposure, merely accompanies the alteration in Fas-related molecules, or precedes the clinical onset of autoimmune abnormalities. It will be necessary to study these patients further, establish an in vitro model of human T cells exposed recurrently to silica compounds, and resolve whether the increase in DcR3 mRNA expression is a cause or consequence of disease.
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BACKGROUND AND STUDY AIMS: Several different effective forms of treatment are available, singly or in combination, for patients with hepatocellular carcinoma (HCC). These include surgical resection, transcatheter arterial embolization, percutaneous ethanol injection, and percutaneous microwave coagulation therapy. In this study, we carried out laparoscopic microwave coagulation therapy (LMCT), using laparoscopic microwave electrodes to treat HCC. PATIENTS AND METHODS: Under local anesthesia, 24 patients with HCCs located on or near the liver surface underwent LMCT under direct laparoscopic vision, with ultrasound guidance. LMCT was performed using microwave electrodes with tips ranging from 15-45 mm in length, and the effectiveness of the treatment was confirmed using contrast-enhanced computed tomography (CT) within two weeks of the LMCT procedure. RESULTS: The mean longest axis of the 26 HCC nodules in 24 patients was 20 mm, and that of the coagulated areas including the nodules was 40 mm, with additional therapy being required in two patients. Complete efficacy of the treatment was observed in 21 patients (87.5%), but local recurrences were seen in three of them one year after LMCT. The three-year survival rate was 92%, but the number of patients included in the study was small. Hemostasis was complete, but mild pneumothorax occurred in three patients. CONCLUSIONS: LMCT under local anesthesia is a minimally invasive and effective therapy when carried out on a single occasion to treat HCCs located near the liver surface, and it can be safely performed under direct visual guidance.
We study a population of identical Rössler oscillators with global coupling. When the coupling constant is increased, an order-disorder-type phase transition occurs. Partial phase synchronization occurs in the ordered phase, although the amplitude of the oscillation is randomly distributed. We analyze the phase transition with a self-consistent method.
We study Gledzer-Ohkitani-Yamada shell models with heat reservoirs. Time-reversible Nose-Hoover dynamics are used for the heat reservoirs. Both equilibrium and nonequilibrium cascade states are obtained by changing the heat reservoirs.
The Kuramoto-Sivashinsky equation with fixed boundary conditions is numerically studied. Shocklike structures appear in the time-averaged patterns for some parameter range of the boundary values. Effective diffusion constant is estimated from the relation of the width and the height of the shock structures.
Novel human estrogen receptor (ER)-beta was identified in cDNA libraries from human testis. ER-beta specifically expresses in testis, ovary, thymus, spleen, osteoblasts and fetus. ER-beta might not conserve the same physiological functions as does ER-alpha. Therefore, the clinical significance of the expression of ER-alpha and ER-beta mRNAs in ovarian cancers was investigated. The percentage of ER-beta mRNA to ER-alpha mRNA ranged from 1.5 to 10% in normal ovaries. On the other hand, the ratios of ER-beta mRNA to ER-alpha mRNA were in a wide range in ovarian cancers. There was no significant difference in the ratios among ovarian cancers classified according to histological types or clinical stages. In a 48-month survival rate, the patient prognosis in ovarian cancers with a low or high ratio of ER-beta mRNA to ER-alpha mRNA (<1.5 or >10% of ER-beta mRNA to ER-alpha mRNA) was significantly worse than that in ovarian cancers with a medium ratio (>==1.5 to <==10% of ER-beta mRNA to ER-alpha mRNA). In conclusion, the intact synchronized expression of ER-beta mRNA interacting with ER-alpha mRNA might be damaged in some ovarian cancers, which might lead to poor patient prognosis.
PURPOSE: To evaluate the feasibility and efficacy of a newly designed stent-graft placed across the renal arteries for exclusion of abdominal aortic aneurysms (AAAs) with short or tortuous proximal necks. METHODS: Among a group of AAA patients treated with endovascular grafting, 5 had tortuous proximal necks and 13 had necks <20 mm (mean 13 mm). In these 18 cases, a 2- to 3-cm uncovered segment of the stent-graft was placed transrenally using a catheter inserted into the renal artery as a guide for graft margin positioning. A newly designed stent-graft was constructed from a custom-made spiral Z-stent covered with a thin-walled Dacron material; the endografts were deployed through 16-F (aortoaortic model) or 18-F sheaths (bifurcated devices). Renal function was assessed by preoperative and postoperative measurement of urea nitrogen and creatinine. Aneurysm exclusion and renal artery patency were evaluated during follow-up using spiral computed tomography and angiography. RESULTS: The stent-grafts were correctly placed at the intended site in all 18 patients. Renal function was not affected except transiently in 1 patient who developed bilateral renal artery stenoses 24 hours after the procedure; Palmaz stents were deployed in each renal artery to reestablish satisfactory blood flow. Of the 33 renal arteries crossed by the bare stent-graft segment, all were patent over a mean 14-month follow-up (range 7-24), including the patient with Palmaz stents implanted for postprocedural renal stenosis. Complete aneurysm exclusion was maintained in 15 (83%) of 18 patients; proximal leaks persisted in 3 patients, including 2 with severely angled proximal necks. CONCLUSIONS: Transrenal placement of the uncovered leading edge of custom-made spiral Z-stent-based endografts appears feasible and clinically effective in the treatment of AAAs with short or tortuous proximal necks.
Surgical reduction of pulmonary allografts is being performed because of the shortage of allografts of suitable size for pediatric use. However, the outcome of size-reduced pulmonary allografts for pulmonary conduits is unknown. In the present study, cryopreserved pulmonary allografts harvested from adults at the time of kidney donation were size-reduced and used in 4 children, 2 with pulmonary atresia and ventricular septal defect and 2 with atrioventricular discordance, pulmonary atresia and ventricular septal defect. They all had undergone right and/or left modified Blalock-Taussig shunt operations with a 5-mm synthetic graft prior to the reparative operations. They underwent definitive repair with a size-reduced cryopreserved pulmonary allograft valved conduit and were followed up for 2-5 years. Postoperative echocardiographic and cineangiographic assessments revealed excellent function of the pulmonary bicuspidalized valves with a minimal pressure gradient and no, or only trivial, regurgitation. Although the long-term result of a cryopreserved bicuspid pulmonary valved conduit remains unknown, the remodeled bicuspid pulmonary allograft conduits showed excellent hemodynamic characteristics in mid-term follow-up and appear to be a reasonable alternative to other types of conduits when an appropriate-sized allograft is not available.
Systemic venous return to the heart is disturbed as a result of right heart failure. ICG clearance is known to be influenced by hepatic venous return to the right atrium. Under a hypothesis that right heart function could be evaluated by ICG clearance test, patients with mitral valve disease (Group M, n = 29), aortic valve disease (Group A, n = 16), ischemic heart disease (Group CABG, n = 19) were studied. Preoperative K-ICG (normal range > 0.17) in the Group M was significantly lower than those in the Group A and Group CABG (0.097 +/- 0.037 vs 0.166 +/- 0.032 and 0.171 +/- 0.027, p < 0.05). In the Group M, patients who underwent tricuspid annuloplasty (TAP) had significantly lower K-ICG than the others (0.077 +/- 0.026 vs 0.113 +/- 0.038, p < 0.05). Postoperatively, K-ICG of TAP patients significantly increased (0.092 +/- 0.031, p < 0.05) when compared to their preoperative value. ICG clearance test was useful to quantify the right heart function, especially in the postoperative evaluation.
The number of dysplastic nodules detected clinically has increased since patients with hepatitis virus-associated cirrhosis, who are at increased risk for hepatocellular carcinoma (HCC), began to undergo regular cancer surveillance. Although it is potentially important to determine which type(s) of nodule may be prone to progress to HCC, outcomes of dysplastic nodules have not been fully investigated. This prompted us to examine the outcomes of dysplastic nodules in cirrhotic patients clinicopathologically. We studied 33 dysplastic nodules of <20 mm in maximum diameter, diagnosed by fine needle aspiration biopsy under ultrasonography (US). These nodules were clinically followed, mainly by US examination, for up to 70 months. When the nodules enlarged or exhibited changes on US, they were histologically reexamined by second biopsy. Surprisingly, 15 of the 33 nodules (45.5%) disappeared, 14 nodules (42.4%) remained unchanged, and only 4 nodules (12.1%) progressed to HCC. The latter 4 nodules were all hyperechoic on US and were composed of clear cells with fatty change or small cells with increased nuclear density, and in all 4 patients serum was positive for hepatitis C virus antibody. Univariate analyses revealed that, although not significant, the hyperechoic nodules or nodules with small cell change showed a higher HCC progression rate in comparison with the hypoechoic nodules or the nodules without small cell change. In summary, most of the dysplastic nodules we followed disappeared or remained unchanged, but some progressed to HCC. Hyperechoic nodules in patients with hepatitis C virus-associated cirrhosis, which show small cell change with increased nuclear density, may be prone to progress to HCC.
A 24-year-old woman presented with an abnormal sound in her neck. She had no history of previous surgery, endotracheal intubation or neck trauma. She had been aware of this abnormal sound since she was 12 years old, but paid no attention to it. She had been recommended to visit a hospital for a neck examination. Stridor was heared in the neck ["coming from the throat"?]. Peak flow was markedly suppressed in pulmonary function tests, and the flow volume loop indicated upper airway stenosis. Bronchoscopy revealed subglottic tracheal stenosis, and magnetic resonance imaging showed that the cricoid cartilage was normal. Nd-YAG laser treatment was performed in Mitsui Memorial Hospital and her symptoms were improved. Biopsy of the stenotic area of the trachea showed dense fibrous tissue proliferation in the submucosa. Neither granuloma nor vasculitis was found in the biopsy specimen. No systemic disease capable of inducing tracheal stenosis was found on systemic examination. From these clinical and pathological findings, we diagnosed idiopathic subglottic stenosis.
A 25-year-old woman suffered a massive deep vein thrombus in her left common iliac vein extending to the inferior vena cava after an abdominal cesarean section. The massive and floating inferior vena cava thrombus was considered to pose a high risk of pulmonary thromboembolism. After placement of a temporary inferior vena cava filter via the left brachial vein, thrombolytic therapy and anticoagulation therapy were instituted. The filter successfully prevented pulmonary thromboembolism during thrombolytic therapy. This patient was confined to bed because the filter moved vertically with left shoulder joint abduction. Although a temporary inferior vena cava filter is very useful for the prevention of pulmonary thromboembolism in a patient with deep vein thrombus, the appropriate range of activity for such a patient needs careful consideration.
Recent investigations of the cytokine network surrounding myeloma cells have disclosed the importance of gp130-related cytokines including interleukin (IL)-6 for myeloma cell survival and proliferation, identification of IL-10 as a growth factor for myeloma cells, the close relationship between IL-10 and the receptors for gp130-related cytokines, and the growth enhancement effect of IL-11 and IL-7 on myeloma cells. In this study, IL-10 production was observed in three out of seven human myeloma cell lines examined and five (including three producing lines) out of 10 lines exhibited mRNA expression of IL-10. The IL-10 mRNA expression was also enhanced in approximately one third of primary specimens, whereas the IL-10 receptor (R) expression was not changed compared with that of normal component marrow controls. However, reverse transcription-polymerase chain reaction (RT-PCR) assay of various cytokines and their receptors showed no particular association with IL-10-producing myeloma lines compared with non-producing lines. Supplementing exogenous IL-10 or neutralization of the IL-10 signal by anti-IL-10 monoclonal antibody (mAb) in a culture conditions did not significantly affect myeloma cell growth regardless of expression of IL-10 or its receptor (IL-10R). However, supplement of anti-IL-10 mAb caused upregulation of certain genes such as IL-11, leukaemia inhibitory factor receptor (LIFR) and syndecan-1 in IL-10R-expressing cell lines. These findings indicate that the cytokine network surrounding myeloma cells is complicated and variable. In addition, IL-10 may modify this network and the cellular biological properties of myeloma cells rather than cell proliferation.
A 73-year-old woman presented to our hospital with epigastric pain and swelling of the left upper limb. Enlarged lymph nodes with adhesion were palpable in the left cervical region and supraclavicular fossa. Tests were performed with the thought that the left upper limb swelling was secondary to venous compression by the enlarged lymph nodes. Gastroscopy detected a torose lesion on the anterior wall at the gastric angle and biopsy revealed that it was moderately differentiated adenocarcinoma. MRI showed metastasis to the sixth cervical vertebra and the first thoracic vertebra. Based on these findings, she was diagnosed as having progressive gastric cancer with metastasis to Virchow's lymph node and the cervical and thoracic vertebrae. Because it was considered impossible to perform radical gastrectomy, chemotherapy was given. Since renal dysfunction was suggested by a serum Cr of 1.5 mg/ml and a Ccr of 26.2 ml/min, TS-1 was administered at a lower dose (50 mg/day for 4 weeks) than usual, followed by 2 weeks off therapy to complete 1 course. During TS-1 therapy, the plasma 5-FU concentration at 4 h was 129.5 ng/ml, indicating that an effective plasma level of the drug was achieved. TS-1 therapy was considered effective because it reduced the diameter of the primary tumor and the lymph node metastasis, with only mild adverse reactions including myelosuppression.