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Biomedical subjects

M Imamura

Publications and source records attributed to M Imamura.

At least 109 records · Page 6Linked to original sources
PubMed2001

Regulation of cell proliferation using tissue engineering in MIN6 cells.

Pancreatic islet transplantation for patients with diabetes mellitus has been hindered by the problem of donor shortage, as is the case for transplantation of other organs. Among several measures to overcome this problem, cell transplantation using xenogenic cell lines has been considered. For the treatment of diabetic patients, a murine pancreatic beta-cell line MIN6 is a potential source of cell transplant. In order to restrict otherwise unlimited proliferation of transplanted MIN6 cells, cells are rendered to form spheroidal aggregates (SMIN6) on nonadherent culture dishes. SMIN6 stopped its growth around day 7 with a diameter of 220 +/- 40 microm and kept its size almost constant at least until day 28. SMIN6 cells, however, had reduced responsiveness of insulin secretion to glucose concentration compared with MIN6 cells cultured in a monolayer. On the other hand, spheroid MIN6 cells formed in the presence of extracellular matrix gel (SMIN6E) possessed the capacity for glucose-dependent insulin secretion comparable with conventional MIN6 cells. SMIN6E encapsulated in agarose beads (SMIN6E-B) was also viable for at least 1 month in vitro with a constant diameter and favorable glucose responsiveness. The development of spheroid-type MIN6 may contribute to the future clinical application of MIN6 or other beta-cell lines for treatment of diabetes mellitus.

Animals↗
PubMed2001

Tissue-engineered pancreatic islets: culturing rat islets in the chitosan sponge.

Subcutaneous islet transplantation has become an attractive modality. With development of tissue-engineering techniques, it is possible to rectify the disadvantage of poor blood supply in the subcutaneous site by reconstruction of the capillary network. According to reports, the Chitosan sponge (CS) could be used for reconstruction of in vitro capillary-like network and could be used in artificial skin equivalent. In this study, we cultured the islets in CS for future application. CSs, having 200-500 microm pore size, were prepared by freeze-drying method. Rat islets were isolated from the pancreas of Lewis rats (10 weeks old, 280-300 g, male) by collagenase digestion followed by discontinuous dextran gradient centrifugation method. Each 20 islets were seeded equally into the CSs and were cultured for 62 days with various culture media such as RPMI-1640, Dulbecco's modified Eagle's medium (DMEM), and Eagle's MEM. They contained 10% fetal bovine serum (FBS) and 5 ml/L antibiotic-antimycotic mixed stock solution in the culture dishes. Insulin concentration both inside and outside of the islet-seeded CS was measured during culture. Changes in the morphology of islets were also observed in this study. Freshly isolated islets had a loose appearance with an irregular border, and most were seen as a single islet. Occasionally a cluster, consisting of 2-4 islets ranging mainly from 150 to 250 microm in diameter, was observed. Islets cultured in the CSs in different culture media retained initial morphology, which had well-delineated smooth borders for at least 53 days. The insulin release behavior of islets cultured in the CS showed constant secretory capacities for 49 days. After that they exhibited a rapid and definitive decline from the initial insulin release. Until this stage, insulin concentration in the CS was well maintained. The properties were dependent on culture medium used and insulin diffusion released from islets. This experiment is a new study model for establishment of islet culture in a three-dimensional matrix. Also extension of this observation will provide new insights for islet transplantation at the subcutaneous site by a tissue-engineering approach.

Animals↗
PubMed2001

[Grafting and concomitant left ventricular myotomy-myectomy in a patient with coronary artery disease associated with hypertrophic obstructive cardiomyopathy].

A 44-year-old man complained of chest oppression and systolic murmur. Echocardiography showed subaortic stenosis with outflow gradient of 135 mmHg, interventricular septal thickness of 21 mm, left ventricular posterior wall thickness of 11 mm, and 2/4 mitral regurgitation. Selective coronary angiography demonstrated 75% stenosis in left anterior desending branch. Coronary artery revasculization comcomitant with left ventricular myotomy-myectomy was performed. He had a good recovery from operation, and was discharged in 19th days in NYHA class I. Echocardiography one month after operation showed mild outflow pressure gradient, light systolic anterior motion of mitral anterior leaflet, and 1/4 mitral regurgitation. Careful operative management, including myocardial protection, avoiding perporation of ventricular septum, and postoperative medical care are mandatory to this group of patients. The use of cathecholamine and Ca-blocker will be attentioned because of the increasing the left ventricular pressure gradient.

Adult↗
PubMed2001

Brain natriuretic polypeptide in type 2 NIDDM patients with albuminuria.

We investigated plasma brain natriuretic polypeptide (BNP) in Type 2 NIDDM patients with albuminuria. This study involved normal control subjects (Controls), hypertensive patients without diabetes mellitus (HT) and Type 2 NIDDM patients. Diabetic patients were divided into 4 groups by urinary albumin index (Alb-I): group I <30; group II 30-149; group III 150-300; group IV >300 mg/g creatinine. BNP levels in group III or IV were significantly higher than in Controls. The diabetic patients were re-divided into 4 groups (DM: with neither diabetic retinopathy (which was one of indicators of microangiopathy) nor hypertension, DM+HT: without diabetic retinopathy and with hypertension, DM+R: with diabetic retinopathy and without hypertension and DM+R+HT: with both diabetic retinopathy and hypertension). The Alb-I levels in DM+HT and DM+R+HT were significantly higher than the Controls, indicating the development of diabetic nephropathy in those groups. BNP levels in DM+HT, DM+R or DM+R+HT were significantly higher than in Controls. This indicates that BNP levels elevate in diabetic patients with increased albuminuria due to hypertension or microangiopathy deteriorating diabetic nephropathy. Elevated plasm BNP may play a pathophysiological role in the development of diabetic nephropathy.

Albuminuria↗
PubMed2001

17alpha-hydroxylase deficiency accompanied by adrenal myelolipoma.

A 45-year-old woman was admitted because of hypertension and hypokalemia. Primary amenorrhea from birth was noted. Plasma renin activity (PRA), 17alpha-hydroxyprogesterone and androgen levels were low, but progesterone, 11-deoxycorticosterone, corticosterone and adrenocorticotropic hormone (ACTH) were elevated, resulting in a diagnosis of 17alpha-hydroxylase deficiency. Abdominal magnetic resonance imaging revealed a round mass in the left adrenal region, the specimen of which was diagnosed as myelolipoma. After removal of the tumor, the blood pressure, serum potassium and hormone levels were unchanged, indicating an adrenal non-functioning tumor. Excessive ACTH secretion over a long period may stimulate the development of adrenal myelolipoma.

17-alpha-Hydroxyprogesterone↗
PubMed2001

A case of intraoperative acute aortic dissection caused by cannulation into an axillary artery.

Severe atherosclerotic disease of the ascending aorta is one of the risk factors of dissection of the ascending aorta and cerebral embolism during cardiac operations with cardiopulmonary bypass. Aortic dissection is rare, but once it happens, the mortality rate is high. For the patient with severely atherosclerotic or strongly calcified aorta, we should avoid cannulation into the aorta or clamping of it. In this case, we experienced aortic dissection although we chose the arterial cannulations into the axillary arteries because of the strong calcification of the ascending aorta and the abdominal aorta. The dissection was caused by the cannulation into the axillary artery. Transesophageal echocardiography (TEE) showed the dissection during the operation and the ascending aorta was replaced soon. Early diagnosis and treatment saved the patient. This case showed the following points: 1) cannulation into an axillary artery is not always safe; 2) TEE is very useful to detect the complicated dissection during operation; 3) replacement of the ascending aorta alone can be one of the choices for the treatment of aortic dissection caused by cannulation into an axillary artery.

Aged↗
PubMed2001

Expression of METH-1 and METH-2 in pancreatic cancer.

PURPOSE: METH-1/hADAMTS-1 and METH-2/hADAMTS-8 are recently identified genes that inhibit angiogenesis, and the murine homologue, ADAMTS-1, shows metalloproteinase function. Because the significance of METH-1 and METH-2 has not been determined in solid tumors, we examined the mRNA expressions of these molecules in pancreatic cancer and hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: METH-1 and METH-2 mRNA expressions were identified in six pancreatic cancer cell lines and were quantified by TaqMan reverse transcription-PCR in 18 paired samples of pancreatic cancer and surrounding noncancerous pancreas, and in 14 samples of pancreatic cancer. METH-1 mRNA expression was also examined in 16 pairs of HCC and cirrhotic liver. Vascularity was estimated by CD34 staining. The correlation between clinicopathological factors and METH-1 expression was additionally analyzed. RESULTS: Four of six pancreatic cancer cell lines expressed METH-1, and 1/6 expressed METH-2. METH-1 was substantially expressed in both pancreatic cancer and noncancerous pancreas, but METH-2 was not. METH-1 expression in pancreatic cancer tissue was significantly lower than that in noncancerous pancreas (P = 0.002), and a similar result was obtained between HCC and cirrhotic liver (P = 0.003). METH-1 expression did not show a significant correlation with vascularity in pancreatic cancer or in HCC. However, pancreatic cancer with higher expression of METH-1 showed significantly severe lymph node metastasis or retroperitoneal invasion (P = 0.033 and P = 0.018, respectively) and worse prognosis (P = 0.038). CONCLUSIONS: METH-1, which was initially reported to have a potent antiangiogenic effect, does not seem to be a predominant determinant of tumor vascularity in pancreatic cancer. Rather, METH-1 seems to be involved in progression of pancreatic cancer through local invasion and lymph node metastasis.

ADAM Proteins↗
PubMed2001

[Mixed type of total anomalous pulmonary venous return: a rare pattern of pulmonary venous drainage].

The occurrence of multiple drainage sites in total anomalous pulmonary venous return (TAPVR) has important implication in preoperative diagnosis and surgical treatment. We report a rare pattern of pulmonary venous drainage with the right upper pulmonary vein draining into the innominate vein and the other three pulmonary veins into the portal vein (Ib + III type). The preoperative diagnosis was made by echocardiography and confirmed by angiography. In operation, an anastomosis was made between the common pulmonary vein and the left atrium through posterior approach, but the right upper pulmonary vein was left uncorrected because the anomalously draining blood flow of a single pulmonary vein was about 20% of total pulmonary blood flow. The postoperative course was uneventful, however, the long-term follow-up is mandatory because of the right upper pulmonary vein being left uncorrected.

Anastomosis, Surgical↗
PubMed2000

Delayed (18)F-fluoro-2-deoxy-D-glucose positron emission tomography scan for differentiation between malignant and benign lesions in the pancreas.

BACKGROUND: Positron emission tomography (PET) using (18)F-fluoro-2-deoxy-D-glucose (FDG) has been used for the evaluation of various tumors, but accumulation in inflammatory lesions makes it a controversial modality. The aim of this study was to investigate the usefulness of delayed scanning in differentiation between malignant and benign lesions in the pancreas. METHODS: Forty-seven patients with suspected pancreatic carcinoma were studied by FDG-PET. All patients received approximately 370 megabequerels of FDG after a transmission scan, and an emission scan was performed 1 hour and 2 hours later for all patients. A subset of 19 patients was also scanned at 3 hours postinjection. The standardized uptake value (SUV) was determined, and the retention index was calculated by dividing the increase in the SUV between 1 hour and 2 hours postinjection by the SUV at 1 hour postinjection. RESULTS: Of 27 malignant lesions, the SUVs of 22 lesions increased at 2 hours postinjection, whereas the FDG uptake in 17 of 20 benign lesions decreased. The SUVs at 3 hours postinjection were higher than those at 2 hours postinjection in 9 of 14 malignant lesions and in 2 of 5 benign lesions. Malignant lesions showed a higher retention index than benign lesions (mean +/- standard deviation: 12. 36 +/- 13.37 and -7.05 +/- 17.28, respectively; P < 0.0001). Applying an SUV of 2.5 at 1 hour postinjection with the cut-off value for the differentiation between malignant and benign lesions caused one false negative result and seven false positive results, with a diagnostic accuracy of 83.0% (39 of 47 patients). However, combining the retention index with the SUV obtained at 2 hours postinjection provided a higher diagnostic accuracy (91.5%; 43 or 47 patients) than the SUV alone. The false negative rate remained constant when the retention index was taken into account. Images at 3 hours postinjection usually were unhelpful in differentiating further between malignant lesions and benign lesions. CONCLUSIONS: The current data suggest that delayed FDG-PET scanning at 2 hours postinjection may contribute to differentiation between malignant and benign lesions in the pancreas.

Adult↗
PubMed2000

Caveolin-3 deficiency causes muscle degeneration in mice.

Caveolin-3 is a muscle-specific protein integrated in the caveolae, which are small invaginations of the plasma membrane. Mutations of the caveolin-3 gene, localized at 3p25, have been reported to be involved in the pathogenesis of limb-girdle muscular dystrophy (LGMD1C or caveolinopathy) with mild clinical symptoms, inherited through an autosomal dominant form of genetic transmission. To elucidate the pathogenetic mechanism, we developed caveolin-3-deficient mice for use as animal models of caveolinopathy. Caveolin-3 mRNA and its protein were absent in homozygous mutant mice. In heterozygous mutant mice, both the mRNA and its protein were normal in size, but their amounts were reduced by about half. The density of caveolae in skeletal muscle plasma membrane was roughly proportional to the amount of caveolin-3. In homozygous mutant mice, muscle degeneration was recognized in soleus muscle at 8 weeks of age and in the diaphragm from 8 to 30 weeks, although there was no difference in growth and movement between wild-type and mutant mice. No apparent muscle degeneration was observed in heterozygous mutant mice, indicating that pathological changes caused by caveolin-3 gene disruption were inherited through the recessive form of genetic transmission.

Animals↗
PubMed2000

A sarcoglycan-dystroglycan complex anchors Dp116 and utrophin in the peripheral nervous system.

The dystrophin-associated membrane-integrated protein complex anchors dystrophin in the sarcolemma of striated muscles and is composed of two glycoprotein subcomplexes, the dystroglycan and the sarcoglycan (SG) complexes, and a small membrane protein termed sarcospan (SPN). The SG complex consists of four transmembrane glycoproteins, alpha-SG, beta-SG, gamma-SG and delta-SG. We found that beta-SG and delta-SG were co-expressed with epsilon-SG, a alpha-SG homolog, in the peripheral nerve, but not with alpha-SG or gamma-SG. SPN, which tightly links to the SG complex in the muscle cell membrane, was absent in the peripheral nerve. These peripheral nerve SGs were colocalized at the outermost layer of the myelin sheath of nerve fibers together with the dystroglycan complex, utrophin, and a short dystrophin isoform (Dp116). Immunocytochemical analysis using SG-deficient animals showed that a defect in beta- or delta-SG led to a great reduction of all residual SGs, but not of the other proteins, i.e., dystroglycans, Dp116 and utrophin, in the peripheral nerve. This observation suggests that the epsilon-, beta- and delta-SG molecules form a complex behaving as a single unit similar to the SG complex in muscle cells. An immunoprecipitation study indicated that the SG complex is associated with the dystroglycan complex and Dp116 or utrophin. These results demonstrated that Dp116 and utrophin are anchored to a novel membrane protein architecture, which consists of the SG and dystroglycan complexes, but not SPN, in the Schwann cell membrane.

Animals↗
PubMed2000

Analysis of the clinical benefit of intraoperative radiotherapy in patients undergoing macroscopically curative resection for pancreatic cancer.

PURPOSE: To determine the survival of pancreatic cancer patients treated with intraoperative radiotherapy (IORT) and/or external beam radiation therapy (EBRT) following macroscopically curative resection. METHODS AND MATERIALS: One hundred and thirty-eight patients with pancreatic cancer who had undergone potentially curative total or regional pancreatectomy between 1980 and 1997 were retrospectively analyzed. Among the 138 patients, 98 had a pathologically negative surgical margin and the remaining 40 patients had a positive surgical margin. The usual EBRT dose was 45-55 Gy with a daily fraction of 1.5-2.0 Gy. The median IORT dose was 25 Gy in a single fraction. RESULTS: The 2-year cause-specific survival rate of patients with pathologically negative surgical margins was 19%, and that of patients with positive margins was 4% (p < 0.005). Although the median survival time (MST) of patients with negative margins treated with IORT and EBRT was significantly longer than that of those treated with operation alone (17 vs. 11 months), no significant difference in survival curves was observed. In patients with positive surgical margins in peripancreatic soft tissue, the difference between the survival curve of patients treated with surgery alone and that of those treated with surgery and radiation therapy was borderline significant (p < 0.10). Patients receiving intraarterial or intraportal infusion chemotherapy had significantly improved survival rates compared with those who did not receive it (p < 0.05). CONCLUSION: Although the MST was longer in patients with negative margins receiving IORT and EBRT than in those receiving no radiation, improved long-term survival by IORT and/or EBRT was not suggested. In patients with positive margins, our results obtained by IORT/EBRT were encouraging. Randomized studies with much higher patient numbers are necessary to define the role of IORT in curatively resected pancreatic cancer.

Adult↗
PubMed2000

Inhibition of pRb phosphorylation and cell cycle progression by an antennapedia-p16(INK4A) fusion peptide in pancreatic cancer cells.

In this study, we examined whether or not a small peptide derived from p16(INK4A) protein with the antennapedia carrier sequence could inhibit the growth of pancreatic cancer cells through the inhibition of cell cycle progression. Growth inhibition by the p16-derived peptide was observed in a time- and dose-dependent manner in AsPC-1 and BxPC-3 cells (p16-negative and pRb-positive), whereas Saos-2 cells (p16-positive and pRb-negative) showed no inhibitory effect. In AsPC-1 and BxPC-3 cells, the proportion of cells in the G(1) phase markedly increased 48 h after treatment with 20 microM p16-derived peptide. Cell-cycle analysis of Saos-2 cells showed little change during the entire period of treatment. Immunoblot analysis showed inhibition of pRb phosphorylation after treatment of BxPC-3 with 10 microM p16 peptide. Furthermore, the p16 peptide caused a decrease in cyclin A at later times of treatment. These results demonstrate that the p16-derived peptide can inhibit the growth of p16-negative and pRb-positive pancreatic cancer cells by means of G(1) phase cell cycle arrest resulting from the inhibition of pRb phosphorylation. Restoration of p16/pRb tumor-suppressive pathway by re-expression of p16(INK4A) may play a therapeutic role in the treatment of pancreatic cancer.

Amino Acid Sequence↗
PubMed2000

Transgenic expression of cecropin B, an antibacterial peptide from Bombyx mori, confers enhanced resistance to bacterial leaf blight in rice.

The short persistence of cecropin B peptide in plants, due to post-translational degradation, is a serious impediment in its effective utilization for developing bacterial resistance transgenic plants. Two DNA constructs encoding the full-length precursor of cecropin B peptide and the mature sequence of cecropin B peptide preceded by a signal peptide derived from rice chitinase gene were transformed in rice. The differences in the transcriptional levels in independent transgenic lines showed moderate to high expression of cecropin B gene that correlated well with the differences in cecropin B accumulation observed by Western blot analysis. The development of lesions resulting from infection by Xanthomonas oryzae pv. oryzae was significantly confined in the infected leaflet of transgenic lines, when compared with the control plants.

Animals↗