Biomedical subjects

M Imamura

Publications and source records attributed to M Imamura.

At least 829 records · Page 46Linked to original sources

PubMedDate not supplied

Elevated serum c-erbB-2 protein levels in patients with pancreatic cancer: correlation to metastasis and shorter survival.

Overexpression of the c-erbB-2 proto-oncogene has been shown to correlate with relapse and poor prognosis in adenocarcinomas of the breast and stomach. In pancreatic cancer, c-erbB-2 overexpression has been demonstrated using immunohistochemistry, but the relationship between serum c-erbB-2 level and clinical data has not been fully evaluated. In this study, serum c-erbB-2 protein levels were measured in 100 patients with pancreatic adenocarcinomas and in 9 patients with mucin-producing tumors. Immunohistochemical studies for c-erbB-2 protein were performed in 36 patients and 4.0 U/ml in healthy controls (p < 0.001). The positive rate for serum c-erbB-2 was 34% (37/109) in patients with pancreatic cancer and 0% (0/66) in patients with gallstones and in healthy controls (p < 0.001). Immunohistochemical study disclosed that the positive staining rate was 28% (8/29) in common ductal adenocarcinoma specimens, 43% (3/7) in metastasis specimens, and 75% (3/4) in mucin-producing tumor specimens. Clinical evaluation revealed that 59% (22/37) of serum c-erbB-2-positive patients and 33% (24/72) of negative patients had liver or peritoneal metastases (p < 0.01). The mean survival time was 154 days in the c-erbB-2-positive group and 220 days in the negative group (p < 0.05). We suppose that c-erbB-2 is related to metastasis and progression of the disease in patients with advanced pancreatic cancer.

Adenocarcinoma, Mucinous↗

PubMedDate not supplied

Localization of the bronchodilatory effects of isoproterenol and aminophylline in patients with bronchial asthma: an investigation using selective alveolobronchography.

The effect of isoproterenol (isoprenaline) and aminophylline on airway calibre in 18 adult patients with bronchial asthma was measured directly using selective alveolobronchography. Isoproterenol caused a significant dilation in the maximal calibre of the central airway from bifurcation numbers 1-5 (P < 0.05) and number 6 (P < 0.01). There was no change in bifurcation number 0 (trachea). Aminophylline caused a significant dilatation in bifurcation numbers 3 and 4 (P < 0.01), with no change in bifurcation numbers 0-2 and 5-6. In the minimal calibre of the central airway, both drugs displayed a significant dilatory effect only at bifurcation number 3 (P < 0.05). These results indicate that the central airway is the main site of the dilatory effects of these drugs. Although their precise mechanisms of action are not known, these results suggest that mechanisms of action of the two drugs are different. Isoproterenol acts on the whole region of the central airway, while the action of aminophylline tends to be limited to bifurcation numbers 3 and 4.

Adult↗

PubMedDate not supplied

New technique for mediastinal temperature measurement in hyperthermic cancer treatment: balloon catheter in the azygos vein.

The temperature in the mediastinum during hyperthermia is difficult to determine accurately. We measured the temperature in the azygos vein, using a new technique, and compared the measurements with temperatures in the oesophagus. Eight patients with mediastinal tumours resulting from lung cancer or oesophageal cancer were given hyperthermo-radiotherapy. The temperatures in the azygos vein and in the oesophagus were measured before and during blockage of the blood flow of the azygos vein using an angiographic balloon catheter. None of the patients had complications as a result of these procedures, and hyperthermia by capacitative heating was safely performed. The temperature in the azygos vein increased by a mean of 1.7 degrees C (0.2-2.8 degrees C) after blockage of the blood flow. The temperature in the oesophagus was 0.83 +/- 1.09 degrees C (mean +/- SD) higher than that in the azygos vein. Measurement of the temperature in the azygos vein gives a more accurate estimate of mediastinal temperature than does oesophageal temperature but it is an invasive procedure.

Adenocarcinoma↗

PubMedDate not supplied

Distribution of the carbohydrate antigens, DU-PAN-2 and CA19-9, in tumors of the lung.

AIMS AND BACKGROUND: The carbohydrate chains of malignant cells appear to be related to oncofetal differentiation. The serum levels of CA19-9 have been reported to be evaluated in some patients with lung carcinomas, however, the distribution of carbohydrate antigens were not precisely described. We have investigated in this study the distribution of DU-PAN-2 and CA19-9 antigens in lung tumors. METHODS: Ninety five specimens of lung tumors were selected from surgical specimens. The expression of DU-PAN-2 and CA19-9 were studied by immunohystochemical techniques. The relationship between the expression of these antigens and the classification or the differentiation degree of the tumors were examined. RESULTS: DU-PAN-2 or CA19-9 antigens were detected in 41 (54%) and 45 (59%) cases of the 76 malignant epithelial tumors investigated. These antigens were detected in all types of malignant epithelial tumors, including squamous cell carcinomas, where they were mainly localized to the entire cell surface of malignant cells. In adenocarcinomas, large cell carcinomas and small cell carcinomas, however, these antigens were commonly detected both on the cell membrane and in the cytoplasm. There was positive correlation between the degree of differentiation and DU-PAN-2, but not CA19-9 expression. Among the non-epithelial tumors investigated, those antigens were detected in pulmonary blastomas but not in mesotheliomas. CONCLUSIONS: Immunohistochemical studies for DU-PAN-2 and CA19-9 are useful for defining characteristics of the lung tumors. DU-PAN-2 could be a marker for differentiating between malignant epithelial tumors and mesotheliomas.

Adenocarcinoma↗

PubMedDate not supplied

Modified subcutaneous tissue with neovascularization is useful as the site for pancreatic islet transplantation.

The success rate of subcutaneous transplantation of pancreatic islets has been extremely low. Insufficient oxygen supply to the grafted islets is one possible major obstacle to the preservation of graft function. This study attempted to use basic fibroblast growth factor (bFGF) in subcutaneous transplantation to induce neovascularization and a sufficient blood flow around the space formed for grafted islets in the subcutaneous tissues. A bFGF-releasing device was designed enclosing bFGF in a polyethylene terephthalate mesh bag coated with polyvinylalcohol hydrogel. In the vascularized group (n = 5), two bFGF-releasing devices were implanted bilaterally into the subcutaneous tissue of the back of streptozotocin-induced diabetic Lewis rats. One week after implantation, isolated rat islets (5000) were syngeneically transplanted subcutaneously after the removal of the devices. In the control group (n = 5), no devices were implanted and the same number of rat islets was transplanted directly. One week after the implantation of the devices into the test animals, a thick, well-vascularized capsule was observed in the subcutaneous site. All vascularized recipient rats showed significant decreases in nonfasting blood glucose and maintained normoglycemia for more than 1 month after islet transplantation. However, in the control group, all rats failed to achieve normoglycemia after transplantation. This study provides evidence that the subcutaneous tissue is a promising site for pancreatic islet transplantation, offering convincing advantages in acceptability for diabetic recipients. Establishment of this subcutaneous islet transplantation technique will afford some new perspectives on successful clinical islet transplantation.

Animals↗

PubMedDate not supplied

Subcutaneous xenotransplantation of hybrid artificial pancreas encapsulating pancreatic B cell line (MIN6): functional and histological study.

The biohybrid artificial pancreas is designed to enclose pancreatic tissues with a selectively permeable membrane that immunoisolates the graft from the host immune system, allowing those endocrine tissues to survive and control glucose metabolism for an extended period of time. The pancreatic B cell line MIN6 is established from a pancreas B cell tumor occurring in transgenic mice harbouring the human insulin promoter gene connected to the SV40 T-antigen hybrid gene. It has been proven that glucose-stimulated insulin secretion in MIN6 cells retains a concentration-dependent response similar to that of normal islets. In this study, we performed the histological and functional examination of three-layer microbeads employing MIN6 cells after subcutaneous xenotransplantation to evaluate this device as bioartificial pancreas. MIN6 cells were microencapsulated in three-layer microbeads formulated with agarose, polystyrene sulfonic acid, polybrene, and carboxymethyl cellulose. Microbeads were xenogenically implanted in the subcutaneous tissue of the back of Lewis rats with streptozotocin-induced diabetes. One week after implantation, microbeads were retrieved and cultured for 24 h before the static incubation. There was no evidence of adhesion to the graft and the fibrosis in the transplantation site as determined by gross visual inspection. Microscopic examination demonstrated that retrieved microbeads maintained normal shape, containing intact MIN6 cells. Histological study showed that these MIN6 cells in the microbeads appeared to be viable without cellular infiltration within or around the microbeads. Immunohistochemical analysis of the microbeads clearly revealed the intense staining of insulin in the cytoplasm of encapsulated MIN6 cells. Insulin productivity of MIN6 cells in the microbeads is strongly suggested to be preserved. In response to 16.7 mM glucose stimulation, static incubation of microbeads 1 wk after implantation caused the 2.3 times increase in insulin secretion seen after 3.3 mM glucose stimulation (84.3 +/- 10.0 vs. 37.4 +/- 10.7 microU/3 x 10(6) cells/hr, n = 5 each, p < 0.01). This study demonstrates that three-layer microbeads encapsulating MIN6 cells retain excellent biocompatibility and maintain good insulin secretion even after subcutaneous xenotransplantation, suggesting the possible future clinical application of this unique bioartificial pancreas to subcutaneous xenotransplantation.

Animals↗

PubMedDate not supplied

Prolonged effect of troglitazone (CS-045) on xenograft survival of hybrid artificial pancreas.

Troglitazone (CS-045), a thiazolidinedione derivative, is a new oral antidiabetic agent that enhances insulin sensitivity and improves insulin responsiveness. In this study we examined the effects of CS-045 on the survival of xenografted bioartificial pancreas. Isolated rat islets were microencapsulated with three-layer agarose microcapsules (polybrene, carboxymethyl cellulose, and an agarose-polystyrene sulfonic acid mixture). Diabetes was induced by intraperitoneal injection of streptozotocin 220 mg/kg. Recipient diabetic mice were separated into two groups. In the CS-045 treated group, the recipient mice were given feed mixed with CS-045 (0.2% w/w) starting from 1 wk before transplantation up to graft failure. The mice in the control group had feed without CS-045. Three hundred microencapsulated rat islets were xenotransplanted into the intraperitoneal cavity of each recipient mouse in both groups. One month after xenotransplantation, IVGTT was performed for all recipients. Xenotransplantation of 300 rat islets in microcapsules decreased the nonfasting blood glucose levels of both groups within 2 days. In the CS-045-treated group (n = 3), the normoglycemic period lasted for more than 1 mo without administration of immunosuppressive drugs (45 +/- 4.3 days). However, in the control group (n = 4), the blood glucose levels of all recipients were already elevated on day 4. In the IVGTT study, the glucose assimilation was markedly and significantly better in the CS-045-treated group than in the control group (K = 1.7 +/- 0.1 vs. 0.7 +/- 0.28 respectively, p < 0.01). This study demonstrates that a newly developed oral antidiabetic agent, CS-045 could favorably ameliorate the diabetic state of the recipients xenotransplanted with the bioartificial pancreas, leading to an improved glucose tolerance and longer xenograft survival.

Animals↗

PubMedDate not supplied

Improved large-scale isolation of breeder porcine islets: possibility of harvesting from nonheart-beating donor.

To establish a large-scale isolation procedure for adult porcine islets usable as a donor source for xenotransplantation and as a model of human islet isolation, we improved several characteristics of the conventional isolation procedure. At a slaughterhouse we first selected a breeder pig over 1.5 years old (and over 200 kg in weight) with warm ischemic time (WIT) of 15 +/- 2 minutes as nonheart-beating donors. Then, we made a special enzymic mixture that consisted of collagenase S-1 (260 U/mg, NittaZelatin, Japan), collagenase P (1.86 U/ml Lyo Boehringer-Mannheim, USA), DNase (Sigma, St. Louis, Mo), Disparse (NittaZelatin, Japan), and protease inhibitor (Sigma). Third, this mixture was injected very gently into the pancreatic duct at the time of pancreatic harvesting. To prevent overdigestion of the pancreas, the mixture was first cooled to less than 10 degrees C. Fourth, during the warm digestion of pancreas, the pancreas with the enzymic mixture was quietly put in a water bath at 37 degrees C without mechanical shaking. Fifth, we purified the islets with a COBE 2991 cell processor by the Dextran 70 gradient method, because Dextran 70 is very cheap and has the same purification effect as the Ficoll gradient. The results of 10 consecutive breeder porcine islet isolations are reported. The total yield of isolations of islets over 50 microm in the longest diameter after staining with Dithizone (DTZ) was 85,900 +/- 19,954 islets, 291,667 +/- 240,452 IEQ (2,900 +/- 2,324 IEQ/g). The purity of the isolated islets was very high: 90.2 +/- 3.8%. Glucose stimulation during in vitro incubation induced significant insulin release from isolated breeder porcine islets. In two of the diabetic rats receiving encapsulated islets grafts using a mesh-reinforced polyvinyl alcohol hydrogel bag (MRPB), a prominent reduction in serum glucose levels (less than 200 mg/dL) persisted for 13 and 19 days, respectively, after intraperitoneal xenotransplantation islets without immunosuppression. In conclusion, we succeeded in a more efficient and less-expensive isolation of a large amount of adult porcine islets from a nonheart-beating donor.

Animals↗

PubMedDate not supplied

Effect of a new immunosuppressive agent, FTY720, on survival of islet allografts.

A newly developed immunosuppressant, FTY720, has a unique mechanism that is quite different from those of conventional immunosuppressants, and is presumed to be mediated through decreases in the number of peripheral lymphocytes, especially helper T cells. This study was performed to ascertain whether this innovative drug could prolong islet allograft survival. The donors were inbred Lewis rats and the recipients were ACI rats rendered hyperglycemic with intravenous streptozotocin. In the study group, FTY720 dissolved in distilled water was orally administered at a dose of 5 mg/kg to the recipient ACI rats 1 day before and on the day of grafting. In the control group, only distilled water was orally administered to the recipient ACI rats on the day before and the day of grafting. Two thousand islets were transplanted into the portal vein of the recipient rats in the study and control groups immediately after isolation. The graft survival time in the study group was significantly longer than that in the control group, indicating that FTY720 retains a potent effect on the prolongation of islet allograft survival. FTY720 could become a useful immunosuppressant for future clinical islet allotransplantation.

Animals↗

PubMedDate not supplied

Novel method for isolation of adult porcine pancreatic islets with two-stage digestion procedure.

It is particularly difficult to isolate porcine islets (PI). Experience suggests that the success rate of porcine islet isolation (PII) is probably considerably influenced by the distension and digestion of the pancreas. In this study, we divided the digestion procedure into two stages and developed a new enzyme solution to improve both the distension and digestion procedures. As a result, we established a novel and stable method of large-scale adult porcine islet isolation (APII). The harvested pancreata of 2-year-old pigs weighing over 200 kg (n = 18) were distended by introducing our new enzyme solution gently and slowly through the pancreatic ducts. Two-stage digestion (cold, then warm) was then performed by first placing the distended pancreata on ice for 2 h to cause diffusion of the enzyme solution around the islets, and then by incubating the pancreata in a water bath at 37 degrees C for 45 min without shaking. The islets were purified by a COBE 2991 cell processor on dextran T70 discontinuous density gradients. Histological study was performed on porcine pancreata sampled after 0, 15, 30, and 45 min of the second stage, and stained with H&E stain. Next, islet equivalent was calculated. Static incubation study was performed by stimulating the islets with 3.3 and 16.7 mM glucose in Krebs' Ringer bicarbonate buffer (KRBB) solution at 37 degrees C for 1 h, and finally the insulin released was measured. The dilated acinar cells septa around the islets were observed at time 0. Destruction of the acinar cells around the islets by warm digestion was recognized at 15 and 30 min, and destroyed and separated acinar cells present around the islets at 45 min. During the entire course of the warm digestion, the islets remained intact. The number of isolated islets was 291,667 +/- 240,452 IEQ/pancreas (n = 14) and 3,294 +/- 2199 IEQ/g of pancreatic tissue. The purity of recovered porcine islets was over 90%. The concentration of the insulin secreted by 10,000 IEQ islets selected at random was 83.9 +/- 13.4 microU/dish/h in response to 3.3 mM glucose and 104.1 +/- 12.9 microU/dish/h in response to 16.7 mM glucose (n = 20). A success rate of approximately 80% was attained with APII. We demonstrated that this increase in the success rate was due to the improved distension and digestion provided by this method. This two-stage APII method with its new enzyme solution may facilitate the future use of porcine islets in clinical xenotransplantation trials.

Animals↗

PubMedDate not supplied

Podometry: a critical evaluation of its use in Hansen's disease.

The aim of this paper is to evaluate the effectiveness of podometry to measure the pressure developed over the feet and the value of these findings to help in the prevention of the plantar neuropathic ulcer in patients bearing Hansen's disease. We evaluated 13 patients with impaired plantar pain and touch sensations and 17 normal patients. All the patients were submitted to static evaluation using the podometer. The system employed was the "Midcapteur" commercial podometer composed of a platform for acquisition of analogic data capable of registering the segmental pressures applied to the feet. These data are read by a 386 IBM/PC compatible computer that registers the graphic patterns obtained from the pressures developed and also calculates the modes of pressure distribution in the four quadrants of the foot. These data obtained by means of static podometry were compared to the clinical evaluation of pain and touch sensation of the feet in hansenian patients. The results demonstrate that podometery is an efficient method for evaluating the pressure in impaired feet in Hansen's disease and is a progression of neuropathic ulcer; it is sensitive in the identification of the spots of increased pressure in anesthetic and anomalous areas, asymmetries and in correlating the presence of ulcers with increased pressure.

Adult↗

PubMedDate not supplied

The use of a hypoxic cell radiosensitizer AK-2123 gave no improvement in thermoradiotherapy combined with hydralazine.

An electron-affinic compound, AK-2123, and the anti-hypertensive agent, hydralazine, were combined with radiation and hyperthermia for treatment of murine SCC-VII tumours. Hydralazine markedly decreased tumour perfusion while AK-2123 had no influence on it. Hydralazine enhanced the tumouricidal effects of hyperthermia alone and in combination with radiation. AK-2123 provided a radiosensitization which was significant only in tumours irradiated without supplementary hyperthermia. The greatest tumour response was achieved when thermoradiotherapy was combined with hydralazine alone; the additional use of AK-2123 with this treatment combination did not further increase the effect. It is concluded that hydralazine plus heat virtually eliminated a hypoxia-related radioresistance in tumours, thus removing the requirement for AK-2123 administration.

Animals↗

PubMedDate not supplied

Multidetector-row CT analysis of time-dependent changes in lung fields after chest irradiation: usefulness of precision scans.

Time-dependent changes in lung fields after chest irradiation were analyzed using multidetector-row CT. Routine scans at 3-mm raw thickness and 8-mm recon thickness and precision scans at 0.5-mm raw thickness and 0.5-mm recon thickness were compared with respect to the number of each finding and the time-dependent changes in the rate of each finding. Among the findings visualized by these scans, ground-glass opacity (GGO) showed the highest overall appearance rate. Precision scans exceeded routine scans in the rates of all findings except GGO and confluent shadows, and the two types of scans showed the greatest difference in the rate of GGO. Since we found that GGO tended to be overestimated on routine scans, we confirmed it by a phantom experiment. Precision scans were similar or superior to routine scans in the rates of findings except 3 months after irradiation. We consider that the concomitant use of precision scans is useful in that it allows more accurate evaluation of various post-irradiation changes in lung fields including GGO, in which the lesion is in a reversible stage.

Aged↗

PubMedDate not supplied

Analysis of cell kinetics after irradiation by flow cytometry: proliferative ability of G2-blocked cells after cell sorting.

Irradiation, dose-dependently, increases the percentage of cells in the G2 + M phase and the duration of cell cycle arrest, reflected by changes in cell kinetics in the first 48 h. Cells in the G2 + M phase are considered radiosensitive but little is known about their proliferative ability. We studied proliferative ability of irradiated G2 phase-arrested cells following flow cytometric cell sorting using fluorescent Hoechst 33342 staining. Although proliferative ability of non-irradiated cells was not different between G1 and G2 + M phases, cells arrested in G2 + M after irradiation, especially at higher doses, showed less ability than cells in G1. Proliferative ability also correlated well with of G2 block duration.

Benzimidazoles↗

PubMedDate not supplied

Studies on hyperthermia combined with arterial blockade for treatment of tumors: (Part I) effectiveness of hyperthermia combined with arterial ligation.

Arterial ligation was combined with hyperthermia in rabbits with VX2 tumors implanted in the leg. For seven days after arterial ligation, blood flow was decreased and the pH was low in both normal muscle and tumor tissue. The temperature of normal muscle and tumor tissue increased faster and reached a higher level on heating immediately after ligation than without ligation. The antitumor effect of hyperthermia was stronger immediately after ligation than two or seven days afterwards. However, damage to normal muscle was severe with this combination therapy, so a better method of therapeutic arterial blockade is needed.

Animals↗

PubMedDate not supplied

Studies on hyperthermia combined with arterial blockade for treatment of tumors: (Part II) effectiveness of hyperthermia combined with arterial embolization using degradable starch microspheres.

The efficacy of temporary arterial embolization using degradable starch microspheres combined with hyperthermia was investigated in rabbits bearing VX2 tumors. Microsphere injection caused a marked decrease of tumor blood flow and pH. During heating, there was a marked increase of the maximum temperature in tumor tissue compared with normal muscle. Tumor growth was suppressed 330% times at 3 weeks after hyperthermia alone and 270% times following combined treatment with microspheres and hyperthermia. Damage to normal muscle tissue was mild. In conclusion, this combination therapy may be useful for causing selective tumor damage and reducing the effect on normal tissues.

Animals↗

PubMedDate not supplied

Studies on hyperthermia combined with arterial therapeutic blockade for treatment of tumors: (Part III) effectiveness of hyperthermia combined with arterial chemoembolization using degradable starch microspheres on advanced liver cancer.

Arterial chemoembolization using degradable starch microspheres and adriamycin was combined with hyperthermia to treat advanced liver cancer. The prolonged peak adriamycin level in hepatic venous blood suggested that the drug persisted for longer in the liver after injection containing microspheres. Heating efficiency was increased more in tumor tissue than in normal liver tissue after embolization. This combined therapy was performed in eight patients with advanced liver cancer and was effective in three (complete or partial remission). The mean survival time was 25 weeks and there were no severe side effects. This combined therapy may be useful for liver cancer.

Aged↗

PubMedDate not supplied

Change of temperature in mouse tumour tissue immersed in a water bath at 44 degrees C.

We investigated the change in temperature in tumour and normal tissues of mice when immersed in a water bath at 44.0 degrees C as part of a series of studies of hyperthermia. The right hind legs of the mice bearing the experimental tumour sarcoma 180 were immersed in the water bath, and measurements were performed using the multi-thermocouple thermosensor from a radiofrequency (RF) generator every 24 sec with a precision of 0.1 degrees C. The temperature in all tumour tissues exceeded 43.0 degrees C only at 1 min 24 sec after immersion of the limbs. The rise in temperature then reached a plateau phase, and was maintained around 44.0 degrees C. However, we found that the temperature of the normal tissue was about 0.6 degrees C lower than that of the tumour tissue or the tissue around the tumour at the plateau phase.

Animals↗