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Biomedical subjects

K Sugimachi

Publications and source records attributed to K Sugimachi.

At least 343 records · Page 19Linked to original sources
PubMed1997

Dose intensity of uracil and tegafur in postoperative chemotherapy for patients with poorly differentiated gastric cancer.

A retrospective analysis of postoperative chemotherapy had shown the continuous administration of UFT, an oral preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil at a molar ratio of 1:4, to be effective for poorly differentiated gastric cancer. We therefore sought to determine prospectively the effective dose of postoperative chemotherapy with UFT for patients with poorly differentiated gastric cancer following a curative resection. We determined the effect of the combined intravenous administration of mitomycin C (MMC) and oral treatment with protein-bound polysaccharide Kreha (PSK), extracted from the basidiomycete Coriolus versicolor, and UFT at a dose of either 8 mg/kg or 12 mg/kg daily for 1 year. A total of 224 patients with poorly differentiated stage II-IV gastric cancer were entered into this study after undergoing a curative resection. No differences were observed between the two treatment groups in terms of prognostic factors, the toxicity rate or the doses of the drugs prescribed, other than UFT. The higher dose of UFT in maintenance therapy led to a decrease in the recurrence rate (P < 0.05), and increases in disease-free survival and cause-specific survival (P < 0.05). UFT at 12 mg/kg in postoperative chemotherapy was thus found- to improve the postoperative results with no increase in toxicity for poorly differentiated gastric cancer, and is also cost-effective for outpatients.

Adult↗
PubMed1997

Laparoscopic splenectomy for splenic hamartoma.

Advances in imaging techniques have made pre-operative diagnosis of splenic tumors possible. A case of successful laparoscopic splenectomy for splenic hamartoma is described here and the indications of this technique are discussed.

Hamartoma↗
PubMed1997

Needle and trocar injury during laparoscopic surgery in Japan.

BACKGROUND: With the growth and sophistication of laparoscopic surgery, increased attention is now being focused on safety and complications. METHODS: In an attempt to address questions regarding the safety of laparoscopic surgery, a retrospective study of the time period from January 1991 to December 1995 was conducted by the Study Group of Endoscopic Surgery in Kyushu, Japan. RESULTS: The response rate was 84.4% (152 of 180 hospitals). During the last 5 years 17,626 patients underwent endoscopic operations and 87.5% (15, 422 patients) had laparoscopic surgery while 12.5% (2,204 patients) underwent thoracoscopic surgery. In 96.6% of the hospitals a minimal open laparotomy was used. Among the various operations, a cholecystectomy was performed in the largest number of patients (13, 787). The total number of complications was 415 (2.7%), of which 156 (37.6%) were related to needle or trocar insertion. Visceral injury was found in 22 patients (0.14%): major vessel injury in 10, gastrointestinal tract injury in 11, and liver injury in one patient. Abdominal wall injury was seen in 79 patients (0.52%), bleeding in 70 (0.46%), and a hernia in 9 (0.06%). Extraperitoneal insufflation occurred in 55 patients (0.36%). There was no mortality. The complication rate significantly decreased year by year after the use of laparoscopic surgery began. CONCLUSIONS: The most common complications of laparoscopic surgery are related to needle and trocar insertion. These are preventable by placement under direct vision with verification of the intraperitoneal location of the needle and trocar.

Abdomen↗
PubMed1997

Down-regulation of endothelin B receptors in autogenous saphenous veins grafted into the arterial circulation.

OBJECTIVES: It has been postulated that endothelin (ET) might be involved in the development of atherosclerotic vascular lesions. The present study was done to characterize changes in the contractility and ET receptor subtypes in the autogenous saphenous vein graft (VG). METHODS: The rabbit saphenous vein (SV) was grafted into the ipsilateral femoral artery (FA), and at 4 weeks after the operation, VG was harvested. In the medial layer samples of SV, VG and FA, the cytosolic Ca2+ concentration ([Ca2+]i) and force were monitored using front-surface fluorometry of fura-PE3, and mRNA expression of ET receptors was evaluated using the reverse transcription polymerase chain reaction. RESULTS: ET-1 (10(-7) M) developed force in SV, VG and FA, to the same extent. Sarafotoxin (S6c; 10(-7) M) developed force in the SV to the same extent as ET-1. However, S6c did not develop force in FA, and slight force developed in VG. Contractions induced by ET-1 were associated with increases in [Ca2+]i. FA expressed ETA receptor mRNA predominantly, and SV expressed both ETA and ETB receptors mRNAs. In VG, the expression of ETB receptor mRNA was markedly reduced, but expression of ETA receptor mRNA remained unchanged. CONCLUSIONS: Functioning ETB receptors and their mRNA are down-regulated when veins are grafted into the arterial circulation. All these changes in gene expression and function are part of adaptive responses known as 'arterialization'.

Animals↗
PubMed1997

L-arginine inhibits smooth muscle cell proliferation of vein graft intimal thickness in hypercholesterolemic rabbits.

OBJECTIVE: The effect of the chronic administration of L-arginine on intimal thickness and the kinetics of smooth muscle cell proliferation in autovein grafts in hypercholesterolemic rabbits were examined. METHODS: Male rabbits were fed a 1% cholesterol diet (control group) and a 1% cholesterol diet supplemented by 2.25% L-arginine HCl in drinking water (arginine group). Each group underwent reversed autologous vein bypass grafting of the left common carotid artery using the left external jugular vein. At 2 or 4 weeks after operation, intimal cell proliferation was determined by 5-bromo-2'-deoxyuridine (BrdU) incorporation and intimal thickness of the graft was measured with an ocular cytometer. At 4 weeks after operation, endothelium-dependent responses were examined by isometric tension recording. RESULTS: At 4 weeks after operation, the level of plasma arginine and citrulline are significantly higher in the arginine group (n = 7), compared with the control (n = 7). Intimal thickness in the arginine group (n = 7) was significantly reduced, compared with that of the control (n = 7). At 2 weeks after operation, the BrdU labeling index of the control (n = 5) was significantly higher than that of the arginine group (n = 5). At 4 weeks after operation, ACh caused endothelium-dependent relaxation in the arginine group (n = 4), while in the control (n = 4), ACh did not relax. CONCLUSIONS: These results suggest that smooth muscle cell proliferation of the rabbit jugular vein grafts during hypercholesterolemia occurs at an early stage after graft implantation, prior to the development of intimal thickness. Intimal thickness of vein graft during hypercholesterolemia was reduced by chronic administration of dietary L-arginine, by inhibiting smooth muscle cell proliferation. The enhancement of NO production in the blood vessel wall may therefore be useful for preventing late graft failure.

Acetylcholine↗
PubMed1997

Relationship between early recurrence and micrometastases in the lymph nodes of patients with stage I non-small-cell lung cancer.

OBJECTIVE: This retrospective study was designed to detect occult micrometastases in the lymph nodes with the use of monoclonal anti-cytokeratin reagent, which is specific for epithelial cells but not for lymphocytes or plasmacytes, as well as to assess the relationship between the presence of occult micrometastases in the lymph nodes and an early relapse in patients with stage I non-small-cell lung cancer. METHODS: The paraffin-embedded sections of 973 regional lymph nodes from 44 patients with stage I non-small-cell lung cancer were studied. We used CAM-5.2 as the primary monoclonal anti-cytokeratin reagent and an indirect staining technique with the streptavidin-biotin-peroxidase complex method. RESULTS: We identified cytokeratin-positive cells in 31 (70.5%) of 44 patients and in 91 (9.4%) of the 973 lymph nodes. Of these 31 patients with cytokeratin-positive cells, 19 and 12 were restaged as having N1 and N2 disease, respectively. Thirteen patients had recurrent disease at 17 sites during the follow-up. Two of these recurrences were in the mediastinal nodes and the other 15 occurred at distant organs. Twelve of the 13 patients had micrometastatic disease in the regional lymph nodes. Disease-free survival duration was significantly shorter in the patients with micrometastases in the mediastinal lymph nodes than in patients with node-negative disease (p = 0.004). The independence of this prognostic significance was demonstrated by a multivariate analysis. CONCLUSION: These findings indicate that the detection of occult micrometastases in the mediastinal lymph nodes with monoclonal antibodies to cytokeratin can thus be used to predict an early relapse in patients with stage I non-small-cell lung cancer.

Aged↗
PubMed1997

Surgical treatment and outcome for node-negative gastric cancer.

BACKGROUND: The clinicopathologic characteristics and prognosis for patients with node-negative gastric cancer have heretofore remained to be determined. METHODS: We analyzed data on 730 of our patients with node-negative gastric cancer who underwent curative gastric resection in the Department of Surgery II, Kyushu University Hospital, between 1965 and 1990, with reference to prognostic factors. The presence of lymph node metastasis was determined by means of routine hematoxylin-eosin staining of excised tissues. RESULTS: The 5-year survival rate was 91.7% and the 10-year rate was 88.5%; thus the prognosis was good for patients with node-negative gastric cancer. When the prognosis was analyzed by stratification of each clinicopathologic factor, the survival time was shorter for older patients when the size of the tumor was larger, when the tumor involved the entire stomach, and when-tissues revealed infiltrative growth, serosal invasion, and lymphatic invasion. Extensive lymph node dissection was performed for 86.6% of the patients, and for these patients the prognosis was better, with a statistical difference. In a multivariate analysis, tumor size, serosal invasion, and extensive lymph node dissection proved to be independent prognostic factors for patients with node-negative gastric cancer. CONCLUSIONS: Prophylactic lymph node dissection for patients with gastric cancer will prolong the survival time.

Adult↗
PubMed1997

Overexpression of endothelin-1 mRNA and protein in portal hypertensive gastric mucosa of rats: a key to increased susceptibility to damage?

BACKGROUND: Portal hypertension predisposes gastric mucosa to increased injury by various noxious factors. Because endothelin-1 (ET-1) is a potent vasoconstrictor that enhances gastric mucosal injury, we examined ET-1 expression in the portal hypertensive (PHT) gastric mucosa and its possible role in increased mucosal susceptibility to damage. METHODS: In gastric specimens of PHT or sham-operated rats, ET-1 mRNA expression was studied by S1-nuclease protection assay and ET-1 protein by enzyme immunoassay and immunostaining. We also determined the extent of ethanol-induced gastric mucosal necrosis in PHT and sham-operated rats after administering either a placebo or FR 139317, a selective ETA receptor antagonist. RESULTS: In PHT stomachs ET-1 mRNA expression and protein concentration were significantly increased compared with sham-operated controls: mRNA expression (ET-1/glyceraldehyde-3-phosphate-dehydrogenase ratio), 0.54 +/- 0.18 versus 0.30 +/- 0.08; protein concentration, 7.36 +/- 2.21 pg/mg versus 3.93 +/- 0.40 pg/mg, respectively; both p < 0.01. Immunofluorescence signal of ET-1 protein was predominantly localized to endothelia of gastric mucosal and submucosal vessels. In PHT stomachs FR 139317 significantly reduced mucosal necrosis (percentage of necrotic area, from 24.9 +/- 5.9% to 10.8 +/- 4.0%; p < 0.01), although it had no effect on sham-operated controls. CONCLUSIONS: Portal hypertension activates the ET-1 gene with overexpression of ET-1 protein in the gastric mucosa. Protection of PHT gastric mucosa by ETA receptor antagonist against damage indicates that overexpression of ET-1 plays an important role in increased susceptibility of PHT gastric mucosa to injury.

Animals↗
PubMed1997

Enhancement of nitric oxide production after arterial reconstruction in patients with arteriosclerosis obliterans.

PURPOSE: Nitric oxide (NO) not only relaxes vascular smooth muscles, but it also reduces platelet adhesion and is itself a potent antiaggregatory substance. Experimental studies have shown that the release of NO is modulated by the blood flow. However, little clinical information is available about the effects of hemodynamic changes after arterial reconstruction on NO production. We therefore examined whether the plasma levels of nitrite (NO2-) and nitrate (NO3-) ions increased after arterial reconstruction in patients with arteriosclerosis obliterans (ASO). METHODS: Blood samples were obtained from the femoral artery in seven patients who underwent arterial reconstruction and seven healthy individuals (control). NO2- and NO3- levels were measured using high-performance liquid chromatography before the operation and 1 hour and 14 days after the operation. In addition, the mean femoral artery blood flow and ankle-brachial pressure index (ABI) were also measured using a duplex and Doppler velocimeter both before and after the operations. RESULTS: In the control subjects, the mean plasma NO2-, NO3-, and NOx (NO2- plus NO3-) levels in the femoral artery were 0.37 +/- 0.15 mumol/L, 45.6 +/- 10.8 mumol/L, and 46.0 +/- 10.9 mumol/L, respectively. Before the operation in the patients with ASO, the mean plasma NO3- (23.8 +/- 2.2 mumol/L) and NOx levels (24.0 +/- 2.3 mumol/L) were significantly lower than those in the control subjects, whereas the plasma NO2- levels (0.27 +/- 0.04 mumol/L) were comparable between the two groups. At 14 days after operation, the mean plasma NO3- and NOx levels in the femoral artery were significantly increased to 42.8 +/- 5.6 mumol/L and 43.4 +/- 5.6 mumol/L compared with those before the operation, whereas the mean plasma NO2- levels (0.50 +/- 0.05 mumol/L) changed significantly. The mean ABI and the mean flow rate before the operation were 0.32 +/- 0.07 and 344 +/- 145 ml/min, respectively. Both the ABI and the mean flow rate significantly increased to 1.04 +/- 0.06 and 627 +/- 141 ml/min after the operation. CONCLUSIONS: In patients who have ASO, the mean plasma level of NO is significantly lower than that of healthy individuals. In patients with ASO, the mean blood flow increased significantly after arterial reconstruction. This hemodynamic improvement may thus enhance NO production and may also help to maintain the patency of the bypass graft or native artery.

Aged↗
PubMed1997

The effect of probucol on intimal thickening of autologous vein grafts in hyperlipidemic rabbit.

Probucol is used to treat hypercholesterolemia and also has an anti-atherogenic effect. The effects of probucol on intimal thickening of autologous vein graft in hyperlipidemic rabbits with poor distal run-off were investigated. A poor distal run-off model was prepared in the right hindlimb of 18 rabbits allocated to four groups depending on diet: normolipidemic commercial diet, (NL group, n = 5); hyperlipidemic diet (HL group, n = 5); commercial diet with 1% probucol (NP group, n = 4); and hyperlipidemic diet with 1% probucol (HP group, n = 4). After 4 weeks the femoral vein grafts were implanted into normal (n = 18) or poor (n = 18) runoff limbs. Vein grafts were harvested 4 weeks after implantation. Intimal thickening of the graft was measured and macrophages therein examined immunohistochemically. The serum cholesterol level was not reduced by probucol treatment. The mean flow rate of the graft was significantly reduced in the poor run-off limb. On histological examination intimal thickening in the poor run-off limb was significantly greater than that of controls, while intimal thickening in the HL and HP groups was enhanced compared with that in the NL and NP groups, respectively. Mean intimal thickening in each limb in HP group rabbits was significantly lower than that in HL rabbits (microm): control (HL/HP): 99.4(7.4)/58.8(0.7) (P < 0.05); poor run-off (HL/HP): 155.3(9.6)/130.3(7.3) (P < 0.O5). There was no difference between NL and NP (microm): control (NL/NP): 44.6(24.7)/31.5(12.8); poor run-off (HL/HP): 115.3(13.8)/97.5(34.0). In addition, enhanced intimal thickening due to poor distal run-off was not suppressed. Immunohistochemical staining showed intimal macrophage infiltration in the HL and HP groups; however, macrophage infiltration in grafts in the HP group was less than in the HL group. In conclusion, under hyperlipidemic conditions, probucol decreased intimal thickening enhancement of the vein graft, and suppressed intimal macrophage infiltration. These findings were similar to the anti-atherogenic effect of probucol in the native artery. Hence, probucol administration after vascular reconstruction with vein grafts in patients with hyperlipidemia may be beneficial.

Animals↗
PubMed1997

Acceleration of impairment of endothelium-dependent responses under poor runoff conditions in canine autogenous vein grafts.

OBJECTIVES: To assess the effects of changes in shear stress on endothelium-dependent responses. MATERIALS AND METHODS: Autologous vein grafts were implanted in poor or normal distal runoff limbs of 10 mongrel dogs. Six weeks after grafting the vein grafts were removed, cut into rings, and suspended in organ chambers for isometric tension recording. RESULTS: The average value of intimal thickening was 110.7 +/- 45.2 microns in poor runoff limbs and 65.5 +/- 27.9 microns in control limbs, respectively. There was a significant difference between the two groups. Acetylcholine caused comparable endothelium-independent contractions in both groups. In the control group, adenosine diphosphate, thrombin and A23187 caused endothelium-dependent relaxations. In the poor runoff group, the endothelium-dependent relaxations caused by adenosine diphosphate and thrombin were impaired, while A23187 caused comparable endothelium-dependent relaxations. Direct relaxations in response to sodium nitroprusside were comparable between the two groups. CONCLUSIONS: This dysfunction of the endothelium under conditions of abnormal flow may accelerate intimal thickening of the vein graft and result in late graft failure.

Animals↗
PubMed1997

Surgical strategy of abdominal aortic aneurysm with preoperative renal failure.

OBJECTIVES: To determine the effect of preoperative renal failure on the outcome of patients suffering from infrarenal abdominal aortic aneurysm (AAA). METHOD: During the period from January 1979 to August 1995, 364 patients with AAA were admitted to our hospital and 323 underwent elective repair. The patients were retrospectively analysed in three groups. Group I was composed of 273 patients with a normal renal function who underwent an aneurysm repair. Group II was composed of 50 patients who demonstrated a preoperative renal dysfunction (creatinine above 2.0 mg/dl or creatinine clearance below 40 ml/min) and underwent an operation, including three patients maintained on chronic haemodialysis. Group III was composed of 18 patients with a renal dysfunction who did not undergo repair, including one patients maintained on chronic haemodialysis. RESULTS: The operative mortality rate of groups I and II were 0.4% and 2.0%, respectively, although no significant difference was observed. The incidence of postoperative cardiac and pulmonary complications were also comparable in two groups. No patients required acute haemodialysis. The 5-year survival rate of group II (44%) was significantly higher than that of group III (20%), and seven of the 18 patients (39%) in group III ultimately died of a rupture of the AAA. CONCLUSIONS: Patients with chronic renal failure can undergo an abdominal aortic aneurysm repair based on the same indications as those without renal failure.

Aged↗
PubMed1997

Expression of MAGE and BAGE genes in Japanese breast cancers.

BACKGROUND: The MAGE and BAGE genes code for distinct antigens, which are recognized on melanoma cells as well as on other various tumor cells by autologous cytolytic T lymphocytes. These antigens may thus constitute useful targets for specific immunotherapy, since no expression of MAGE or BAGE genes has been recognized in normal tissue except for the testis. PATIENTS AND METHODS: We studied the MAGE-1, MAGE-3, and BAGE gene expression observed in 49 Japanese breast cancers. Gene expression was evaluated by reverse transcription polymerase chain reaction. RESULTS: Out of 49 tumor tissue specimens of primary breast cancers, the expression of MAGE-1, -3 and BAGE was recognized in 15 (31%), 12 (24%), and 4 (8%) tumors, respectively. The expression of MAGE and BAGE genes is not recognized in normal breast tissue. The expression of the MAGE-3 gene was frequently recognized in tumors with lymphatic and/or vascular vessel permeations. Either MAGE-1 or -3 gene expressions were induced in 1 of 3 MAGE-1 negative breast cell lines or 1 of 3 MAGE-3 negative breast cell lines by the treatment with 5-aza-2'-deoxycytidine. CONCLUSIONS: These findings suggest that: 1) the identification of such antigens coded by MAGE or BAGE genes may thus offer the possibility of using specific immunotherapy, and 2) the use of a demethylating agent may increase the number of patients who might be candidates for MAGE specific immunotherapy.

Antigens, Neoplasm↗
PubMed1997

K-ras and p53 mutations are an independent unfavourable prognostic indicator in patients with non-small-cell lung cancer.

We examined 159 consecutive cases of non-small-cell lung cancer (NSCLC) for a mutation at codon 12 of the K-ras gene and for a mutation of the p53 gene occurring in exons 5-8. Eleven (6.9%) had mutations of the K-ras (ras+) and 57 (35.8%) had mutations of the p53 (p53+). There were 95 cases (59.7%) with ras- p53-, seven cases (4.4%) with ras+/p53-, 53 cases (33.3%) with ras-/p53+ and four cases (2.5%) with ras+/p53+. The ras+ group had a worse prognosis than the ras group in all cases and in 107 early-stage cases (stage I-II, P<0.05). The p53+ group had a worse prognosis in 107 early-stage cases (P<0.01), but there was no statistically significant difference when 52 advanced-stage cases (stage III-IV) or all patients were considered. Both ras and p53 mutations were unfavourable prognostic factors in 94 cases with adenocarcinoma, but there was no statistical significance in 57 cases with squamous cell carcinoma. According to Cox's model, the pathological stage, ras mutation and p53 mutation were found to be independent prognostic factors. Our results suggest that ras and p53 mutations were independent unfavourable prognostic markers especially in the early stage of NSCLC or in adenocarcinoma.

Adult↗
PubMed1997

Dialysis-related amyloidosis of the tongue in long-term hemodialysis patients.

Dialysis-related amyloidosis (DRA) predominantly occurs in the osteoarticular structures. However, according to studies in the increasing number of long-term hemodialysis patients, DRA has also been systemically found to appear in the other tissues and organs as well. In this study, we investigated lingual amyloidosis in relation to systemic DRA. A total of 472 patients were studied who were on regular hemodialysis for more than 10 years, including 103 patients for more than 20 years. Eight of these patients (7 males and 1 female, mean age 59 +/- 8 years, range 46 to 68 years) developed lingual amyloidosis, seemingly as a result of beta2-microglobulin (beta2m) deposits. All patients demonstrating lingual amyloidosis had been treated with regular hemodialysis for more than 20 years (mean HD duration 23.6 +/- 1.4 years), and its morbidity was 7.8% in the 103 patients and 20% (6 patients) in the 30 patients treated for more than 23 years with hemodialysis. Hemodialysis (HD) duration with bioincompatible unsubstituted cellulose membranes in the 8 patients was longer than that in the control group without lingual amyloidosis (P < 0.05). Lingual amyloid nodules were whitish-yellow in color and varied in size, at least over 1 mm in diameter. Their consistency was firmer than the intact tongue. The location of the amyloid nodules could be classified into two types: (1) diffuse type (diffusely distributed over the tongue), and (2) lateral type (localized only in the lateral side of the tongue). Five of the eight patients with lingual amyloidosis complained of functional disturbances in the tongue, such as abnormal taste, or difficulty in mobility and articulation. No macroglossia was observed in any of these cases. It was thus concluded that DRA of the tongue is a very rare complication, occurring in the late stage of long-term hemodialysis patients, that disturbs their quality of life.

Adult↗
PubMed1997

Mechanism of contraction induced by bradykinin in the rabbit saphenous vein.

1. By using fura-PE3 fluorometry and receptor-coupled permeabilization by alpha-toxin, the mechanism of the bradykinin (BK)-induced contraction was determined in the rabbit saphenous vein (RSV). The receptor subtype responsible for the BK-induced contraction of RSV was determined by means of a pharmacological blocker study and reverse transcription polymerase chain reaction (RT-PCR). 2. In the presence of extracellular Ca2+ (1.25 mM), BK (10(-11)-3 x 10(-7) M) induced increases in both the cytosolic Ca2+ concentration ([Ca2+]i) and force, in a concentration-dependent manner. Both the release of Ca2+ from the store site and the influx of extracellular Ca2+ contribute to an increase in [Ca2+]i induced by BK. 3. In the absence of extracellular Ca2+, the application of 10(-7) M BK induced transient elevations of [Ca2+]i and force, both of which thereafter declined to the levels observed before the application of BK. When extracellular Ca2+ was replenished (1.25 mM), [Ca2+]i and force increased to form a peak, followed by a sustained elevation in the presence of BK. When an RSV strip was pretreated with 10(-5) M thapsigargin for 20 min, the BK-induced transient increases in both [Ca2+]i and force were markedly inhibited. 4. These responses induced by BK were inhibited by Hoe 140 (D-Arg-[Hyp3, Thi5, D-Tic7, Oic8] bradykinin), a highly specific bradykinin B2 receptor antagonist, in a concentration-dependent manner. In RT-PCR, B2-receptor mRNA was expressed in the smooth muscle of RSV. 5. The [Ca2+]i-force relationships, which were determined by cumulative applications of extracellular Ca2+ (0-5 mM) during 118 mM K(+)-depolarization, shifted to the upper left in the presence of BK, thus indicating that BK induced a greater force than 118 mM K(+)-depolarization for a given level of [Ca2+]i. 6. In alpha-toxin-permeabilized preparations of RSV, application of 10(-7) M BK after a steady state contraction had been induced by a mixture of 5 x 10(-7) M Ca2+, 10(-6) M GTP and 10(-6) M captopril caused an additional force development at a constant [Ca2+]i. However, treatment with 1 mM guanosine-5'-O-(beta-thiodiphosphate) (GDP beta S) for 5 min before and during the application of BK (10(-7) M), abolished this BK-induced additional contraction. 7. These results indicated that in RSV: (1) BK elicits vasoconstriction by increasing the Ca2+ influx from the extracellular space, Ca2+ release from intracellular thapsigargin-sensitive storage sites and increasing the Ca2+ sensitivity of the contractile apparatus, (2) the BK-induced increase in Ca2+ sensitivity is mediated by G-protein, (3) the BK-induced contractions are mediated via B2-receptors and (4) the smooth muscle cells express B2-receptor mRNA.

Animals↗
PubMed1997

HVJ (Sendai virus)-cationic liposomes: a novel and potentially effective liposome-mediated technique for gene transfer to the airway epithelium.

We designed a novel technique for targeted gene transfer into the airway epithelium. This was constructed using multilamellar cationic liposomes, containing N-(alpha-trimethylammonioacetyl)-didodecyl-D-glutamate chloride, phosphatidylcholine and cholesterol and fused with haemagglutinating virus of Japan (HVJ), namely HVJ cationic liposomes. Single aerosol delivery of this novel vector to the airway of rats led to a highly efficient and widespread transduction of fluorescein isothiocyanate-labeled oligonucleotides or lacZ gene into the bronchial epithelium and alveolar macrophages, but not into the alveolar epithelium. The efficiency of gene transfer to the airway epithelium with a single administration of the lacZ gene was about 47.6% in the trachea, 39.0% in the bronchi and proximal bronchioli, and 2.9% in the terminal bronchioli, respectively (mean value, n = 6). Expression level of the luciferase gene delivered with this novel system was much higher than that without HVJ, in both the trachea and lung tissue. Two pretreatment HVJ-cationic liposome vehicles every other week resulted in minimal inflammatory infiltration in the sub-epithelial layer with no significant reduction in efficiency of the following gene transfer. We propose that this novel HVJ cationic liposome-mediated gene transfer system may be suitable for clinical gene therapy to treat subjects with lethal lung diseases such as cystic fibrosis.

Animals↗