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Biomedical subjects

S Fujii

Publications and source records attributed to S Fujii.

At least 451 records · Page 25Linked to original sources
PubMed1994

Modulation of expression of monocyte/macrophage plasminogen activator activity and its implications for attenuation of vasculopathy.

BACKGROUND: The binding of urokinase-type plasminogen activator (uPA) to its receptor (uPAR) on cell surfaces has the potential to influence degradation of extracellular matrix (ECM). Thus, uPA bound to monocyte/macrophages and its interactions with plasminogen activator inhibitors types 1 and 2 (PAI-1 and PAI-2) may modify atherogenesis by altering cell-associated proteolytic activity, degradation of ECM, and neointimal formation at sites of vascular injury. METHODS AND RESULTS: To determine whether the expression of proteins on the surface of cells involved in fibrinolysis changes in human cells in response to mediators implicated in atherogenesis, we exposed U937 cells (an immortal human monocyte-like cell line) to transforming growth factor-beta (TGF-beta) and to thrombin. Induction of uPAR mRNA occurred with TGF-beta (5 ng/mL) in a time-dependent fashion (P = .05; n = 4). Thrombin (5 National Institutes of Health [NIH] U/mL) increased uPAR mRNA by 2.8-fold above control (n = 4) without altering PAI-1 mRNA or protein synthesis (n = 4). The increase in uPAR gene expression in cells exposed to either TGF-beta or thrombin translated into a functional increase in cell-surface proteolytic activity. Under control conditions, U937 cells expressed PAI-2 but not PAI-1 mRNA. PAI-2 mRNA expression increased (P < .05; n = 4) with thrombin (5 NIH U/mL) but was suppressed by TGF-beta (5 ng/mL). TGF-beta induced PAI-1 mRNA within 6 hours accompanied by a 9-fold increase in PAI-1 protein from 6 hours (2.9 +/- 1.9 ng/mL) to 24 hours (20.0 +/- 9.6 ng/mL, P = .005; n = 3) paralleled by increased synthesis as shown in metabolic labeling experiments with 35S-methionine and immunoprecipitation of labeled PAI-1. PAI-1 mRNA and protein expression were seen in human coronary artery atherectomy specimens as well and were localized to analogous monocyte/macrophages and to smooth muscle cells as judged from results of in situ hybridization and immunocytochemistry studies. CONCLUSIONS: The results indicate that there is induction of PAI-1 and uPAR in U937 cells exposed to TGF-beta and thrombin. In atheroma, analogous processes may modulate early migration of luminal monocytes into the subintimal space and proteolysis of ECM. Thus, cell surface, monocyte-directed fibrinolysis may influence atherosclerosis, restenosis, or both.

Cell Line↗
PubMed1994

A multi-centre study of the efficacy and safety of pravastatin in hypercholesterolaemic patients with non-insulin-dependent diabetes mellitus.

A multi-centre, non-randomized clinical study of 12-months' duration was performed in 112 patients with hyperlipidaemia associated with non-insulin-dependent diabetes mellitus to evaluate the clinical efficacy and tolerability of pravastatin and to assess its effect on glycaemic control. Patients were eligible for this trial if they fulfilled the following criteria; a high plasma total cholesterol level greater than 220 mg/dl associated with stable glycaemic control for at least 3-months' observation period. On entry, patients received 10 mg pravastatin per day (5 mg twice daily) for 12 months. Clinical efficacy was evaluated in 108 patients. The results showed that pravastatin induced a significant decrease in serum cholesterol level mainly with LDL-cholesterol. Total cholesterol levels were decreased significantly from 275 +/- 3 mg/dl to 222 +/- 4 mg/dl within 3 months of the start of treatment, and LDL-cholesterol decreased from 192 +/- 4 mg/dl to 137 +/- 4 mg/dl. After 12 months' treatment, total cholesterol and LDL-cholesterol levels were 216 +/- 4 mg/dl (p < 0.001) and 137 +/- 5 mg/dl (p < 0.001), respectively. HDL-cholesterol levels were increased from 51 +/- 2 mg/dl to 56 +/- 2 mg/dl at 3 months (p < 0.001) and 55 +/- 2 mg/dl at 12 months (p < 0.01). Triglyceride concentrations were also decreased from 173 +/- 11 mg/dl to 156 +/- 13 mg/dl at 3 months and 137 +/- 10 mg/dl at 12 months (p < 0.01). Fasting plasma glucose and glycated haemoglobin levels were not affected by pravastatin. Adverse events observed in 5 cases were always mild and reversible. These results indicate a clinical usefulness of pravastatin with high compliance in patients with hyperlipidaemia associated with non-insulin-dependent diabetes mellitus.

Adult↗
PubMed1994

Distribution of substance P-containing and catecholaminergic nerve fibers in the rabbit carotid body: an immunohistochemical study in combination with catecholamine fluorescent histochemistry.

The distribution of substance P (SP)-immunoreactive nerve fibers in the rabbit carotid body was studied in combination with catecholamine autofluorescence images of sections where SP immunoreactivity was confirmed. Immunoreactivity for SP was found in nerve fibers distributed in the parenchyma of the carotid body. No glomus cells with SP immunoreactivity were observed in the carotid body. On comparing the distribution of SP-immunoreactive fibers with the catecholamine autofluorescence image in a single section, most SP fibers appeared associated with the fluorescent glomus cells, and were located around clusters of them. These results support the suggestion that SP fibers in the cat and rat carotid bodies are involved in chemosensory mechanisms. Furthermore, a survey of the present results and previous ones reported by other workers indicates that SP may be an essential neuropeptide in chemoreceptor organs in most vertebrates from amphibians on upwards evolutionally. In addition, the courses of some catecholaminergic fibers precisely agreed with those of some SP fibers. This suggests that certain sympathetic nerve fibers also contain SP.

Animals↗
PubMed1994

Complementary improvement of the method for determining cholinergic activities in the small intestine and its application to experiments in vivo.

The concentration of acetylcholine (ACh) in rat jejunum that had been homogenized with an ultra-high-speed homogenizer (Biotron) was significantly higher than that in jejunum homogenized with a glass homogenizer. Rats were injected once or repeatedly for 10 days with a muscarinic agonist, pilocarpine (1 mg/kg), or a muscarinic antagonist, scopolamine (5 mg/kg). Animals were killed 20 min or 24 hr after single or consecutive injections, respectively, for determinations of cholinergic activities in the jejunum. Single treatment: Pilocarpine did not cause significant changes in the level of ACh, the activity of acetylcholinesterase (AChE), the binding of [3H]quinuclidinyl benzilate (QNB) or the contractile responses to ACh. Scopolamine reduced the level of ACh and binding of [3H]QNB without inducing significant changes in the activity of AChE and the contractile response. Consecutive treatment: Pilocarpine reduced the binding of [3H]QNB by changing the value of Bmax and reduced the contractile response without affecting the level of ACh or the activity of AChE. Scopolamine increased the binding of [3H]QNB without any effects on the level of ACh, the activity of AChE or the contractile response. In summary, it is possible to determine the level of ACh in a tissue as hard as intestine by homogenization with a Biotron and to assess the cholinergic situation in the intestine of animals that have been poisoned with various agents by estimating cholinergic activities.

Acetylcholine↗
PubMed1994

Wrap-clipping with a Dacron mesh silastic sheet. Technical note.

A technique combining wrapping and clipping using a Silastic sheet coated with Dacron mesh is described for treatment of fusiform or broad-based cerebral aneurysms. This sheet is easily tailored to wrapping the aneurysm base while avoiding involvement of the cranial nerves or branching vessels. The sheet is semitransparent so that the caliber of the newly constructed parent artery is easily adjusted during wrap-clipping. After the aneurysm and the parent artery have been circumferentially wrapped with the sheet, aneurysm clips are applied on the sheet so that the base of the aneurysm is clipped between the two leaves of the sheet. This wrap-clipping technique avoids the risks involved in extracting the aneurysm from the parent artery. The Dacron mesh coating the outer surface and sufficient clip closing pressure are both helpful in preventing the clip blades from sliding. Similar previously reported techniques are reviewed and discussed in detail.

Humans↗
PubMed1994

[A case report of coronary artery bypass grafting surgery with aprotinin in a patient undergoing chronic haemodialysis].

A 61-year-old patient who was receiving haemodialysis because of chronic renal failure developed unstable angina pectoris with three vessel disease. We performed successful coronary artery bypass grafting, using aprotinin to reduce blood loss. Blood loss during the operation was 750 ml, and during a 6 hour period after the operation it was 150 ml. This amount seemed to be small. No adverse clinical effects attributable to aprotinin were seen, and urine volume and plasma creatinine were not different before and after the operation. In summary, aprotinin is useful adjunct to open heart surgery in chronic haemodialysis patients.

Aprotinin↗
PubMed1994

[Quantitative hemodynamic assessment of internal thoracic artery grafts using transthoracic duplex imaging].

The hemodynamics of blood flow in internal thoracic artery (ITA) grafts were studied using transthoracic duplex imaging prior to and following coronary artery bypass grafting (CABG) in 37 patients. Transthoracic images of the ITA were obtained through the first intercostal space using a 7.5 MHz probe, and their diameter and area were measured by B-mode imaging. Systolic, diastolic, mean and end-diastolic blood flow velocity (Vs, Vd, Vm, and Ved) were determined based on Doppler signals and systolic, diastolic, and total blood flow (Fs, Fd, and Ftotal) were calculated by the following formula: Flow = Vm x area x 60/10(3). The diameter of the ITA increased following CABG. Prior to CABG, Vs, and Fs, were dominant, while following CABG, the hemodynamic pattern was diastolic dominant, although individual variation existed. The ITA blood flow was measured in 4 groups, in patients who had had a previous anterior myocardial infarction and no redistribution on myocardial scintigraphy (group I), in patients with 99-100% coronary artery stenosis who had not had an anterior myocardial infarction or who had an anterior myocardial infarction and had redistribution (group IIa), in patients with the same criteria as group IIa but who had 90% coronary stenosis (group IIb), and in patients with 75% coronary stenosis who had not had anterior myocardial infarction (group IIc). Blood flow was 57, 73, 44mL and 34 mL/min, and the percentage of diastolic flow was 72, 69, 61, 59% respectively. These results show that ITA blood flow competes with native coronary artery flow in patients with moderate coronary stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Successful treatment of refractory extensive small cell lung cancer by oral etoposide].

A 62-year-old male was admitted with chest pain and lymphadenopathy at neck for 2 weeks. His admission chest radiograph revealed a large tumor shadow, intrapulmonary metastasis and apical involvement. The patient was diagnosed as having small cell lung cancer from sputum cytology. Clinical staging was extensive disease and performance status was 1. The patient was treated by combination chemotherapy with cisplatin, adriamycin and etoposide. After 4 cycles, his chest radiograph was unchanged and he showed remarkable bone marrow suppression and superior vena cava syndrome. Thus, the initial combination chemotherapy was thought to be ineffective. Then, administration of oral etoposide (50 mg/body) was started and continued until the appearance of leukopenia (< 3,000/mm3). One month's administration of oral etoposide made the tumor shadow on his chest radiograph disappear. This disappearance was reserved for more than 4 months with oral etoposide. The average administration of oral etoposide was 2.7 day/week.

Administration, Oral↗
PubMed1994

[Clinical significance of endocervical curettage (ECC) in predicting neoplastic lesions of the cervix].

Endocervical curettage (ECC) was routinely performed at the time of colposcopy on 200 cases with an abnormal PAP smear. Colposcopically, 77 cases were normal, 99 were abnormal, and 24 were unsatisfactory. Results of the directed biopsies were within normal limits for 84 cases, glandular dysplasia for 2, squamous dysplasia for 95, carcinoma in situ (CIS) for 17, and squamous cell carcinoma for 3. Histologic diagnoses of the ECC specimens were "tissue insufficient for diagnosis" for 11 cases, "benign endocervical tissue" for 167 including 9 squamous metaplasias and 3 cervical polyps, "fragments of dysplasia" for 12, CIS for 6, and squamous carcinoma for 4. Regarding 73 cases who underwent surgical treatment, the biopsy diagnosis had been either false negative in 6 cases or underestimated in 5 cases as compared to the confirmed diagnosis. That is to say, 11 cases might have been diagnosed incorrectly without ECC. The major lesion was located within the endocervix in most of such cases. It is therefore suggested that ECC improves the accuracy of the histologic diagnosis of premalignant and malignant lesions of the cervix and that ECC is an essential procedure especially in endocervical lesions.

Adenoma↗
PubMed1993

Regulation of renal cytochrome P450s by thyroid hormone in diabetic rats.

Effects of thyroid hormone treatment on renal P450 expression in the diabetic rats were investigated. Diabetes produced by streptozotocin induced CYP4A2 and P450 K-2 (similar form with CYP2C23) but not P450 K-4 (similar form with CYP4A8) and induced lauric acid hydroxylation activity. The serum thyroid hormone level was decreased with diabetes. Treatment of diabetic rats with thyroid hormone (T3) as well as with insulin reversed the increase in the levels of CYP4A2 and P450 K-2. Thyroidectomy also induced CYP4A2 and P450 K-2 in the rat kidney. The increase was reversed by treatment of thyroidectomized rats with T3. These findings suggest that expression of CYP4A2 and P450 K-2 in rat kidney is suppressively regulated by thyroid hormone and the decrease in thyroid hormone level in the diabetic state affects the levels of CYP4A2 and P450 K-2.

Animals↗
PubMed1993

NMR studies of G:A mismatches in oligodeoxyribonucleotide duplexes modelled after ribozymes.

The structures of two oligodeoxyribonucleotide duplexes, the base sequences of which were modelled after both a hammerhead ribozyme and a small metalloribozyme, were studied by NMR. Both duplexes contain adjacent G:A mismatches; one has a PyGAPu:PyGAPu sequence and the other a PyGAPy:PuGAPu sequence. It is concluded on the basis of many characteristic NOEs that in both duplexes G:A base pairs are formed in the unique 'sheared' form, where an amino proton instead of an imino proton of G is involved in the hydrogen bonding, and G and A bases are arranged 'side by side' instead of 'head to head'. A photo-CIDNP experiment, which gives unique and independent information on the solvent accessibility of nucleotide bases, also supports G:A base pairing rather than a bulged-out structure of G and A residues. This is the first demonstration that not only the PyGAPu:PyGAPu sequence but also the PyGAPy:PuGAPu sequence can form the unique sheared G:A base pairs. Taking the previous studies on G:A mismatches into account, the idea is suggested that a PyGA:GAPu sequence is a minimum and essential element for the formation of the sheared G:A base pairs. The sheared G:A base pairs in the PyGAPu:PyGAPu sequence are suggested to be more stable than those in the PyGAPy:PuGAPu sequence. This is explained rationally by the idea proposed above.

Base Sequence↗
PubMed1993

Expression of c-erbB-2 protein and epidermal growth receptor in endometrial carcinomas. Correlation with clinicopathologic and sex steroid receptor status.

BACKGROUND: The c-erbB-2 (HER-2/neu) protein is a membrane glycoprotein growth factor receptor showing molecular homology with the epidermal growth factor receptor (EGFR). In endometrial carcinomas, little is known about the relationship between the expression of c-erbB-2 protein and that of EGFR. METHODS: The immunohistochemical reactivity of monoclonal antibodies against both of these proteins was examined in 34 endometrial carcinomas, and the presence or absence of correlation with the clinicopathologic features or with the immunohistochemical expression of sex steroid receptors (estrogen receptor [ER] and progesterone receptor [PR]) was analyzed. RESULTS: Of the 34 patients, 22 (64.7%) had c-erbB-2 protein-positive and EGFR-negative tumor, and 8 (23.5%) had tumor positivity for both proteins. Four patients had tumors negative for both proteins. ER or PR positivity was found in 24 (70.6%) of the 34 patients. Intense immunostaining for c-erbB-2 protein was found in 5 (14.7%) of the 34 patients but was not correlated with the stage or grade of differentiation in endometrial carcinoma. However, expression of EGFR in addition to c-erbB-2 protein was more frequently observed with advancing stage of disease and was inversely correlated with the grade of differentiation and with the expression of ER or PR of the tumor. CONCLUSION: The expression of EGFR, in addition to that of c-erbB-2 protein, is an important event that presumably is linked with progression or with a poorly differentiated state of endometrial carcinomas.

Adult↗
PubMed1993

Inhibition of endothelial cell expression of plasminogen activator inhibitor type-1 by gemfibrozil.

Increased concentrations of plasminogen activator inhibitor type-1 (PAI-1) in plasma are associated with impaired fibrinolysis and venous and arterial thrombo-embolic disease. In pilot studies designed to identify pharmacologic approaches capable of diminishing such increases, we found that gemfibrozil attenuated the stimulation of synthesis of PAI-1 in a human, immortal, hepatoma cell line (Hep G2) induced by platelets. The present study was performed to determine whether it exerts analogous effects in non-immortal endothelial cells and whether it may therefore facilitate fibrinolysis locally in vivo. Human umbilical vein endothelial cells were incubated with pharmacologic concentrations of gemfibrozil. Gemfibrozil, 100 microM, suppressed basal PAI-1 production by 15% and attenuated the augmentation of synthesis of PAI-1 induced by lysates from platelets (4 x 10(7)/ml) by 36% over 24 h without inhibiting overall protein synthesis. In addition, the increases in PAI-1 mRNA otherwise induced by platelet lysates over 6 h were suppressed by 49% (Northern blots) without any demonstrable change in the intracellular half-life of PAI-1 mRNA. Pulse-chase experiments demonstrated diminution of PAI-1 protein synthesis in parallel with the changes observed in PAI-1 mRNA. To determine whether these effects of gemfibrozil on endothelial cells in vitro were paralleled by consistent changes in the concentrations of PAI-1 in plasma in vivo, we studied rabbits with induced carotid artery thrombosis and thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Changes in amounts of cytochrome P450 isozymes and levels of catalytic activities in hepatic and renal microsomes of rats with streptozocin-induced diabetes.

Hepatic microsomal cytochrome P450s, which are involved in the metabolism of drugs, hormones, prostaglandins and fatty acids, change when animals develop diabetes. We studied changes in cytochrome P450 isozymes in both hepatic and renal microsomes of rats with diabetes caused by streptozocin, and compared the results with changes in catalytic activities in the microsomes. In hepatic microsomes of diabetic rats, the amount of cytochrome P450 2E1, an acetone-inducible isozyme, was two and a half times that of control rats, and that of P450 4A2, a major renal isozyme, was three times that in the controls. The amounts of cytochrome P450s 2A1, 2C6, 2C7, 3A2 and 4A3 increased in hepatic microsomes of diabetic rats, and P450 2C11 decreased. Treatment with insulin restored these to the levels in the controls. The catalytic activities of aniline hydroxylation, 7-ethoxycoumarin O-dealkylation, testosterone 2 beta, 6 beta, 7 alpha, and 16 beta-hydroxylation, and omega-, (omega-1)-hydroxylation of lauric acid were high in the hepatic microsomes of diabetic rats, and testosterone 2 alpha and 16 alpha-hydroxylation activities were low. In renal microsomes of diabetic rats, cytochrome P450s 2E1, 4A2 and K-4 were induced, and omega- and (omega-1)-hydroxylation activities were high. These changes were reversed by insulin treatment. The induction and suppression of cytochrome P450 isozymes in diabetic rats were consistent with the changes in the catalytic activities. In both hepatic and renal microsomes, P450s 2E1 and 4A2 were induced, altered metabolism of ketones and fatty acids in diabetes may contribute to these changes.

Animals↗
PubMed1993

[The effect of alacepril on insulin sensitivity in patients with essential hypertension].

The aim of this study was to determine the effect of angiotensin-converting-enzyme inhibitor, alacepril, on insulin sensitivity in patients with essential hypertension (EHT). Ten patients (5 men and 5 women) with EHT (3 with mild diabetes and 2 with borderline glucose tolerance) participated. We measured insulin sensitivity using the two-hour euglycemic-hyperinsulinemic clamp technique and plasma glucose and insulin responses to a 75 g oral glucose tolerance test (75 g OGTT) before and after 6-8 weeks of treatment with alacepril (dose, 50 mg/day). Glucose infusion rate (GIR) during the last 30 min of the clamp study increased from 5.83 +/- 0.70 to 6.59 +/- 0.65 mg per kilogram of body weight per minute (P < 0.05) after treatment with alacepril. The insulin-sensitivity index, which was calculated by dividing the GIR by the mean insulin concentration during the same period of the clamp, also increased from 5.91 +/- 0.66 to 7.20 +/- 0.90 (P < 0.05) after treatment with alacepril. Plasma glucose responses to a 75 g OGTT were changed from diabetic pattern to borderline pattern in two patients and from borderline pattern to normal pattern in one patient after treatment with alacepril. Body weight did not significantly change throughout the study in any of the patients studied. Our study demonstrated that alacepril significantly improves insulin sensitivity in patients with EHT.

Adult↗
PubMed1993

Hydrostatic pressure is like high temperature and oxidative stress in the damage it causes to yeast.

A comparison of barotolerance, thermotolerance and oxygen tolerance was made under different physiological conditions, such as heat shocked and recovered state, different growth phases and changes of physiological conditions by mutations. The three kinds of tolerance showed similar features under different physiological conditions. We suggest that the damage caused by hydrostatic pressure may be essentially the same as that due to high temperature and oxidative stress in yeast.

Hot Temperature↗
PubMed1993

Coexistence of substance P and calcitonin gene-related peptide in the nerve fibers of the carotid labyrinth of the bullfrog, Rana catesbeiana.

Double immunohistochemical staining with fluorescein isothiocyanate (FITC)- and rhodamine-conjugated antisera revealed the coexistence of substance P (SP) and calcitonin gene-related peptide (CGRP) in most nerve fibers in the intervascular stroma of the carotid labyrinth of the bullfrog, Rana catesbeiana. A few fibers contained SP without CGRP. The results suggest that the vascular regulatory function, which is one of the possible functions of the carotid labyrinth, may be controlled in part by the interaction of SP and CGRP.

Animals↗