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Percutaneous drainage and continuous irrigation in patients with severe pyogenic spondylitis, abscess formation, and marked bone destruction.

OBJECT: The use of percutaneous suction aspiration has recently become viewed as an effective management strategy for pyogenic spondylitis unresponsive to conservative treatment. What remains unclear is whether it can be effective for severe pyogenic spondylitis in which abscess formation or marked bone destruction is present. The authors undertook a study to clarify answers to this question. METHODS: The authors evaluated clinical and radiographic/neuroimaging data obtained in five patients with severe pyogenic spondylitis, extensive abscesses, and marked bone destruction. These patients had undergone percutaneous drainage and continuous irrigation because open surgery was considered contraindicated in light of their poor general health. The mean period during which continuous irrigation was applied was 9 days (range 7-11 days), and the mean period during which the drainage tube was in place was 19 days (range 13-38 days). All patients suffered from back pain, which was relieved by the percutaneous technique in four patients after a mean of 8 days. The abscesses and inflammation resolved in all patients. Progressive osseous destruction was not observed, and open surgery was performed in only one patient in whom back pain persisted as a result of spinal instability. CONCLUSIONS: After an unsuccessful course of conservative treatment, severe pyogenic spondylitis with abscess formation or marked bone destruction was successfully treated using percutaneous drainage and continuous irrigation. Based on their results, the authors believe that this procedure can be used in patients with severe pyogenic spondylitis that was unresponsive to conservative treatment, particularly in those whose general health is poor.

Aged↗

Total parathyroidectomy reduces elevated circulating fibroblast growth factor 23 in advanced secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism is a common complication in patients with stage 5 chronic kidney disease (CKD), accelerated by hyperphosphatemia. Fibroblast growth factor 23 (FGF-23), a phosphorus-regulating protein, has key roles in several phosphate-wasting disorders. The aim of this study is to examine the association of advanced secondary hyperparathyroidism with circulating FGF-23 levels. METHODS: Fifteen patients with marked secondary hyperparathyroidism (parathyroid hormone [PTH], 990 +/- 118 pg/mL [ng/L]) were enrolled. All underwent parathyroidectomy with forearm autotransplantation (PTX), and their FGF-23 levels were measured before and after PTX (days 1, 3, 7, and 10) by means of sandwich enzyme-linked immunosorbent assay. RESULTS: Preoperative FGF-23 levels correlated positively with phosphorus (P < 0.05), calcium-phosphorus product (Ca x P; P < 0.0005), and PTH values (P < 0.05). Serum FGF-23 levels decreased time dependently after PTX (P < 0.0005). Both serum phosphorus and Ca x P values decreased similarly after PTX ( P = 0.0001). Furthermore, FGF-23 levels days 1 and 3 correlated linearly with serum phosphorus (P < 0.05; P < 0.005, respectively) and Ca x P values (P < 0.01; P < 0.0001, respectively). CONCLUSION: FGF-23 levels correlate positively with serum phosphorus, Ca x P, and PTH values in patients with advanced secondary hyperparathyroidism. Complete ablation of progressive parathyroid glands reduces circulating FGF-23 levels, simultaneously decreasing serum phosphorus and Ca x P values. These findings suggest that hyperplastic parathyroid glands, together with hyperphosphatemia, affect abnormal FGF-23 metabolism in patients with stage 5 CKD with advanced secondary hyperparathyroidism.

Chronic Disease↗

Cytokine regulation of gut ornithine decarboxylase gene expression and enzyme activity.

BACKGROUND: The enzyme ornithine decarboxylase (ODC) catalyzes the rate-limiting step in polyamine biosynthesis and is important for gut mucosal repair after systemic injury (e.g., burns); however, the mechanisms responsible for the injury-mediated induction of ODC are not known. The purpose of this study was to determine whether interleukin-1 (IL-1) or tumor necrosis factor (TNF), which are released immediately after injury, regulates gut mucosal ODC enzyme activity and gene expression. METHODS: In vivo: In experiment 1, 64 male BALB/c mice received either recombinant IL-1 beta (2 x 10(4) units/kg administered intraperitoneally) or saline solution. In experiment 2, 64 mice received either recombinant TNF-alpha (100 micrograms/kg administered intraperitoneally) or saline solution. We determined ODC enzyme activity and ODC mRNA levels in small intestine and kidneys at 2, 4, 12, and 24 hours after injection. In vitro: We also determined the ODC enzyme activity in intestinal epithelial crypt cells after either IL-1 beta or TNF-alpha treatment. RESULTS: IL-1, but not TNF, increased small intestinal ODC enzyme activity. In addition, IL-1 increased ODC enzyme activity in intestinal epithelial crypt cells at 5 and 6 hours after treatment. Both IL-1 and TNF increased small intestinal ODC mRNA levels. Neither agent affected ODC enzyme activity or ODC mRNA levels in the kidney. CONCLUSIONS: These results suggest that the cytokine-mediated induction of ODC in the small intestine is tissue specific, that the induction occurs at multiple cellular levels, and that ODC may play a vital role in the restoration of gut mucosa that occurs after injury.

Animals↗

Sodium sensitivity and sympathetic nervous system in hypertension induced by long-term nitric oxide blockade in rats.

1. Pharmacological inhibition of nitric oxide (NO) synthesis is known to produce acute and chronic hypertension in many animal species, but the underlying mechanisms mediating the hypertension are not completely understood. In particular, the pathogenetic roles of sodium sensitivity and the sympathetic nervous system in this model of hypertension are controversial. The present study was designed to test the hypothesis that long-term administration of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) to male Sprague-Dawley rats would produce a sodium-sensitive hypertension and that the enhanced activity of the sympathetic nervous system in this type of hypertension contributes to the sodium sensitivity. 2. NG-Nitro-L-arginine methyl ester was added to drinking fluid for 8 weeks at a concentration of 16 mg/dL. Rats received tap water for the first 4 weeks of the study and were then divided into two groups and placed on either a normal or high sodium intake (ingestion of either tap water or 0.9% NaCl, respectively). Awake systolic blood pressure was measured by the tail-cuff method every week. Urinary excretion rates of the stable NO metabolites and catecholamines during NO synthesis inhibition were examined. 3. Long-term administration of L-NAME produced a marked and sustained elevation in arterial pressure without altering urine flow, or sodium excretion rate. NG-Nitro-L-arginine methyl ester-induced hypertension was accompanied by a decreased urinary excretion of the stable NO metabolites NO2- and NO3- and was aggravated when rats drank 0.9% NaCl in place of tap water. Urinary excretion of adrenaline and noradrenaline, but not dopamine, in L-NAME-treated rats increased significantly within the first week of the study compared with control rats. L-Arginine (2 g/dL in drinking fluid) completely reversed the elevation of arterial pressure as well as the decrease in urinary NO2- and NO3- excretion and the increased urinary excretion of catecholamines associated with L-NAME treatment by 3 weeks of concomitant administration. 4. These results suggest that long-term inhibition of NO synthesis produces a sodium-sensitive hypertension and that changes in sympathetic nerve activity may, at least in part, contribute to the sodium sensitivity in this type of hypertension.

Animals↗

Volume turnover kinetics of fluid shifts after hemorrhage, fluid infusion, and the combination of hemorrhage and fluid infusion in sheep.

BACKGROUND: Hemorrhage is commonly treated with intravenous infusion of crystalloids. However, the dynamics of fluid shifts between body fluid spaces are not completely known, causing contradictory recommendations regarding timing and volume of fluid infusions. The authors have developed a turnover model that characterizes these fluid shifts. METHODS: Conscious, chronically instrumented sheep (n = 12) were randomly assigned to three protocol groups: infusion of 25 ml/kg of 0.9% saline over 20 min (infusion only), hemorrhage of 300 ml (7.8 +/- 1.1 ml/kg) over 5 min (hemorrhage only), and hemorrhage of 300 ml over 5 min followed by infusion as noted above (hemorrhage plus infusion). A two-compartment volume turnover kinetic model containing seven model parameters was fitted to data obtained by repeated sampling of hemoglobin concentration and urinary excretion. RESULTS: The volume turnover model successfully predicted fluid shifts. Mean baseline volumes of the central and tissue compartments were 1799 +/- 1276 ml and 7653 +/- 5478 ml, respectively. Immediate fluid infusion failed to prevent hemorrhage-induced depression of cardiac output and diuresis. The model suggested that volume recruitment to the central compartment after hemorrhage was primarily achieved by mechanisms other than volume equilibration between the two model compartments. CONCLUSION: Volume turnover kinetics is a promising tool for explaining fluid shifts between body compartments after perturbations such as hemorrhage and intravenous fluid infusions. The pronounced inhibition of renal output after hemorrhage prevailed regardless of fluid infusion and caused fluid retention, which expanded the tissue compartment.

Algorithms↗

Pancreatitis: evaluation with MR cholangiopancreatography in children.

PURPOSE: To determine the usefulness of magnetic resonance (MR) cholangiopancreatography in assessing the cause of pancreatitis in children. MATERIALS AND METHODS: Twenty healthy volunteers (aged 2-11 years) and 10 patients with acute pancreatitis (aged 3-12 years) who underwent MR cholangiopancreatography between December 1993 and February 1996 were studied retrospectively. The rate of visualization of the common bile duct and main pancreatic duct with MR cholangiopancreatography was assessed in the volunteer group. Depiction of pancreaticobiliary disease at MR cholangiopancreatography was assessed in the patient group. RESULTS: MR cholangiopancreatography clearly showed the common bile duct in 20 of 20 volunteers (100%) and the main pancreatic duct in 13 of 20 volunteers (65%). MR cholangiopancreatography depicted a dilated common bile duct in six of 10 patients (60%) and an abnormal arrangement of the pancreaticobiliary duct in five of the six patients (83%) in whom this structural abnormality was proved at surgery. In the four patients without structural abnormality, MR cholangiopancreatography depicted a pseudocyst in one patient who had traumatic pancreatitis; the other three patients had normal findings. In one of these three patients, familial pancreatitis was considered to be the underlying disorder, and in the other two patients no cause was identified. CONCLUSION: MR cholangiopancreatography may be helpful in diagnosing the cause of pancreatitis in children, especially in those with an abnormal pancreaticobiliary ductal junction.

Acute Disease↗

[Met-enkephalin-Arg-Gly-Leu-like immunoreactivity-containing nerve elements in the canine pancreas--an immunohistochemical study].

The occurrence and localization of Met-enkephalin-Arg-Gly-Leu (Met-Enk-Arg-Gly-Leu)-like immunoreactivity in the canine pancreas were studied by immunocytochemistry. For light microscopy, Bouin fixed and paraffin embedded sections were immunostained by the PAP method. For electron microscopy, ultrathin sections of 4% paraformaldehyde-fixed and Araldite embedded materials were immunostained by a protein A-colloidal gold method. The results obtained were as follows: In light microscopy, Met-Enk-Arg-Gly-Leu-like immunoreactivity was localized in nerve fibers of autonomic ganglion, in beaded nerve terminals around blood vessels of the exocrine parenchyma and pancreatic islet, in eighty-five out of one hundred and seventy-four ganglion cell somas of intra- and interlobular ganglia, and in ganglion cell somas and nerve fibers of neuro-insular complexes. In electron microscopy, colloidal gold particles representing Met-Enk-Arg-Gly-Leu-like immunoreactivity were concentrated on secretory type granules of the ganglion cell somas and on large cored synaptic vesicles of the nerve terminals around blood capillaries. All the positive immunoreactions disappeared with preincubation of the anti-Met-Enk-Arg-Gly-Leu serum (dilution, 1:4,000) with Met-Enk-Arg-Gly-Leu (10 micrograms/ml). Immunostaining was not affected by preincubation of the antiserum with Met-enkephalin (10 micrograms/ml), Leu-enkephalin (10 micrograms/ml) and Met-enkephalin-Arg-Phe (20 micrograms/ml). Out of the three precursors for a variety of opioid peptides throughout the body, i.e. preproenkephalin A, preproopiomelanocortin and preproenkephalin B, only preproenkephalin A contains Met-Enk-Arg-Gly-Leu.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Effects of nitrendipine on circadian variation of blood pressure in inpatients with renal parenchymal hypertension: assessment by ambulatory blood pressure monitoring].

OBJECTIVE: To study the effect of once-daily administration of a nitrendipine tablet 10 mg on 24-hour ambulatory blood pressure in inpatients with renal parenchymal hypertension. METHODS: Sixteen patients participated in the present study, and one patient was withdrawn because the baseline office blood pressure was less than 140/90 mmHg. In the baseline period, ambulatory blood pressure was monitored every 30 minutes for 30 hours. After the baseline measurement, nitrendipine 10 mg was orally administered once daily every morning for 7 days. The 30-hour ambulatory blood pressure monitoring was repeated after Day 6. RESULTS: Fifteen patients (aged 64.9 +/- 15.0 years) completed the study protocol. Baseline office blood pressure was 157.9 +/- 17.5/84.7 +/- 12.5 mmHg (mean +/- SD). Nitrendipine 10 mg tablets significantly reduced both systolic blood pressure (SBP) and diastolic blood pressure (DBP) at least for 11 hours after administration compared with those at baseline. The rate of "Decrease" (reduction in blood pressure > or = 20/10 mmHg and/or achieved blood pressure < 140/90 mmHg at trough point) was 60.0% (9/15). Eleven patients were considered as effective cases at peak point (maximal reduction in blood pressure > or = 20/10 mmHg). The rate of "Decrease" in effective cases at peak point was 72.7% (8/11). CONCLUSION: These results suggest that a once-daily administration of nitrendipine 10 mg tablets is effective for the 24-hour control of blood pressure in patients with renal parenchymal hypertension.

Administration, Oral↗

Localization and properties of NAD+-dependent 15-hydroxyprostaglandin dehydrogenase activity in the rat kidney.

Localization of NAD+-dependent (type I) 15-hydroxyprostaglandin dehydrogenase (15PGDH) in the rat kidney was examined using an ultramicro assay of the enzyme activity based on the enzymatic cycling method. The enzyme activities during first 3 weeks of age were 30- to 40-fold higher than the adult and rapidly decreased by 4th week. 15PGDH activities measured with either PGE2 or PGF2 alpha as a substrate were five times higher in slices from midcortical or juxtamedullary layers than in slices from the superficial cortex of 3 week-old rat kidney. Little activity was found in inner medulla and papilla. When the enzyme activity was assayed using isolated nephron segments dissected from collagenase treated slices of 3 week-old rat kidneys, the activity was localized only in the proximal convoluted and straight tubules with either PGs (PGE2: 1.75 +/- 0.25 in PCT, 7.70 +/- 1.19 in PST, and PGF2 alpha: 1.63 +/- 0.39, 6.18 +/- 1.52 pmoles NADH/mm/40 min). The kinetic analysis for renal 15PGDH of 3 week-old rats revealed that Km for PGE2 (8.4 microM) was lower than that for PGF2 alpha (22.6 microM) with constant NAD+, while Vmax for both was similar. In contrast, both Km and Vmax for NAD+ were identical with either PGs. These data suggest that the rate-limiting factor of type I 15PGDH is the concentration of prostaglandins in the kidney rather than the concentration of NAD+.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Increasing peripapillary atrophy is associated with progressive glaucoma.

OBJECTIVE: This study aimed to determine the incidence and degree of progression of peripapillary atrophy in progressive and nonprogressive glaucoma. STUDY DESIGN: A retrospective cohort study. PARTICIPANTS: A total of 75 eyes of 75 patients were examined. MAIN OUTCOME MEASURES: Qualitative assessment of optic disc, peripapillary atrophy,and visual field change was performed by three experienced, masked, independent observers. METHODS: Rim-disc area ratio and peripapillary atrophy-disc area ratio were measured at baseline and follow-up with computer-aided planimetry. RESULTS: Among 75 eyes studied with an average duration of follow-up of 8 years (range, 4-19 years), 33 (44%) showed progressive optic disc damage. Twenty-one (64%) of 33 eyes with progressive disc damage showed peripapillary atrophy progression, and 7 (17%) of 42 eyes without progressive disc damage showed peripapillary atrophy progression; this difference was significant (P < 0.01). In groups with and without peripapillary atrophy, no statistically significant differences were found for mean intraocular pressure, baseline rim-disc area ratio, or baseline peripapillary atrophy-disc area ratio. However, optic disc progression and visual field progression were statistically more frequent in the group with peripapillary atrophy progression (75% and 54%, respectively) than in the group without peripapillary atrophy progression (26% and 11%, respectively) (P < 0.01). There was a statistically significant correlation between measurements of peripapillary atrophy area increase and disc rim loss over time (r = -0.35, P = 0.002). CONCLUSION: Progression of peripapillary atrophy is associated with progressive optic disc damage and progressive visual field loss in glaucoma and may be used as a marker for progressive glaucomatous damage.

Adult↗

YF476 is a new potent and selective gastrin/cholecystokinin-B receptor antagonist in vitro and in vivo.

BACKGROUND: We newly synthesized YF476 ((R)-1-[2,3-dihydro-2-oxo-1-pivaloylmethyl-5-(2'-pyridyl)-1H-1, 4benzodiazepin-3-yl]-3-(3-methylamino-phenyl)urea) as a gastrin/cholecystokinin-B (CCK-B) receptor antagonist. We investigated the pharmacological profile of YF476 in vitro and in vivo. METHODS: We examined the binding properties of YF476 to the rat brain, cloned canine and cloned human gastrin/CCK-B receptors, and the effect of YF476 on secretagogue-induced gastric acid secretion in rats and Heidenhain pouch dogs. RESULTS: YF476 replaced the specific binding of [125I]CCK-8 to the rat brain, cloned canine and cloned human gastrin/CCK-B receptors, with Ki values of 0.068, 0.62 and 0.19 nM, respectively. The affinity of YF476 for rat brain gastrin/CCK-B receptor was 4100-fold higher than that for rat pancreatic CCK-A receptor. In anaesthetized rats, intravenous YF476 inhibited pentagastrin-induced acid secretion with an ED50 value of 0.0086 micromol/kg, but did not affect histamine- and bethanechol-induced acid secretion at a dose of 10 micromol/kg. In Heidenhain pouch dogs, intravenous and oral YF476 inhibited pentagastrin-stimulated gastric acid secretion in a dose-dependent manner with ED50 values of 0.018 and 0.020 micromol/kg, respectively, but did not affect histamine-induced acid secretion. CONCLUSION: These results suggest that YF476 is an extremely potent and highly selective gastrin/CCK-B receptor antagonist, and that the gastrin/CCK-B receptor is not involved in histamine- or bethanechol-induced gastric acid secretion in dogs or rats.

3T3 Cells↗

Changes in viscoelasticity of the myocardium during cardioplegic arrest.

To evaluate the efficacy of myocardial preservation during open heart surgery, we measured the viscoelasticity of the canine myocardium during cardioplegic arrest. A transfer function method was used for the measurement with a monitoring system consisting of a vibrator, a function generator, accerometers and a signal processor. Six mongrel dogs were put on cardiopulmonary bypass and after measurement of control hemodynamics, they were subjected to cardioplegic arrest at myocardial temperatures ranging from 4 to 32 degrees C. Viscoelasticity was measured at every 15 min and the cardioplegic solution was added every 30 min. After two hr of cardioplegic arrest, the myocardium was reperfused and postischemic hemodynamics were measured after 30 min of non-working beating. Satisfactory myocardial function returned in 3 hearts with the myocardial temperatures below 24 degrees C with myocardial viscoelasticity within the control range. Moderately decreased myocardial contractility was noted in a heart kept at temperature of 27 degrees C and its viscoelasticity remained in the control range of 90 min of ischemia and then began to decrease. In 2 hearts kept at temperatures higher than 29 degrees C, severely depressed myocardial contractility was noted, and viscoelasticity decreased transiently at 45 to 60 min and then returned to control levels. These results suggested usefulness of continuous monitoring of the viscoelasticity in early detection of its degenerative alterations due to impaired myocardial preservation during open heart surgery.

Animals↗

Ultrastructural and histochemical studies on the taste buds in some reptiles.

The taste buds in tortoises (Clemmys japonica and Geoclemys reevesii), lizards (Takydromus tachydromoides) and snakes (Elaphe quadrivirgata) were examined by both ultrastructural and histochemical methods. The taste buds consisted of at least three types of cells: the type I, II and III cells. The type I cells were characterized by the presence of secretory dense granules containing polysaccharides which were demonstrated by periodic acid-chromic acid-silver methenamine technique. The type II cells contained numerous tubular, vesicular and lamellated structures. The type III cells were characterized by dense cored vesicles and afferent synaptic contacts. Besides these cells, basally located cells which resembled the basal cells of other lower vertebrates were sometimes found in the tortoises. After administration of L-DOPA following nialamide, some taste bud cells of the tortoises, Clemmys japonica, showed weak yellowish green fluorescence by monoamine fluorescence histochemistry and the dense-cored vesicles in the type III cells increased in number. Acetylcholine esterase activity was not observed in tortoise taste buds. It is suggested that the three types of cells which compose the taste buds of the reptiles may correspond to the three types of cells in mammalian, and the type III cells represent the gustatory cells which are able to potentially produce biogenic monoamines. From these results, the taste buds of the reptiles may hold an intermediate position between those of mammals and amphibia or fishes.

5-Hydroxytryptophan↗

Analysis of lupus activity in end-stage renal disease treated by hemodialysis.

OBJECTIVE: The activity of systemic lupus erythematosus (SLE) has been reported to decrease in patients who have developed end-stage renal disease (ESRD). However, extrarenal symptoms attributable to the disease activity are noted, especially during the first year of dialysis. We studied the clinical course and evaluate the disease activity of SLE in patients with ESRD on hemodialysis for more than 6 months. SUBJECT AND METHODS: Fourteen patients with SLE who had been initiated on maintenance dialysis at our center between 1982 and 1999 were examined retrospectively. Their clinical details, organ system manifestations, serologic profiles and immunosuppressive treatment regimens were reviewed. Patients with and without postdialysis flaras of SLE were compared statistically. RESULTS: Five patients exhibited 6 SLE flares under treatment with corticosteroids. Two flares occurred within the first year of the initiation of dialysis, and in 1 patient, aggravation of the disease activity was noted 98 months after the initiation of dialysis. Polyarthritis was noted in 5 cases and fever in 4 cases. The serum complement levels decreased in all 6 cases with relapse of SLE activity. Compared with the other 9 patients who did not exhibit SLE relapse, no significant differences were found in 5 patients who did with respect to the demographic and serologic features at the initiation of dialysis. CONCLUSION: We conclude that the disease activity does not always burn out in patients of SLE who show progression to ESRD. SLE flares can sometimes occur even after one year of the initiation of dialysis. SLE patients on dialysis should be carefully followed up by clinical and serological monitoring, and treated by appropriate immunosuppressive therapy.

Adolescent↗

Antitumor effects of the intravesical instillation of heat killed cells of the Lactobacillus casei strain Shirota on the murine orthotopic bladder tumor MBT-2.

PURPOSE: To characterize the potential of heat killed Lactobacillus casei, Shirota strain (LC9018), as an alternative to bacillus Calmette-Guerin (BCG) for treating patients with bladder cancer we investigated the antitumor effects of intravesical instillation of LC9018 in the MBT-2 orthotopic bladder tumor implantation model in C3H/He mice. MATERIALS AND METHODS: LC9018 or BCG, Tokyo 172 strain, was instilled once daily for 10 days starting on the day after orthotopic implantation of MBT-2. Tumor appearance and mean bladder weight on day 21 after tumor implantation were evaluated. Moreover, we investigated the augmentation of local cellular immunity in bladder mucosa by immunohistochemical staining and reverse transcription polymerase chain reaction. RESULTS: Intravesical LC9018 instillation significantly reduced the rate of tumor appearance in 8 of 38 subjects (p <0.001) and mean tumor growth plus or minus standard deviation with a bladder weight of 37 +/- 49 mg. (p <0.001) compared with tumor appearance in 41 of 58 subjects and mean bladder weight 146 +/- 183 mg. in controls. BCG had no significant antitumor activity in the orthotopic implantation model. Intravesical instillation of LC9018 augmented the local expression of antitumor cytokine messenger RNA (interferon-gamma and tumor necrosis factor-alpha) and induced the infiltration of neutrophils surrounded by macrophages that phagocytosed LC9018 cells at the bladder mucosa. CONCLUSIONS: These results suggest that LC9018 is potentially more potent and safer as a therapeutic agent than BCG for superficial bladder tumors. Furthermore, the antitumor effect of LC9018 is exerted via the augmentation of local cell mediated antitumor immunity.

Administration, Intravesical↗

[Assessment of myocardial viability by resting 201Tl SPECT image].

The aim of this study was to assess whether resting 201Tl scintigraphy is superior in detecting viable myocardium than previous conventional methods. We performed not only stress 201Tl SPECT but also resting 201Tl SPECT within one month in 65 patients with coronary artery disease. Resting 201Tl images were quantitatively compared with 4 hour late images of stress study using a polar map. In stress study, redistribution was recognized on 83% (25/30) of non-MI SEGs with perfusion defect in the stress 201Tl image, and on 39% (18/46) of infarcted SEGs. The agreement of resting 201Tl study with 4 hour late images of stress study was shown on 93% (28/30) of non-MI SEGs and on 52% (24/46) of MI SEGs. The increased uptake of 201Tl in resting study, however, was found on 13 (46%) of 28 MI SEGs showing fixed defects in stress study. In stress delayed image with fixed defect, the %Tl uptake of improved SEGs was higher than that of unchanged SEGs (59 +/- 10% vs 48 +/- 11%; p greater than 0.05). There was no viable myocardium which had %Tl uptake less than 40% at stress delayed image. In conclusion, the resting 201Tl imaging will give an important information as for the myocardial viability showing fixed defects, if more than 40% Tl uptake is observed.

Aged↗

[The estrogen-induced changes of estrogen receptor in seminal vesicle of immature castrated rat].

We have already reported that estrogen treatment given to immature castrated rats caused proliferative changes in both collagen and smooth muscle in the seminal vesicles of immature rats detected by light microscopy. Herein, we studied the estrogen-induced changes in estrogen receptor (ER) in the seminal vesicles of immature castrated rats by means of enzyme immunoassay, an immunohistochemical method and RT-PCR, to clarify the mechanism of estrogen induced proliferation of collagen and smooth muscle. Immature rats (3 weeks old) were castrated and left untreated for 3 weeks and then injected subcutaneously with estradiol-17 beta (E2-17 beta, 5 micrograms/day) for 7 days before they were killed. The nuclear ER content per gland, mg tissue and mg protein in the seminal vesicles of castrated rats increased markedly compared with those of non-treated rats. Castration also enhanced ERmRNA expression. The immunohistochemical analysis demonstrated the obvious tissue distribution by which the nuclear ER positive cells were densely distributed in the periglandular stroma. The nuclear ER contents per gland, mg tissue and mg protein in the seminal vesicles of estrogen-treated castrated rats were greater than those in castrated rats. Estrogen treatment further enhanced ERmRNA expression in the castrated rats. The immunohistochemical studies demonstrated that the nuclear ER positive cells appeared among the glandular epithelial cells, basal cells and the peripheral stromal cells, in addition to the periglandular stromal cells. These findings suggest that ER is related to the estrogen induced proliferation of collagen and smooth muscle in the seminal vesicles of immature castrated rats.

Animals↗

Myocardial injection of CA promoter-based plasmid mediates efficient transgene expression in rat heart.

BACKGROUND: Although naked plasmid injection is the safest and most convenient method for gene delivery, a major limitation of this approach is currently poor transgene expression. The CA promoter (chicken beta-actin promoter with cytomegalovirus, CMV, enhancer) is one of the strongest transcriptional control modules found; however, it is uncertain whether a CA promoter-based vector is efficient enough for naked gene therapy in a cardiovascular context. METHODS: The beta-galactosidase (LacZ) expression provided by CA promoter plasmid (pCAZ2) injection into the skeletal muscle or the heart of Lewis rats was compared with CMV promoter plasmid or adenoviral vector (AxCAZ3). The effect of Simian virus 40 of the replication origin (SV40ori) deletion from pCAZ2 on transgene expression was also evaluated. RESULTS: pCAZ2 showed the highest LacZ expression in both skeletal muscle and heart in comparison with the CMV promoter-based vector 5 days after naked plasmid injection. LacZ expression in the heart obtained using 20 micro g of pCAZ2 was almost equivalent to that shown with AxCAZ3 at 6.0 x 10(9) optical particle units. The time course of transgene expression driven by CMV and CA promoters in the heart were similar, with the CA promoter providing significantly higher gene expression than the CMV promoter across all time points examined. SV40ori deletion from pCAZ2 did not affect transgene expression in either skeletal muscle or heart. CONCLUSIONS: Transgene expression mediated by naked CA promoter-based plasmid injection was shown to be quite efficient in the heart. We propose that the CA promoter vector is suitable for myocardial gene therapy.

Actins↗