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PubMedDate not supplied

Colocalization of Tie2, angiopoietin 2 and vascular endothelial growth factor in fibrovascular membrane from patients with retinopathy of prematurity.

PURPOSE: The tyrosine kinase receptor Tie2 and its ligands, the angiopoietins (Angs), play important roles in vascular integrity and neovascularization, modulating vascular endothelial growth factor (VEGF) activity. To elucidate the potential role of Angs and the Tie2 system in retinopathy of prematurity (ROP), we have investigated the expression of Angs, Tie2 and VEGF within fibroproliferative membranes in ROP. METHODS: Fibroproliferative membranes were obtained from 38 cases with stage 5 ROP at the time of vitrectomy. Membranes were fixed in formalin and embedded in paraffin. Each specimen was serially sectioned for immunohistochemistry. Polyclonal antibodies specific for Ang1, Ang2, Tie2 and VEGF were used for immunostaining. Immunoreactivity for von Willebrand factor (factor VIII) was also assessed to confirm the identity of vascular endothelial cells. RESULTS: Positive staining for Tie2 was observed in 23 of 38 specimens (60.5%). Tie2 was localized in vascularized regions of fibrovascular membranes and was co- expressed with VEGF and factor VIII. Ang2 stained positively in 18 of 38 (47.3%) serial sections where Tie2 was present, and was also co-expressed with VEGF and factor VIII. Ang1 was not generally observed in these specimens (3/38). CONCLUSIONS: VEGF and Ang2-Tie2 interactions may play an important role in the pathogenesis of ROP.

Angiogenesis Inducing Agents↗
PubMed1992

Markers of a hypercoagulable state following acute ischemic stroke.

BACKGROUND AND PURPOSE: The nature of hematologic disorders in different stroke subtypes remains uncertain. The purpose of this study was to clarify the differences in the coagulation and fibrinolytic activities among ischemic stroke subtypes. METHODS: We performed sequential measurements of hematologic parameters in 21 patients with acute cardioembolic stroke, 10 patients with atherothrombotic stroke, 23 patients with lacunar stroke, and 20 age-matched controls. RESULTS: A marked elevation of plasma concentrations of the thrombin-antithrombin III complex and crosslinked D-dimer was observed only in cardioembolic stroke within 48 hours of onset (p less than 0.01), persisting for one month with a gradual decline. In atherothrombotic stroke, however, the level of crosslinked D-dimer was not elevated at the onset, but increased seven days after onset (p less than 0.01). No significant changes in these marker levels were observed in lacunar stroke. CONCLUSIONS: Our findings suggest that the nature of altered coagulation and fibrinolysis are different in various subtypes of ischemic stroke, and that an assessment of these hematologic parameters may be useful for the early classification of these subtypes.

Acute Disease↗
PubMed1999

Increased serum levels of vascular endothelial growth factor in human crescentic glomerulonephritis.

OBJECTIVE: To investigate the serum levels of vascular endothelial growth factor (VEGF) in human crescentic glomerulonephritis (CRGN). METHODS: The serum VEGF levels in CRGN patients were compared with those in healthy subjects and in various types of glomerulonephritis. In addition, we investigated the relationship between serum VEGF levels and creatinine levels (Scr) and pathological parameters. RESULTS: The serum VEGF levels of the CRGN patients were significantly higher than in the healthy subjects and patients with MCNS, IgAN, and FGS. No correlation was found between serum VEGF levels and Scr in the RPGN patients. The serum VEGF levels in 6 CRGN patients had significantly decreased after 6 months of corticosteroid therapy. Moreover, there was a significant correlation between the serum VEGF levels and the crescent frequency or the grade of interstitial injury, and the rates of glomerular infiltration by macrophages. CONCLUSIONS: In the CRGN patients, severe glomerular and interstitial damages would result in increased serum VEGF levels and corticosteroid therapy may exert its efficacy through reduction of serum VEGF levels.

Adrenal Cortex Hormones↗
PubMed1990

[Well controlled comparative study in early rheumatoid arthritis with gold sodium thiomalate vs. auranofin].

RA Center Liaison Council conducted a comparative study of Auranofin and GST by envelope method on the patients with early RA who experienced the onset of the disease not more than two years ago. In final assessment of overall improvement, 57.9% of Auranofin-administered cases (22/38) showed moderate improvement or above. The comparable figure for GST group was 71.8% (28/39), but there was no statistically significant difference. Adverse reaction ADR incidence for Auranofin group was 12.2% (5/41), while 22.0% for GST (9/41), but the difference was not statistically significant. Drop out due to ADR was observed in 9.8% of Auranofin-administered cases and in 19.5% of GST-administered cases. The results of the study indicate that Auranofin is a most suitable DMARD than GST to be used for early RA, and GST is suitable for more active RA in view of its efficacy. But GST should be administered carefully because of its high ADR incidence.

Adolescent↗
PubMedDate not supplied

Biliary strictures in hepatic transplantation: treatment with self-expanding Z stents.

PURPOSE: To determine the long-term results of Gianturco-Rösch Z (GRZ) stent placement for the treatment of recurrent, benign biliary strictures in liver transplant recipients. MATERIALS AND METHODS: During a 5-year period, eight orthotopic liver transplant recipients underwent transhepatic placement of GRZ stents to treat 12 recurrent biliary strictures (six anastomotic, six intrahepatic). Prior treatment of 11 strictures with balloon dilation therapy had failed. Patients were followed up for 1-65 months. RESULTS: Stent placement was successful in all patients. Stent position remained stable in all but one patient. Three patients died (1, 25, and 28 months after stent placement), all with patent stents. Four patients required no further biliary intervention. Two of the other four patients needed intermittent biliary balloon dilation with removal of bile duct debris. The third patient had a stable, nonobstructing stenosis in the stent. The fourth passed his stents and needed no further intervention. CONCLUSION: GRZ stents are useful in patients who are refractory to repetitive balloon dilation of biliary strictures or who are poor surgical candidates.

Anastomosis, Surgical↗
PubMed2002

Magnetoencephalographic study of speed-dependent responses in apparent motion.

OBJECTIVES: There have been only few studies of visually-evoked cortical responses to apparent motion as a function of stimulus speed. Most earlier findings on evoked peak magnitudes and latencies, utilizing various types of smooth and apparent motion stimuli, have demonstrated that greater spatial separation/speed resulted in enhanced peak magnitudes, decreasing onset latencies in individual extrastriate neurons and in shorter motor reaction times in subjects. However, some reports using partial-coverage magnetoencephalography stated that increasing the stimulus displacement actually triggered a substantial reduction of the evoked main peak latency while the magnitude showed no clear change. METHODS: To resolve the issue of the dependency of evoked responses on stimulus speed in apparent motion, we presented moving bar stimuli to 6 subjects at velocities within a 100 fold range and investigated the ensuing evoked visual cortical activity using a whole-cortex magnetoencephalograph. The magnitude and the latency of the first major evoked peak M1 was measured and compared for 6 discrete bar-stimuli displacements in all subjects. RESULTS: Our results showed clearly that the M1 peak response magnitudes increased in a nonlinear way with higher apparent speeds (larger displacements), in compliance with the logarithmic Fechner law. We observed also that the fluctuations of the mean evoked M1 peak latency (140+/-10.6 ms) did not reach significance over the tested range of stimulus velocities. CONCLUSIONS: These findings probably reflect global motion processing mechanisms which rely on nonlinear speed-dependent feedback connectivity between striate and extrastriate visual cortex areas.

Adult↗
PubMed2005

Supplementation with tetrahydrobiopterin prevents the cardiovascular effects of angiotensin II-induced oxidative and nitrosative stress.

OBJECTIVE: The pteridine cofactor tetrahydrobiopterin (BH4) has emerged as a critical determinant of endothelial nitric oxide synthase (eNOS) activity. When BH4 availability is limited, eNOS does not produce nitric oxide (NO) but instead generates superoxide. BH4 may reverse endothelial dysfunction due to cardiovascular disease, including atherosclerosis, coronary artery disease and hypertension. In this study, the influence of BH4 on cardiovascular parameters and the production of free radicals following angiotensin II (Ang II) infusion was assessed. METHODS: BH4 (20 mg/kg per day in drinking water) was administered with Ang II (300 ng/kg per min subcutaneously, osmotic pump) for 7 days in Sprague-Dawley rats. In addition, BH4 was also given in vehicle-infused rats. RESULTS: Treatment with BH4 significantly prevented some of the effects of Ang II, such as impaired vascular responses to acetylcholine, hypertension and increases in heart weight index values. Treatment with BH4 also significantly reduced Ang II-induced increases in inducible NO synthase expression, nitrotyrosine immunostaining, NO production and superoxide anion formation in rats. CONCLUSION: These results indicate that BH4 might prevent the development of hypertension and myocardial hypertrophy, as well as the Ang II-induced production of superoxide and NO, thereby reducing the production of peroxynitrite. Therefore, BH4 may protect against the cardiovascular manifestations of oxidative and nitrosative stress in this experimental model of Ang II-mediated hypertension.

Acetophenones↗
PubMed2006

Identification of a novel autoantibody against pancreatic secretory trypsin inhibitor in patients with autoimmune pancreatitis.

OBJECTIVES: Although autoimmune pancreatitis (AIP) has been recently recognized as a new disease entity of chronic pancreatitis, the clinical diagnosis of the disease remains disputed. Autoantibodies against carbonic anhydrase II and lactoferrin are detected in most patients with AIP, but not in about 10%. We undertook this study to determine whether additional autoantibodies are present in the serum level of AIP patients. METHODS: We recruited 26 patients with AIP for the study. For comparison, we also recruited 53 patients with various pancreatic diseases and 12 healthy subjects. We immunoscreened human pancreatic cDNA library using patients' sera. Positive clones were analyzed by DNA sequencing and were constructed into a pGEX-4T-1 expression vector. The recombinant proteins were used as antigens in enzyme-linked immunosorbent assay to screen the subjects' sera for autoantibodies. RESULTS: We cloned a cDNA encoding the pancreatic secretory trypsin inhibitor (PSTI). Among 26 patients with AIP, autoantibodies against PSTI were significantly positive in 11 (42.3%) by western blotting and in 8 (30.8%) by enzyme-linked immunosorbent assay, respectively. However, none of control subjects was positive for anti-PSTI antibodies. CONCLUSIONS: These findings suggest that PSTI may be related to the pathogenesis of AIP, and autoantibodies against PSTI can be a useful diagnostic marker for the disease.

Aged↗
PubMed1997

Chronic angiotensin blockade with candesartan cilexetil in DOCA/salt hypertensive rats reduces cardiac hypertrophy and coronary resistance without affecting blood pressure.

To determine whether angiotensin II participates in the pathogenesis of cardiac hypertrophy and impairs coronary circulation in DOCA/salt hypertension, DOCA hypertensive rats were treated with candesartan cilexetil for 8 wk. DOCA/salt hypertension was induced in Wistar rats by removing the right kidney and subcutaneously injecting deoxycorticosterone acetate once a week. Control rats were given subcutaneous injections of saline and maintained on a normal diet. After 4 wk of observation, the angiotensin II receptor antagonist candesartan cilexetil was administered by oral gavage for 8 wk to 14 rats. Systolic blood pressure was measured weekly with the tail-cuff method. After 12 wk, the rats were killed and prepared. The isolated hearts were perfused by a Langendorff apparatus at constant flow. Perfusion pressure was measured by a small-volume transducer, and perfusion flow was recorded by a drop counter. Development of hypertension was not prevented by candesartan cilexetil treatment, but development of cardiac hypertrophy was inhibited. Minimum coronary vascular resistance (MCVR) obtained upon infusing adenosine into the isolated hearts was significantly higher in DOCA/salt hypertensive rats than in sham-operated controls. The elevated MCVR in DOCA/salt hypertensive rats was decreased by the administration of candesartan cilexetil for 8 wk. Thus, candesartan cilexetil regressed cardiac hypertrophy and improved coronary vascular resistance without affecting high blood pressure. These findings suggest that angiotensin II plays an important role in the pathogenesis of cardiac hypertrophy in DOCA/salt hypertension and that cardiac hypertrophy increases coronary vascular resistance.

Angiotensin Receptor Antagonists↗
PubMed1984

[Met-enkephalin-like immunoreactivity-containing nerve elements in the canine pancreas--a histochemical study].

Met-enkephalin-like immunoreactivity-containing nerve elements in the canine pancreas was investigated by immunocytochemistry. Anti-Met-enkephalin (Met-Enk) serum used as the primary anti-serum was raised against synthetic Met-Enk conjugated with bovine serum albumin by a glutaraldehyde method. For light microscopic immunocytochemistry, Bouin-fixed and paraffin-embedded sections not exceeding 20 micrometers in thickness were stained by the PAP method. For electron microscopy, the fixative used was 4% paraformaldehyde plus 1% glutaraldehyde in a 0.067 M phosphate buffer. Ultra-thin sections of Araldite-embedded materials were stained by a protein A-colloidal gold method. The main localization of Met-Enk-like immunoreactivity-containing nerve fibers and ganglion cell somas was as follows: a) on the surface of ganglion cell somas, b) among nerve fiber bundles in the connective tissue septum, c) around blood vessels in the exocrine parenchyma, and d) in the islet of Langerhans. Electron microscopic immunocytochemistry showed that colloidal gold particles representing a Met-Enk-like substance were concentrated on secretory type granules of the ganglion cell somas and nerve terminals around the blood capillaries. Met-Enk-like immunoreactivity was eliminated by preincubation of the primary anti-serum with Met-Enk (nerve fibers: 0.1 X 2(-3) g/l, ganglion cells: 0.1 X 2(-2) g/l of the diluted antiserum, 1:2000) before application to tissue sections. The functional significance of Met-Enk-like immunoreactivity-containing nerve elements in both the endocrine and exocrine pancreas was discussed.

Animals↗
PubMed1995

Effect of ileo-jejunal transposition on the growth of the GI tract and pancreas in young and aged rats.

BACKGROUND: Ileo-jejunal transposition (IJT; transposition of the distal quarter of the small intestine into the proximal jejunum) is known to stimulate mucosal growth of the transposed ileum, but the effects on other parts of the small intestine are controversial. The effect of aging on the trophic action of IJT is not known. METHODS: We examined the trophic effect of IJT (3 weeks post-operation) on the gastrointestinal tract and pancreas, and on plasma levels of neurotensin and gastrin in three different aged groups of Fischer 344 rats (4, 12, and 24 months old). RESULTS: Three weeks after IJT, the mucosal mass, villus height, and crypt depth increased significantly in the transposed ileum as well as in the remainder of the small intestine. The weights of the colon and pancreas increased significantly after IJT. These responses were not affected by aging. In each of the three age groups, IJT did not affect plasma gastrin level, but significantly increased plasma level of neurotensin. CONCLUSIONS: The distal ileum appears to play an important role in the regulation of growth in the intestine and pancreas; this role is preserved in aged rats. Neurotensin may play an important role in this mechanism.

Aging↗
PubMed2004

Relation between vertical orientation and stability of acetabular component in the dysplastic hip simulated by nonlinear three-dimensional finite element method.

In acetabular dysplasia, more vertical orientation of the acetabular component is often used to minimize the superolateral bone grafting. This study was designed to determine the effects of vertical orientation of the cup on the stability and polyethylene wear of the acetabular component in uncemented total hip arthroplasty (THA). Three-dimensional finite element models of the hemipelvis with dysplastic acetabulum were developed. Metal-backed hemispherical cups were placed in the true acetabulum with abduction angles of 35, 45, 55, and 65 degrees. It was found that more vertical orientation of the cup was associated with larger relative motion of the metal shell between the acetabulum and metal shell. Furthermore, tilting and torsional shear stresses in the model of the cup abduction angle of 65 degrees were found to be 1.7 times larger than that in the model with 35 degrees at the bone-metal shell interface. More vertically oriented cups caused larger contact stresses at the articulating surfaces of the polyethylene liners. The results suggest that the abduction angle of the acetabular component significantly influences cup loosening and polyethylene wear in THA.

Acetabulum↗
PubMed1999

Experimental small bowel transplantation using newborn intestine in rats: I. Lipid absorption restored after transplantation of nonvascularized graft.

BACKGROUND/PURPOSE: Utilizing the characters of neovascularized activity of newborn organs, the authors developed a rat model of small bowel transplantation with a free graft of newborn intestine into the recipient's omentum. METHODS: Segmental intestine from newborn rats were grafted into the omentum without vascular anastomosis in a syngeneic combination (n = 19). The transplanted intestine was examined morphologically and electrophysiologically 4 weeks after grafting. Then, recipients' small intestine was totally substituted by the transplanted newborn intestine, and recipients' survival was recorded after orthotopical reconstruction. During the experimental periods, feces of these rats were collected, and total lipid excretion was measured. The short-gut rats, whose small bowel was totally resected, served as a control (n = 12). RESULTS: Thirteen of 19 grafts (68.4%) were judged as a histologically mature intestine. They showed typical slow waves that were identical to those of native small intestine. After all of the mature grafts were interposed, six recipients (46.2%) survived longer than 15 weeks. Control short gut animals severely lost weight and died except for one. CONCLUSION: Newborn intestinal transplantation could restore severe weight loss in the short-gut rats and save them.

Animals↗
PubMed2000

A staining procedure for micronucleus test using new methylene blue and acridine orange: specimens that are supravitally stained with possible long-term storage.

The micronucleus test has been widely used as an in vivo cytogenetic test. It employs two different kinds of supravital staining methods which use either new methylene blue (N) and Giemsa (G) or acridine orange (AO). We have developed a new staining procedure for the preparation of specimens supravitally stained with possible long-term storage, using both N and AO. This N/AO-staining method involves three steps; (1) combination of the target tissue or target cells with an equivalent volume of 0.5% solution of new methylene blue (N-staining step), (2) immediate smear of the mixture, followed by treatment with methanol for 10 min for fixation and removal of N and drying (referred to as fixed-decolorized specimens), and (3) staining with 0.007% solution of AO for 3 min, followed by washing with Sörensen's buffer (pH 6.8) and covering of specimens before observation (AO-staining step). To examine whether the N/AO-staining method is useful for the micronucleus test, comparisons were made between N-, N/AO-, and AO-stained specimens prepared supravitally from peripheral blood of rats with and without treatment of cyclophosphamide. The results indicate that N/AO-stained specimens can be supravitally observed after long-term storage with the same coloration and comparable frequencies of micronucleated reticulocytes with a positive response as AO-stained specimens, if the staining process is temporarily stopped before AO-staining (as fixed-decolorized specimens), or if the AO-staining step is repeated. The results also showed that separated reticulocyte types are supravitally stained in a similar fashion to N-stained specimens but not to AO-stained specimens, indicative of the preservation of the supravital feature of N-staining. Taken together these results suggest that the N/AO-staining procedure could offer an additional useful staining tool for the micronucleus test.

Acridine Orange↗
PubMed1999

Effect of surface roughness on proliferation and alkaline phosphatase expression of rat calvarial cells cultured on polystyrene.

Rough-surfaced substrates made by a variety of methods have been shown to influence osteoblast proliferation and differentiation. The purpose of this study is to confirm the role of surface roughness in promoting osteoblastic differentiation using tissue culture polystyrene as substrate, by excluding factors other than roughness. Immature osteogenic cells derived from fetal rat calvariae were cultured on the plastic cover strips having varied degrees of roughness created by treatment with four kinds of grinding paper of different particle sizes. The proliferation and gene expression of alkaline phosphatase (ALP) and osteocalcin of the calvarial cells increased on the rough-surfaced cover strips. These levels increased in response to the increase in the degree of surface roughness up to 0.8 microm of average roughness and then decreased to the level observed for the smooth surface. These results demonstrate that the surface roughness itself caused increases in osteoblastic proliferation and differentiation in cell cultures.

Alkaline Phosphatase↗
PubMed2003

Prevalence of self-perceived auditory problems and their relation to audiometric thresholds in a middle-aged to elderly population.

OBJECTIVE: Hearing loss has been identified as one of the most frequent conditions affecting the elderly population. The purpose of this study was to provide estimates of the prevalence of self-perceived hearing problems in a middle-aged to elderly general population and to make a comparison among generations and between genders regarding the relationship between audiometric measurements and hearing problems. MATERIAL AND METHODS: The study was conducted using a population-based sample of 2150 adults, aged 40-79 years, who participated in the Longitudinal Study of Aging conducted by the National Institute for Longevity Sciences between 1997 and 2000. A questionnaire on hearing problems was administered and pure-tone audiometry was conducted. RESULTS: A third of subjects in their 40s and half of the subjects aged > 60 years were aware of having difficulty hearing. The audiometric thresholds in both the better and worse ears were associated with self-perceived hearing difficulty in all age groups. Statistically significant age and gender differences were observed in each respondent group. The older group tended to underestimate their hearing difficulty in comparison with the younger group, and males tended to underestimate their hearing difficulty more than females. CONCLUSION: These results may contribute to the development of an intervention strategy for auditory rehabilitation for the middle-aged and elderly populations.

Adult↗
PubMed2006

Steroid pulse therapy impaired endothelial function while increasing plasma high molecule adiponectin concentration in patients with IgA nephropathy.

BACKGROUND: Decreased plasma adiponectin is associated with impaired endothelial function and, thereby, increased risk for cardiovascular events. Glucocorticoid (GC) affects vascular endothelial cells either favourably or harmfully depending upon the dosages and duration. We examined the effect of GC pulse therapy on vascular endothelial function. METHODS: Fourteen young patients with IgA nephropathy were evaluated for flow-mediated vasodilation (FMD), plasma levels of adiponectin both in high molecular weight (HMW adiponectin) form and in single molecular form (total adiponectin), hepatocyte growth factor (HGF), asymmetric dimethylarginine (ADMA), and high-sensitive C-reactive protein, before and after a course of GC pulse therapy. RESULTS: GC pulse therapy significantly decreased FMD (from 7.2 +/- 2.6 to 5.7 +/- 2.5%, P < 0.01). Meanwhile, plasma adiponectin levels were significantly augmented (total adiponectin: from 10.2 +/- 4.0 to 12.1 +/- 6.3 microg/ml, P < 0.05; HMW: from 6.5 +/- 3.2 to 7.7 +/- 3.3 microg/ml, P < 0.05). In parallel, elevated concentrations of serum HGF (from 0.28 +/- 0.12 to 0.63 +/- 0.38 ng/ml, P < 0.01) and plasma ADMA (from 0.45 +/- 0.07 to 0.53 +/- 0.04 nmol/ml, P < 0.05) were observed. CONCLUSIONS: GC pulse therapy impaired endothelial function while increasing plasma adiponectin levels, which may in turn restore the endothelial function in patients with IgA nephropathy.

Adiponectin↗
PubMed1994

[Acidified aspirin-induced gastric lesion in rats with hepatic cirrhosis produced by N-nitrosodiethylamine or carbon tetrachloride. Effect of aldioxa on gastric lesions].

Gastric lesion was induced by the oral administration of acidified aspirin in rats with hepatic cirrhosis produced by N-nitrosodiethylamine (NDA) or carbon tetrachloride (CCl4). Gastric lesion by acidified aspirin was aggravated in NDA-induced cirrhosis, but not in CCl4-cirrhotic rats. To clarify this difference in the susceptibility of the gastric mucosa, gastric mucosal blood flow and gastric emptying were measured by the hydrogen gas clearance method and beads method, respectively. Gastric mucosal blood flow was lower and gastric emptying was significantly delayed in NDA-induced cirrhotic rats as compared with the controls, but not in CCl4-induced cirrhotic rats. Gastric mucosal blood flow in NDA-induced cirrhotic rats was significantly decreased by the oral administration of acidified aspirin as compared with the controls. Aldioxa dose-dependently inhibited the gastric lesion formation by acidified aspirin and inhibited the decrease of gastric mucosal blood flow in NDA-induced cirrhotic rats. These results suggest that aggravation of gastric lesion induced by acidified aspirin in NDA-induced cirrhotic rats would be due to the decrease of gastric mucosal blood flow and delay of gastric emptying. In addition, aldioxa showed a protective effect against gastric lesions induced by acidified aspirin in NDA-induced cirrhotic rats, suggesting that this compound would have an inhibitory effect on gastric lesions that are accompanied by hepatic cirrhosis.

Allantoin↗