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Activated leucocytes express and secrete macrophage inflammatory protein-1alpha upon interaction with synovial fibroblasts of rheumatoid arthritis via a beta2-integrin/ICAM-1 mechanism.

OBJECTIVE: To examine the expression and regulation of chemotactic factor, macrophage inflammatory protein-1alpha (MIP-1alpha) by fibroblast-like synoviocytes (FLS), monocytes and polymorphonuclear neutrophils (PMN) isolated from the synovial fluid (SF) of rheumatoid arthritis (RA) patients. METHODS: Monocytes or PMN obtained from RA SF were co-cultured with unstimulated semiconfluent RA FLS. Culture supernatants were assayed for MIP-1alpha by enzyme-linked immunosorbent assay. The expression of MIP-1alpha mRNA and protein was also determined by Northern blot analyss and immunohistochemistry respectively. RESULTS: Interaction of activated leucocytes with FLS synergistically increased MIP-1alpha expression and secretion via a mechanism mediated by beta2-integrin/ intercellular adhesion molecule 1. CONCLUSION: MIP-1alpha expression within inflamed joints appears to be regulated not only by inflammatory cytokines but also by the physical interaction of activated leucocytes and FLS, and plays a crucial role in the progression and maintenance of RA synovitis.

Arthritis, Rheumatoid↗

The effect of neoadjuvant androgen suppression on prostate cancer-related outcomes after high-intensity focused ultrasound therapy.

OBJECTIVE: To explore the effect of neoadjuvant androgen suppression (AS) compared to no AS on cancer-related outcomes after radical high-intensity focused ultrasound (HIFU) therapy for men with presumed organ-confined prostate cancer. PATIENTS AND METHODS: Between January 1999 and January 2005, 250 patients underwent HIFU for presumed localized adenocarcinoma of the prostate; 154 had received neoadjuvant hormonal therapy and 96 had not. The primary outcome measure was treatment failure, as defined by the presence of prostate cancer on the biopsy taken 6 months after HIFU. Multiple logistic regression was used to examine relationships between the use of HIFU with and with no neoadjuvant AS and treatment failure. RESULTS: The treatment failure rate was slightly lower in patients receiving neoadjuvant AS (31% vs 34%), but this was not statistically significant (P = 0.119). CONCLUSION: In this unrandomized comparison between neoadjuvant or no AS before HIFU for men with presumed organ-confined prostate cancer, there appeared to be little if any benefit associated with the previous administration of AS.

Adenocarcinoma↗

Injuries in elite motorcycle racing in Japan.

OBJECTIVES: To investigate the incidence and pattern of injuries, relative risks, and factors affecting incidence among elite motorcycle competitors in Japan. METHODS: A total of 117 elite motorcycle competitors including 36 road racers, 60 motocross racers, and 21 trial bike riders completed a questionnaire about injuries. RESULTS: Sixty major injuries (25 in road racing, 32 in motocross, and three in trial bike riding) were reported. The most common injuries were fractures (45), followed by ligament injuries (8), dislocations (5), and soft tissue injuries (2). The overall injury rate was 22.4 per 1000 hours, and the death rate was zero. There was no significant correlation between risk of injury and age, experience, or accumulated competition points. CONCLUSIONS: Injury rates in competitions such as road racing and motocross are high, and therefore additional safety measures are needed to protect competitors from injury.

Adult↗

Cadaveric renal transplantation from a non-heart-beating pediatric donor into adult recipients.

INTRODUCTION: The use of cadaveric pediatric kidneys has been suggested as a means to overcome organ shortage, but is debated because of technical complications and an increased incidence of functional allograft impairment. METHODS: We experienced 2 cases of cadaveric renal transplantation from a non-heart-beating pediatric donor. RESULTS: In our cases, transplanted kidneys achieved good graft function and proteinuria due to glomerulosclerosis was not recognized. CONCLUSION: Previous reports indicate that in transplantation from pediatric donors into adults recipients, glomerular sclerosis occurs as the reason for impairment of grafts. Further, cadaveric renal transplantation from a non-heart-beating donor has a warm ischemia time and an increased risk of hyperfiltrated injury and graft failure. If transplantation of pediatric kidneys into adults from a non-heart-beating donor is performed, BMI and BSA must be carefully considered in the selection of recipients in order to avoid imbalance between nephron supply and metabolic demands and to insure successful, healthy grafts.

Body Mass Index↗

[The mechanism of biochemical modulation in methotrexate/5-fluorouracil sequential chemotherapy].

5-fluorouracil (5-FU)/methotrexate (MTX) sequential chemotherapy is one of the standard regimen for the treatment of gastric cancer. Though this combination therapy is highly effective, the mechanism is still unclear. In this study, we investigated the relationship between antitumor activity and the inhibition of thymidylate synthase and between antitumor activity and incorporation of 5-FU into RNA (F-RNA) in mice bearing Sarcoma-180 treated by tegafur alone (100 mg/kg) or by the combination of MTX (42 mg/kg) and tegafur (100 mg/kg). A new method for the determination of F-RNA of tumor tissue samples was used. Briefly, RNA fractions containing incorporated 5-FU were extracted by KOH hydrolysis. FUra in RNA fractions was released by HCl hydrolysis and its levels were determined by GC-MS. The results showed that the F-RNA levels were significantly elevated by the pretreatment of MTX. According to this result, it is suggested that the measurement of F-RNA levels together with the determination of FUra concentration and the inhibition rate of thymidylate synthase were considered as a good means for the evaluation of antitumor efficacy of FUra. We concluded that the impairment of RNA metabolism played a major role in the antitumor activity of MTX/5-FU combination.

Animals↗

Effects of nipradilol on venous hemodynamics: evaluation with a Doppler blood flow method.

Nipradilol is a newly synthesized beta-blocker which has a propranolol-like structure and contains a nitrate moiety. To examine the effect of nipradilol on venous blood flow, a single oral dose of nipradilol (6 mg) and propranolol (20 mg) was administered in the same 15 normal volunteers on separate days. Peak flow velocities, flow velocity integrals, and the diameter of the right brachiocephalic vein were measured before and 2 h after drug administration using Doppler echocardiography. These two beta-blockers significantly decreased systolic blood pressure to the same extent as they did heart rate. Nipradilol dilated the venous diameter by 8% and decreased peak flow velocity by 8% during systole and 9% during diastole. The flow velocity integral in one cardiac cycle also decreased significantly by 14%. Propranolol, however, failed to modify these parameters. These results suggest that nipradilol decreased venous return through its nitroglycerin-like direct vasodilating action.

Adult↗

[Surgical stress in perioperative period of combined off-pump coronary artery bypass grafting and abdominal aortic aneurysm repair].

OBJECTIVES: It is still controversial whether we should choose simultaneous operation or two-staged operation for patients who need both coronary artery bypass grafting (CABG) and abdominal aortic aneurysm (AAA) repair. Some reports suggest that combined CABG without cardiopulmonary bypass and AAA repair is less invasive than those with cardiopulmonary bypass. We estimated surgical stress of combined off pump CABG and AAA repair (CABG + AAA) in perioperative period compared with simple AAA repair retrospectively. METHODS: Seven patients (mean 60 years) underwent simultaneous operation of off pump CABG and AAA repair in our institution. We gathered data associated with circulatory, respiratory, renal function, recovery, and so on. We also examined postoperative complication and mortality. RESULTS: All parameters, except operation time and amount of catecholamine used, were not significantly different between the two groups. There were no operative mortality and only a slight morbidity in CABG + AAA. CONCLUSIONS: Our findings suggest that careful circulatory management with adequate transfusion and catecholamine use under precise monitoring is necessary during operation, but recovery after surgery, complication, and mortality in this combined operation are almost equivalent to those of simple AAA repair. We suggest that combined operation of CABG and AAA repair can be performed effectively.

Aged↗

Tumor growth suppression by a retroviral vector displaying scFv antibody to CEA and carrying the iNOS gene.

BACKGROUND: In a recent in vitro study we demonstrated a specifically-targeted killing of CEA-expressing cells by a recombinant bifunctional retrovector displaying an scFv antibody to CEA and carrying the iNOS gene. In this study, we tested whether a gene therapy using the recombinant retrovirus could inhibit the growth of CEA-expressing tumors in mice. MATERIALS AND METHODS: SCID mice were inoculated s.c. on the back with CEA-expressing MKN-45 cells on day 0. The recombinant viral particles were injected into the inoculated sites on days 3, 5 and 7 and tumor size was measured every 5 days. RESULTS: The s.c. administration of the recombinant retrovirus produced a marked growth inhibition of MKN-45 tumors in SCID mice. When the actual tumor weights were measured 50 days after initiation of treatment, about 70% reduction was observed in the treated group as compared to the control groups. CONCLUSION: This approach may also be applied to other tumor antigens expressed on cancer cells and is a step towards the cell specific suppression of tumorigenicity.

Animals↗

Evaluation of lumbar spine fusion. Plain radiographs versus direct surgical exploration and observation.

STUDY DESIGN: In a retrospective study, the incidence of false positive and false negative interpretation of x-rays for solid spinal arthrodesis with spinal instrumentation was evaluated in 75 patients. OBJECTIVE: To evaluate the accuracy of the interpretation of x-rays for diagnosing solid spinal arthrodesis in patients with spinal instrumentation. SUMMARY OF BACKGROUND DATA: This retrospective study compared spinal fusion, as determined by direct observation and radiographic evaluation, in 75 patients with instrumented lumbar fusions using multiple devices. The fusions included posterolateral fusions or posterolateral with interbody fusions. Autograft, allograft, and a combination of these also were used. METHODS: A single blinded examiner reviewed all x-rays immediately before the spinal hardware was removed and the fusion mass was explored by the surgeon. RESULTS: There was a positive correlation between x-rays and the observations at the time of surgery in only 68% of the patients. CONCLUSION: This study indicates that the accuracy of x-ray interpretation for spinal arthrodesis is only 68%. The L4-L5 level was the most difficult level to fuse and the most difficult to interpret using x-rays. Patients with persistent back pain, when nonmechanical causes have been ruled out, should be considered for surgical exploration of the fusion mass even if x-rays appear to indicate a solid fusion.

False Negative Reactions↗

Multi-site interventional real-time procedure demonstrations with the use of integrated services digital network connections.

PURPOSE: To evaluate the effectiveness and cost of commercially available video conferencing units and standard Integrated Services Digital Network (ISDN) connections for real-time multi-site transmissions of interventional procedures. METHODS: A network of five separate interventional radiology departments-three in the Czech Republic and one each in Austria and the USA-was established using Polyspan (Polycom in the USA) View Stations and ISDN connections. This network was used for transmissions of 16 live interventional procedures to the Sixth International Workshop on Interventional Radiology in Prague, Czech Republic in June 2000. RESULTS: The transmissions were successful and of sufficient quality to contribute to the educational success of the workshop. The cost of the ISDN transmissions was a fraction of satellite transmission costs. CONCLUSION: Multi-site real-time interventional procedure transmissions using video conferencing Polyspan (Polycom) View Stations and ISDN connections are a promising means of improving interventional tele-education and decreasing its cost.

Austria↗

Puromycin aminonucleoside induces apoptosis and increases HNE in cultured glomerular epithelial cells(1).

Puromycin aminonucleoside induces apoptosis and increases 4-hydroxy-2-nonenal (HNE) in cultured glomerular epithelial cells. We have previously reported the detachment of cultured glomerular epithelial cells (GECs) from their substrata by puromycin aminonucleoside (PAN) treatment. In this study we explored whether or not apoptosis was involved in the mechanisms of the detachment. DNA fragmentation on gel electrophoresis was clearly shown by 10(-3) M PAN treatment of GECs. Nuclear staining by Hoechst 33342 indicated the greatest number of apoptotic cells at 10(-3) M PAN for 48 h treatment. Similarly, TUNEL methods revealed maximal apoptotic cells at 10(-3) M PAN for 48 h treatment. Caspase-3 (like) protease activity increased at 10(-3) M PAN, and decreased at 2 x 10(-3) M PAN for 48 h treatment as well as at 10(-3) M PAN for 60 h treatment. Pretreatment with 2'-deoxycoformycin (DCF), inhibitor of adenosine deaminase, abolished these effects of PAN on cultured GECs. PAN treatment increased HNE, a lipid peroxide adduct, modified protein in cultured GECs, which was also prevented by pretreatment by DCF. These results for the first time indicate that the PAN-induced detachment of GECs from culture substrata is mediated at least in part through apoptosis via oxidative stresses by adenosine deaminase activity.

Adenosine Deaminase Inhibitors↗

Lack of suitability of the rabbit model for particulate uterine artery embolization.

PURPOSE: The goal of this study was to evaluate the rabbit model for studies of particulate uterine artery embolization (UAE). Rabbits were chosen because it was believed that their year-round breeding time and short duration of pregnancy would be useful in studies of fertility and pregnancy after UAE. MATERIALS AND METHODS: Bilateral UAE was performed in 12 adult female New Zealand White rabbits weighing 4-5.2 kg. All animals were proven to be breeders before treatment. Each uterine artery was embolized to stasis with use of 180-300- microm polyvinyl alcohol (PVA) particles (n = 9 animals), 500-710- microm PVA particles (n = 1), or tris-acryl 500-700- microm gelatin microspheres (n = 2). RESULTS: Two rabbits died 7 days after embolization and the other 10 rabbits had to be killed because of malaise and weight loss 4-8 d after embolization. In all animals, necropsy demonstrated extensive uterine necrosis sparing only the tip of the uterine horn. CONCLUSION: Rabbits are an unsuitable model for studies of UAE with the embolic agents in clinical use.

Angiography↗

Pathogenic role of thromboxane A2 in immediate food hypersensitivity reactions in children.

BACKGROUND: Food hypersensitivity, from the standpoint of pathogenesis as well as clinical management, remains controversial. During the food allergen-induced immediate hypersensitivity reaction, various chemical mediators are released. OBJECTIVE: The purpose of our study was to determine whether thromboxane A2 participates in food antigen-induced responses in children with food hypersensitivity. METHODS: Nine open food challenges were performed in nine patients with suspected food hypersensitivity. Plasma thromboxane B2 and histamine levels were measured during a 24-hour period following the challenge. RESULTS: All the patients demonstrated immediate reactions after food challenge. The mean plasma thromboxane B2 level (a marker of thromboxane A2 activity) rose significantly at two hours and three hours after the challenge. Simultaneously, the mean plasma histamine level rose significantly at two hours and three hours after the challenge. CONCLUSIONS: The results suggest that thromboxane A2 may play a pathogenic role in part in the immediate reaction after food challenge and that thromboxane A2 is probably released from a common cellular source (eg, mast cell) with histamine and/or by a common mechanism (eg, IgE-dependent platelet activation).

Child↗

Preparation and characterization of polylactic acid microspheres containing water-soluble dyes using a novel w/o/w emulsion solvent evaporation method.

Polylactic acid (PLA) microspheres containing soluble dyes as water-soluble model compounds were prepared using the water-in-oil-in-water (w/o/w) emulsion solvent evaporation method. Addition of electrolytes such as NaCl or CaCl2 into the external aqueous phase significantly improved brilliant blue (BB) entrapment efficiency compared to the case of no additives. NaCl was the most effective for obtaining high entrapment efficiency (80-90% of theoretical BB content). The average diameter of the obtained microspheres was in the region of 10-20 microns in all cases. PLA microspheres containing 5 and 10% (w/w) BB exhibited the so-called burst release. The release rate decreased with decrease in the internal aqueous droplet volume in the preparation process. In particular, with PLA microspheres containing 5% (w/w) BB, those prepared with the smallest internal droplet volume (63 microliter), the initial burst release was reduced significantly, and 50% (w/w) of the loaded BB remained in the microspheres for 7 days.

Benzenesulfonates↗

Effect of quinine solutions on intracellular Ca2+ levels in neuro-2a cells--conventional physiological method for the evaluation of bitterness.

The purpose of the present study was to examine the effect of quinine on intracellular Ca2+ ([Ca2+]i) levels in cultured neuro-2a cells, and to investigate the possibility of using [Ca2+]i levels to predict the bitterness of quinine solutions. [Ca2+]i levels in neuro-2a cells increased following stimulation by quinine in a concentration-related manner. There was a good linear correlationship between the quinine-induced increase in [Ca2+]i levels increase and the bitterness scores of the quinine solutions as assessed in human gustatory sensation tests (r2=0.918). The quinine-induced increase in [Ca2+]i levels was inhibited by thapsigargin (an inhibitor of the Ca2+ pump into intracellular stores), U73122 (an inhibitor of phospholipase C) and omega-conotoxin (an N-type Ca2+-channel blocker), but not by nifedipine (an L-type Ca2+-channel blocker).

Adult↗

Quantitative analysis of liver fibrosis and stellate cell changes in patients with chronic hepatitis C after interferon therapy.

OBJECTIVE: The proliferation and differentiation of stellate (Ito, or fat-storing) cells into myofibroblast-like cells is responsible for the development of liver fibrosis. Using computer image analysis, we evaluated the changes of alpha smooth muscle actin-positive stellate cells and liver fibrosis after interferon-alpha or -beta (IFN-alpha, beta) therapy in patients with chronic hepatitis C. METHODS: Patients with chronic hepatitis C were treated with IFN-alpha or -beta and were divided into three groups on the basis of clinical criteria; a complete responder group (CR, 18 of 51), a partial responder group (PR, 17 to 51), and a nonresponder group (NR, 16 of 51). Liver fibrosis was assessed from specimens stained with Sirius red and was quantitated by computer image analysis. We also evaluated alpha-smooth muscle actin expression in the liver before and after IFN therapy by a semiquantitative scoring method (the alpha-smooth muscle actin index). RESULTS: Before IFN therapy, a large number of stellate cells expressing a-smooth muscle actin were present in the liver biopsy specimens. There was a significant correlation (r = 0.699, p < 0.05) between the change in the percent area of fibrosis and the alpha-smooth muscle actin index before and after IFN therapy in all groups. The complete responder group also showed a significant reduction of a-smooth muscle actin-expressing cells that was correlated with the reduction of serum ALT (r = 0.686, p < 0.05). CONCLUSION: These results suggest a-smooth muscle actin-expressing cells are responsible for liver fibrosis, and the elimination of factors stimulating matrix synthesis (e.g., hepatitis virus) may decrease liver fibrosis.

Actins↗

Change in formation of gastric lesions by aspirin during aging in rats.

Formation of gastric lesions induced by orally administered aspirin (100 mg/kg) was examined in 4 to 86 week-old Sprague-Dawley male rats. Gastric mucosal prostaglandin I2 level and gastric secretion in basal state were also examined in these rats. Gastric mucosal PGI2 level was measured by bioassay and gastric secretion was collected by the pyloric ligation method for 4 h. Gastric lesions reached the maximum value in 7 week-old, and lowest in 60 week-old. Acid output also reached the maximum value in 7 week-old. As for PGI2 level, it showed the maximum value in 20 week-old, and moderately decreased thereafter. In 86 week-old, PGI2 level was further lowered to about 35% of 20 week-old rats. A linear positive correlation was noted between formation of aspirin-induced gastric lesion and acid secretion. From these results, it was concluded that formation of gastric lesions by aspirin was closely related to acidity of the gastric secretion. It was also suggested that in aged rats, aspirin-induced gastric lesions may at least partly be associated with the reduced PGI2 level.

Aging↗

A 10-year follow-up study of renal transplant recipients treated with cyclosporine. Japanese Cyclosporine Kidney Transplant Study Group.

AIM: In this report a 10-year follow-up of Japanese multicentre trial of renal transplantation using cyclosporine is described. MATERIAL AND METHODS: A total of 1,323 recipients, including 1,055 (79.7%) living donor (LD) transplantations and 268 (20. 3%) non-heart-beating cadaveric donor (CD) transplantations, were enrolled in the study. RESULTS: Favorable results; graft survival at 1, 5 and 10 years were 95.8%, 80.9%, 56.8%, respectively, for LD, and 88.7%, 74.2%, 58.8%, respectively, even for CD, were obtained. No serious adverse reactions or complications were observed in this group of patients excepting 28 cases (2.0%) of malignant tumors. There were no cases of abnormality in 49 babies delivered during the term. CONCLUSION: We demonstrate the interesting findings that graft survival of non-heart-beating CD are surprisingly as good as that of LD and the safety issues are almost equal to other available data in other countries.

Adult↗