Association of Vascular Endothelial Growth Factor Expression with Tumor Angiogenesis and with Early Relapse in Primary Breast Cancer

Angiogenesis is an independent prognostic indicator in breast cancer. In this report, the relationship between expression of vascular endothclial growth factor (VEGF; a selective mitogen for endothelial cells) and the microvessel density was examined in 103 primary breast cancers. The expression of VEGF was evaluated by immunocytochemical staining using anti-VEGF antibody. The microvessel density, which was determined by immunostaining for factor VIII antigen, in VEGF-rich tumors was clearly higher than that in VEGF-poor tumors ( P <0.01). There was a good correlation between VEGF expression and the increment of microvessel density. Furthermore, postoperative survey demonstrated that the relapse-free survival rate of VEGF-rich tumors was significantly worse than that of VEGF-poor tumors. It was suggested that the expression of VEGF is closely associated with the promotion of angiogenesis and with early relapse in primary breast cancer.     

Cyclosporine overcomes cold preservation/reperfusion injury of liver graft: Chemokine release and liver ultrastructure

There is a growing body of evidence that the cytokine, tumor necrosis factor-α (TNF-ga), plays an important role in the development of hepatic ischemia/reperfusion injury. We found that the immunosuppressants, cyclosporine-A (CsA), azathioprine, and FK506, have protective effects on such injury. The purpose of the present study was to elucidate mechanisms involved in these beneficial effects of the immunosuppressant, CsA, on liver injury following cold preservation and transplantation, with special reference to the suppression of TNF-α release. Rat livers were stored in Euro-Collins solution (EC) at 4°C for 6h and orthotopically transplanted. The animals allotted to two groups: group A (untreated controls) and group B (CsA pretreatment of recipients). CsA (10 mg/kg, p.o.) was given for 3 consecutive days preoperatively. CsA pretreatment of the recipients significantly improved the 2-week survival rate (0/6 for group A, 3/6 for group B;P<0.05) and this was associated with a significant decrease in serum TNF-α levels 2h posttransplantation (group A, 69.8±15.7 pg/ml; group B, 22.8±6.8; mean±SEM;n=12 each;P<0.05) and amelioration of sinusoidal endothelial injury, assessed by electron microscopy. Plasma endotoxin levels following reperfusion of the grafts were not altered by the CsA therapy. Morphologically, CsA pretreatment of the recipients did not alter activation of Kupffer cells. CsA pretreatment of the recipient aids in preventing cold preservation/reperfusion injury of the liver graft, possibly by modulating effects of TNF-α.     

Preoperative identification of subthalamic nucleus for deep brain stimulation using three-dimensional phase sensitive inversion recovery technique.

PURPOSE: We assessed the feasibility of utilizing three-dimensional (3D) phase sensitive inversion recovery (IR) images for preoperatively determining deep brain stimulator position. METHODS: We measured geometric distortion with a grid phantom and evaluated images of 3 volunteers to determine optimum imaging parameters for 3D phase sensitive IR. RESULTS: Geometric distortion measured less than 1.0%. Respective inversion and recovery times, which provided high T(1) contrast between the subthalamic nucleus and adjacent tissue, were 200 and 4000 ms. In studies of 3 volunteers and 2 patients, the subthalamic nucleus was clearly depicted in 3D phase sensitive IR images. The measured coordinates of the subthalamic nucleus agreed well with those calculated by conventional estimation from midpoint of the anterior and posterior commissure. CONCLUSION: Three-dimensional phase sensitive inversion recovery was useful in visualizing the subthalamic nucleus for effective deep brain stimulation.     

Intense and prolonged Tl-201 accumulation in a slow growing bronchioloalveolar carcinoma

Thallium-201 SPECT was performed to evaluate a pulmonary lesion in a 73-year-old male which had been considered to be an inflammatory lesion for two years. The lesion has slowly increased in size on x-CT. Tl-201 was intensely taken up and retained in the lesion, suggesting a malignant lesion. Histological examination revealed that the lesion was bronchioloalveolar carcinoma. This case suggested that Tl-201 uptake of pulmonary carcinoma would not be necessarily related to cell growth rate.     

Procedures to Characterize In Vivo and In Vitro Enantioselective Glucuronidation Properly: Studies with Benoxaprofen Glucuronides

The diastereoisomeric glucuronic acid conjugates of R/S-benoxaprofen are the major benoxaprofen metabolites and are found in urine at high concentrations. The conjugates of R- and S-benoxaprofen can be separated directly on a C₁₈ reversed-phase column using a mixture of acetonitrile and tetrabutylammonium hydroxide buffer, pH 2.5 (28:72, v/v), as the mobile phase. The k values of S- and R-benoxaprofen glucuronides are 57.5 and 63.0, respectively. Diluted urine or deproteinized plasma samples were injected without further treatment. With fluorescence detection at 313/365 nm, quantifiable limits of 50 ng equiv./ml were found for the conjugates. The intra- and interday variability was below 12%. Utilizing this analytical procedure it is possible to characterize enantioselective glucuronidation both in vivo and in vitro. For in vitro procedures, apparent rates of formation and the R/S ratio may be substrate (benoxaprofen) and cosubstrate (UDPGA) dependent. Moreover, enantioselective cleavage of the formed benoxaprofen glucuronides by alkaline hydrolysis, hydrolytic enzymes, and acyl migration must be controlled for both in vitro and in vivo studies since R-benoxaprofen glucuronide is degraded faster than the S-diastereomer under certain conditions.     

Catalase, a Specific Antigen in the Feces of Human Subjects Infected with Helicobacter pylori

Recently, we reported the production of three new monoclonal antibodies with high specificity for a Helicobacter pylori antigen suitable for diagnosis of H. pylori infection. The aim of the present study was to identify the antigen recognized by these monoclonal antibodies concerning both H. pylori and the feces of human subjects infected with H. pylori. The cellular antigen was purified from an H. pylori cell extract by immunoaffinity column chromatography with the monoclonal antibody as a ligand. The amino-terminal amino acid sequences (eight residues) of the purified antigen and H. pylori catalase were the same. The molecular weights of native and subunit, specific catalase activity, and UV and visible spectra of the purified antigen were in good agreement with those of H. pylori catalase. The human fecal antigens were purified from two fecal samples of two H. pylori-positive subjects by ammonium sulfate precipitation, CM-Sephadex C₅₀ chromatography, and the same immunoaffinity chromatography used for the H. pylori cellular antigen. The fecal antigens had catalase activity. The amino-terminal amino acid sequences (five residues) of the human fecal antigen and H. pylori catalase were the same. The monoclonal antibodies reacted with the native cellular antigen, but did not react with the denatured antigen, human catalase, and bovine catalase. The results show that the target antigen of the monoclonal antibodies is native H. pylori catalase and that the monoclonal antibodies are able to specifically detect the antigen, which exists in an intact form, retaining the catalase activity in human feces.     

Interruption of the lordosis reflex of female rats by ventral midbrain stimulation.

The lordosis reflex, dorsiflexion of the vertebral column, is an estrogen-dependent, essential element of female sexual behavior in rodents. Unilateral electrical stimulation of the midbrain ventral tegmental area through a chronically implanted electrode in freely moving, estrogen-primed ovariectomized female rats caused a rapid and strong suppression of the lordosis reflex in response to either male mounts or manual cutaneous stimuli. The interruption occurred in a graded manner to increased stimulus intensity, with a threshold at 30 microA. The optimal frequency was at 75-125 Hz. After the termination of electrical stimulation, lordosis performance returned promptly to the pre-stimulation level. No aversive response accompanied the blockade of lordosis. Electrical stimulation specifically blocked lordosis, without disrupting the proceptive components of female sexual behavior. In 10 animals tested, concomitant injection of dopamine receptor blocker pimozide tended to offset the effects of electrical stimulation in 2 cases. Interruption of the lordosis reflex might be mediated by projections from the ventral tegmental area, which activate a descending pathway inhibitory to the lordosis reflex arc at or below the lower brain stem.