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.     

Bladder function in elderly men with subclinical brain magnetic resonance imaging lesions.

Among 43 men more than 60 years old who complained of urinary irritative symptoms 40 had subclinical lesions in the brain on magnetic resonance imaging (MRI). Of these 40 patients 23 (57.5%) had detrusor hyperreflexia. The mean age of the patients with and without detrusor hyperreflexia was 75.8 and 68.2 years, respectively, which is a statistically significant difference. Patients with detrusor hyperreflexia were more likely to have lesions of the basal ganglia than patients without detrusor hyperreflexia. This study suggests that detrusor hyperreflexia, subclinical MRI lesions in the brain and aging are intimately interrelated.     

Experimental models of reflex contractile activity in the rabbit bladder

We were able to produce two highly reproducible experimental models (in the rabbit) that demonstrated a high degree of reflex bladder contractile activity. In one model, a somatovesical reflex was induced by touching or pinching the perineal area. This reflex may be organized through a neurogenic reflex at the spinal level. In another model, rhythmic bladder contractions were produced by distal urethral constriction in the absence of bladder distension. These rhythmic contractions were thought to be due to a supraspinal reflex. In both types of contractile reflexes, intravenous administration of hexamethonium inhibited the reflex contractile activity virtually completely, intravenous atropine inhibited over 90% of the induced contractile activity, thus suggesting that these contractions were mediated reflexly through cholinergic stimulation. These two models of reflex bladder contractions should be useful for the study of hyperreflexic bladders.     

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.     

Use of glycopeptidolipid core antigen for serodiagnosis of mycobacterium avium complex pulmonary disease in immunocompetent patients

We report the development of a serodiagnostic method for Mycobacterium avium complex (MAC) disease with an enzyme immunoassay (EIA) with the MAC-specific glycopeptidolipid (GPL) core as the antigen. In this study, we confirmed by EIA that the GPL core antibody was in the sera of immunocompetent patients with MAC disease. The EIA for quantifying the GPL core antibody was evaluated as a clinical tool for serodiagnosis of pulmonary MAC disease. A significant increase in GPL core antibodies (immunoglobulins G, A, and M) was detected in sera of patients with MAC pulmonary diseases when they were compared to patients who were colonized with MAC, patients with Mycobacterium kansasii disease or tuberculosis, and healthy subjects. The sensitivities and specificities of the GPL core-based EIA for diagnosis of MAC pulmonary disease were 72.6% and 92.2%, respectively, for IgG, 92.5% and 95.1%, respectively, for IgA, and 78.3% and 91.0%, respectively, for IgM. The best sensitivity and specificity were obtained by measuring immunoglobulin A antibodies against GPL core antigen. The level of GPL core antibodies reflected disease activity, since it decreased in cured MAC patients who had responded to chemotherapy. Measurement of serum antibodies against GPL core is useful for both diagnosis and assessment of disease activity in MAC disease of the lung.     

Appearance of prolactin-releasing peptide-producing neurons in the area postrema of adrenalectomized rats

Prolactin-releasing peptide (PrRP) was found to be a novel hypothalamic peptide that stimulates prolactin release in vitro and in vivo. In the normal adult rat brain, PrRP neurons are known to be located in only three areas, i.e. the dorsomedial hypothalamic nucleus, ventrolateral reticular formation; and nucleus of the tractus solitarius in the medulla oblongata. These PrRP neurons project neurites into various brain areas, including regions such as the paraventricular nucleus, supraoptic nucleus, and bed nucleus of the stria terminalis. Both PrRP nerve fibers and a high level of PrRP receptor, UHR-1, mRNA are observed in the area postrema (AP),but no PrRP neurons are detected in the AP of normal rats. In this study, we clearly demonstrated that PrRP-producing cells newly appeared in the AP of adrenalectomized rats by in situ hybridization and immunocytochemistry. Our results suggest that PrRP may have some important roles in the AP of adrenalectomized rats. This is the first report demonstrating the appearance of PrRP-positive cells in the AP.     

Monoclonality of infiltrating plasma cells in primary pulmonary nodular amyloidosis: detection with polymerase chain reaction

AIMS: To investigate the relation between localised amyloidosis and immunocytic dyscrasia. METHODS: Open lung biopsy specimens from a 72 year old man with multiple nodules in the right middle and lower lung were stained with haematoxylin-eosin, Congo red, and antibodies against IgG, IgA, IgM, and kappa and lambda light chains. Semi-nested PCR amplification for the immunoglobulin heavy chain (IgH) gene was performed using consensus primers for the VDJ region of the IgH gene, FR3A, LJH, and VLJH. RESULTS: The biopsy specimens contained eosinophilic amorphous material stained with Congro red and anti-kappa light chain, and surrounded by inflammatory cells intermingled with plasma cells. Plasma cells in the adjacent amorphous material showed cytoplasmic staining with anti-kappa. Polymerase chain reaction revealed a discrete amplified band of apparently uniform size with background smear. CONCLUSIONS: Primary AL type localised amyloidosis involves local accumulation of monoclonal plasma cells and their secreted products, as in nodular cutaneous amyloidosis. Localised AL type nodular amyloidosis is a separate entity in amyloidosis.