Reduction of carotid artery blood flow in pediatric patients with syncope: evaluation with head-up tilt test

We investigated the effect of postural changes on cerebral circulation by measuring carotid artery blood flow (CABF) in the supine position and during head-up tilt (HUT) test using a Doppler flow meter. Subjects included 10 patients with neurally mediated syncope, 10 patients with orthostatic intolerance, 8 with epilepsy, aged between 8 to 24 years (mean +/- SD, 13.9 +/- 4.1 years). The test caused pallor and dizziness in 16 patients (symptomatic), while no symptoms were recognized in the other 12 patients (asymptomatic). Significant reductions in the mean CABF (Fm), maximum CABF (Fs) and minimum CABF (Fd), components of the CABF waveform, were noticed during HUT compared to before HUT (supine), and these reductions in symptomatic patients were more severe than those in asymptomatic patients (Fm: - 2.8 +/- 2.0 SD vs - 0.7 +/- 1.4 SD; Fs: - 2.7 +/- 1.5 SD vs - 0.9 +/- 1.3 SD; Fd: - 4.5 +/- 2.8 SD vs - 2.2 +/- 2.1 SD). Reductions in Fm, Fs and Fd in the symptomatic patients during HUT lasted longer than those of the asymptomatic patients, being statistically significant for Fm and Fs (Fm: p < 0.01; Fs: p < 0.05). The criteria during HUT for distinguishing neurally mediated syncope (NMS) from others was Fs: < - 4 SD and Fd: < - 5 SD. Our data suggest that reduction of CABF should be carefully evaluated for the diagnosis of neurally mediated syncope in pediatric patients. Such a reduction might be an essential mechanism of syncopal attacks.     

Mechanism of Accumulation of the Antitumor Protein Antibiotic Neocarzinostatin in Bladder Tissue: Intravenous Administration, Urinary Excretion, and Absorption into Bladder Tissue

Some aspects of the absorption, distribution, and excretion of neocarzinostatin (NCS), a proteinous antitumor antibiotic, were studied in rabbits. NCS was given intravenously (i.v.) via the auricular vein, or [(14)C]NCS was instilled directly into the cavity of the bladder by tubing. In both groups, ureterostomy was performed, so that the drug excreted in the urine did not pass through the bladder. The results showed extremely rapid renal clearance; namely, two-thirds of the total recovered was excreted in the first 5 min. It was also shown that drug infused into the bladder cavity could be recovered in urine from the ureterostomized ureter. Also, the level of biological activity of NCS in bladder tissues after i.v. administration is significantly lower when ureterostomy is performed. Thus, evidence is presented for the absorption of NCS into bladder tissue from the lumen of the bladder. The high levels of NCS in bladder tissue are due to this effect as well as to accumulation via the iliac artery. These data should encourage further trials of NCS in bladder cancer. A study of urine containing NCS derived from i.v. administration showed an increase in antibacterial activity upon incubation, followed by a decrease. These effects are probably due to proteolysis, as shown by the appearance of a low-molecular-weight fragment and by the absence of such an increase in the presence of inhibitors of proteolysis.     

Clinicopathologic significance in serum presence of anti-p53 antibody in patients with colorectal carcinoma

BACKGROUND/AIMS: Alteration of p53 gene links to the appearance and detection of anti-p53 antibodies in the serum. The aim of this study is to find the clinicopathologic significance for serum presence of anti-p53 antibodies in patients with colorectal carcinoma. METHODOLOGY: Serum presence of anti-p53 antibodies was examined for sera of 36 patients with colorectal carcinoma using enzyme-linked immunosorbent assay. RESULTS: Frequency of serum presence of anti-p53 antibodies was 47.2% (17 of 36). Incidence of lymph node metastasis and lymphatic invasion in tumors coexisting with serum presence of anti-p53 antibodies (70.6%, 12 of 17 and 94.1%, 16 of 17) were significantly higher than those in tumors without serum presence of anti-p53 antibodies (17.6%, 3 of 17 and 68.4%, 13 of 19; p = 0.007 and p = 0.041, respectively). Stages of the tumors were significantly more advanced in carcinomas coexisting with serum presence of anti-p53 antibodies (p = 0.023). Frequency in serum presence of anti-p53 antibodies among patients with tumors expressing p53 (73.7%, 14 of 19) was significantly higher than that among patients with tumors without p53 expression (17.6%, 3 of 17; p = 0.0005). CONCLUSIONS: Preoperative serum appearance of anti-53 antibodies can be an indicator for more malignant potential of colorectal carcinoma.     

Identification of HLA-A*2402-restricted epitope peptide derived from ERas oncogene expressed in human scirrhous gastric cancer

ERas is a recently identified oncogene involved in the tumorgenic growth of embryonic stem cells. We examined the significance of ERas expression in scirrhous gastric carcinoma, and the possibility of ERas as a tumor-associated antigen of gastric cancer for developing a cancer vaccine. ERas expression was determined in scirrhous gastric carcinoma specimens by immunohistochemical staining. To assess the possibility of the ERas protein as an anticancer vaccine target, we examined whether ERas for HLA-A-restricted epitope peptides were capable of eliciting cytotoxic T lymphocyte activity. Immunohistochemical analysis identified ERas protein in the nucleus and cytoplasm of cancer cells, yet ERas was not expressed in normal gastric epithelium. By western blotting, lysates of the scirrhous gastric cancer cell lines, OCUM-8, OCUM-2MD3 and OCUM-2M were shown to contain a 25-kDa band of ERas protein. ERas mRNA was detected in these cell lines by RT-PCR. To investigate cytotoxicity, we successfully established cytotoxic T lymphocyte clones stimulated by HLA-A*2402-restricted ERas peptides (FALDDPSSL). These peptides have specific cytotoxicity against corresponding HLA-A*2402-positive target cells pulsed with the candidate peptide. We found that the cytotoxic T lymphocyte clones demonstrated cytotoxic activity against OCUM-8 cells that endogenously express ERas. Our results suggest that ERas is a novel tumor-associated antigen with the potential application to be a vaccine against scirrhous gastric cancer.     

Tumor-associated MUC5AC stimulates in vivo tumorigenicity of human pancreatic cancer

MUC5AC, a high molecular weight glycoprotein, is overexpressed in the ductal region of human pancreatic cancer but is not detectable in the normal pancreas, suggesting its association with disease development. In the present study, we investigated the in vitro and in vivo effects of MUC5AC knockdown by short interfering RNA (siRNA) in the MUC5AC-overexpressing SW1990 and BxPC3 human pancreatic cancer cell lines in order to clarify its function. Significant decreases in the expression levels of MUC5AC mRNA and protein were observed in SW1990 and BxPC3 cells that had been stably transfected with a MUC5AC siRNA expression vector (SW1990/si-MUC5AC and BxPC3/si-MUC5AC cells) compared to those in cells transfected with an si-mock vector (SW1990/si-mock and BxPC3/si-mock cells). In in vitro studies, neither type of MUC5AC-knockdown cell showed any difference in cell survival, proliferation, or morphology from the si-mock cells or parental cells. However, in vivo xenograft studies demonstrated that MUC5AC knockdown significantly reduced the tumorigenicity and suppressed the tumor growth of si-MUC5AC cells compared to those of the si-mock cells. Immunohistochemical analysis revealed that CD45R/B220+ and Gr-1+ cells had infiltrated into the tumor tissue of the SW1990/si-MUC5AC cells. Furthermore, cancer-associated antigen specific antibodies were detected at high levels in the sera from the SW1990/si-MUC5AC cell-bearing mice. These results suggest that tumor-associated MUC5AC expressed on the surface of pancreatic cancer cells supports the escape of pancreatic cancer cells from immunosurveillance. The present findings highlight a new dimension of MUC5AC as a functional immunosuppressive agent and its important role in pancreatic cancer progression.     

The complex of immunoglobulin A and uromodulin as a diagnostic marker for immunoglobulin A nephropathy

Background

The only tool to diagnose immunoglobulinn A nephropathy (IgAN) is renal biopsy which requires hospitalization; moreover, renal biopsy has a risk of critical bleeding. Therefore, a non-invasive method for accurate diagnosis of IgAN is desirable and a must-to-have tool for the clinics. For this purpose, we evaluated the diagnostic value of the IgA–uromodulin complex in the urine of patients with IgAN for its feasibility and adequacy.

Method

We determined the IgA–uromodulin complex as a candidate for a diagnostic marker of IgAN by immunoprecipitation, liquid chromatography?mass spectrometry (LC–MS) and Western blot analysis. The enzyme-linked immunosorbent assay (ELISA) for the IgA–uromodulin complex was developed and applied to urine samples obtained from various kidney disease patients.

Result

One hundred and three of 126 urine samples (81.7%) from IgAN patients were positive for the IgA–uromodulin complex, while only 25 out of 94 urine samples (26.6%) in other kidney disease patients were positive. Sensitivity was 81.7%, specificity was 73.4%, and diagnosis efficiency was 78.2%. The complex was negative in eight urine samples obtained from patients with Alport syndrome which is almost impossible to discriminate from IgAN by routine urinalysis.

Conclusion

Detection of the urinary IgA–uromodulin complex by ELISA is a useful non-invasive method to diagnose IgAN.     

An adapter for stapling of a colorectal anastomosis

A technique involving the use of an end-to-end anastomosing stapler for low anterior resection has been modified to allow for a low colorectal anastomosis with an anus-pushing rubber adapter. The facility and safety of this procedure, under direct vision, has been confirmed.     

Minute gastric carcinoid tumor with regional lymph node metastasis

A minute carcinoid tumor of the stomach developed into a regional metastasis around the celiac axis. There was marked lymphangitic and venous invasion of the tumor cell cluster around the tumor, in the submucosal layer. We wish to emphasize that radical gastrectomy with extended lymphadenectomy should be performed, even for a minute carcinoid tumor, as there will probably be a lymph vessel-related metastasis.     

Scanning electron microscopic observations of the vascular structure of vertebral end-plates in rabbits

We used scanning electron microscopy to examine the microcirculation in the vertebral end-plates of rabbits. The arteriola arborizes and swells at the end-plate and then coils to make a microvessel loop. This loop is the structure we refer to as a vascular bud. We suggest that these loop structures of the capillaries play a major role in the nutrition of the intervertebral discs.     

Helicobacter pylori infection in gastric xanthomas: lmmunohistochemical analysis of 145 lesions

A total of 145 paraffin-embedded biopsy samples of gastric xanthoma were analyzed for the localization of Hellcobacter pylorl (HP) antigens. By the indirect immunoperoxidase method using a polyclonal antibody, HP lnfection was identffied on the surface of foveolar cells In 69 (48%) samples. In 38 (55%) of the 69 lesions, the HP antigens were demonstrated in the cytoplasm of xanthoma cells clustered in the actively inflamed lamina propria mucosae, Among the remalning 76 xanthoma lesions negative for HP lnfection on the epithellal surface, only eight (11%) showed the existence of HP antigens in the foamy histiacytes, and 39 (51 %) revealed mild inflammatory change. Monoclonal antibody study using 75 specimens also gave a comparable result. Pre-embedding lmmunoelectron microscopy using paraffin sections revealed positively labeled rod-shaped bacteria both on the epithelial surface and in the phagosome of the xanthoma cells. These findings strongly suggest that some of the xanthoma lesions are provoked by lamina proprial invasion of surface-infected HP.