A cancer-prone case with a background of methylation of p16 tumor suppressor gene.

PURPOSE AND EXPERIMENTAL DESIGN: To date, the presence of p16 gene promoter methylation associated with loss of protein expression has been demonstrated frequently in digestive tract cancers. In this study, we tested for the methylation status of p16 promoter in normal tissue specimens using the methylation-specific PCR technique to examine whether p16 methylation already existed in the background of tumors. RESULTS: Aberrant promoter methylation of p16 gene was detected in 1 of 40 esophageal and 1 of 69 gastric and no colorectal epithelium specimens, and these 2 specimens were derived from the same patient. We also found the same methylation change in both tumor and blood cell DNA. CONCLUSION: These results suggested that the p16 gene was inactivated by methylation in normal background cells of this patient and that other additional factors may promote tumor development in his esophageal and gastric tissues.     

Hypogammaglobulinaemia in a patient with ring chromosome 21

An 8 year old boy with ring chromosome 21 who was susceptible to sinorespiratory infections due to hypogammaglobulinaemia is reported. He presented with the characteristic features of monosomy 21 syndrome, such as psychomotor retardation, hypertonia, large saccular ears, prominent nasal bridge, micrognathia, thrombocytopenia, and patent ductus arteriosus. His serum IgG concentration was less than 1.5 g/l at 3 years and 6 months of age after repeated hospitalisations with pneumonia, otitis media, and convulsions. Regular replacement of intravenous gammaglobulin effectively reduced such infectious episodes. A predisposition to infection in patients with ring chromosome 21 may be explained by hypogammaglobulinaemia and merit treatment with gammaglobulin.

     

Ultrasound in urodynamics

Recent developments of ultrasound imaging have contributed much to the understanding of urodynamics in patients with lower urinary tract symptoms (LUTS). These include ultrasound estimated bladder weight (UEBW), transrectal power Doppler imaging of the prostate and transrectal ultrasonography during voiding (voiding TRUS). UEBW, which is obtained by measuring the thickness of the anterior bladder wall using a 7.5 MHz probe, represents well the degree of bladder hypertrophy caused by obstruction. This parameter is, accordingly, of clinical use in the evaluation of obstruction. The UEBW predicted the presence of obstruction as determined by pressure-flow study with a diagnostic accuracy of 73%. Transrectal power Doppler imaging of the prostate has made it easy to detect prostatic vessels and furthermore to obtain their resistive index (RI). Accumulating data suggest strongly that RI reflects the intraprostatic pressure. More interestingly, RI decreases significantly during voiding in normal subjects but not in patients with benign prostatic hyperplasia. Thus, this method is of particular use in monitoring noninvasively the dynamic change in intraprostatic pressure during voiding. Voiding TRUS makes it possible to monitor the movement of not only the posterior urethra but also the prostate during voiding. Based on our recent study, the anterior fibromuscular stroma (AFMS) seems to contract to open the urethra. Although the physiological function of the AFMS in the prostate remains unknown, AFMS may play a significant role in normal micturition. Due to its noninvasiveness and ease of application, ultrasound imaging would play a vital role in the diagnostic process for patients with LUTS in future.     

Fetal striatal transplants reinstate the electrophysiological response of pallidal neurons to systemic apomorphine challenge in rats with excitotoxic striatal lesions

Previous studies with single-unit recording and 2-[14C]deoxyglucose quantitative autoradiography have shown that systemic administration of apomorphine increases the functional activity of pallidal neurons, and that the enhancement in the globus pallidus (GP) activity is abolished by striatal lesions. The present study employing electrophysiological techniques tested whether embryonic striatal tissue implanted in the excitotoxically damaged striatum of rats may affect the lesion-induced alteration in the neuronal response of GP to apomorphine. Systemically administered apomorphine significantly increased spontaneously firing rates of GP cells. The blockade of dopamine receptors with haloperidol reversed the increased rate to baseline levels. Quinolinate-induced striatal lesions attenuated the rate-increasing effect of apomorphine. Embryonic striatal grafts placed in the lesioned striatum restored the response of GP cells to systemic apomorphine. The graft-mediated restoration of the GP neuron response to apomorphine were accompanied by an improvement in the motor asymmetry induced by this drug. Considering previous anatomical data to demonstrate extensive innervation of the GP by embryonic striatal grafts, the present results suggest that the grafts reconstruct the functional striatopallidal pathway which is capable of transmitting apomorphine-induced changes in the neuronal activity.     

Trastuzumab-mediated antibody-dependent cellular cytotoxicity against esophageal squamous cell carcinoma.

PURPOSE: In the present study, we investigated the degree of protein expression and gene amplification of HER-2 in esophageal squamous cell carcinoma (SCC) cell lines and freshly isolated tumors, and trastuzumab-mediated biological activity, in particular antibody-dependent cellular cytotoxicity (ADCC) against HER-2-expressing esophageal SCC cell lines. EXPERIMENTAL DESIGN: Ten different SCC cell lines with various levels of HER-2 status evaluated by flow cytometry, immunocytochemistry (HercepTest), and fluorescence in situ hybridization were evaluated for ADCC, growth inhibitory, or apoptosis-inducing activities mediated by trastuzumab. RESULTS: Trastuzumab induced ADCC against HER-2-expressing esophageal SCC and the activities reflected the degree of HER-2 expression analyzed by flow cytometric analysis, but not by HercepTest nor fluorescence in situ hybridization analysis. Furthermore, trastuzumab-mediated ADCC against transforming growth factor-beta-producing SCC was enhanced by the treatment with SB-431542, which is a selective inhibitor of the phosphorylation induced by transforming growth factor-beta. There were very marginal effects of anti-proliferative or apoptosis-inducing activities mediated by trastuzumab for HER-2-expressing esophageal SCC. CONCLUSION: HER-2-expressing esophageal SCC cells could be killed by trastuzumab-mediated ADCC and the activity reflected the degree of HER-2 expression detected by flow cytometry.     

Small follicular lymphoma arising near the ampulla of vater

A 49-yr-old Japanese woman underwent upper gastrointestinal endoscopy because of nonspecific dyspepsia. Endoscopy revealed a flat elevated lesion about 15 mm in diameter adjacent to the duodenal papilla, the surface of which was uneven and covered with whitish granules. Based on the results of histological examination with immunohistochemistry (positive for CD10, CD20, CD79a, and bcl-2 protein, negative for CD5 and cyclin D1), a diagnosis of grade 1/3 follicular lymphoma was established. Systemic staging examinations suggested the lymphoma was restricted to the mucosa and superficial portion of the submucosa in the duodenal wall. The patient was treated with a combination of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and monoclonal anti-CD20 antibody (rituximab), in addition to radiotherapy. After six courses of this combination chemotherapy, complete regression of the lymphoma was observed. Although reports of small duodenal lymphoma (<20 mm or localized to the mucosa or submucosa) are extremely rare, the features of this case are characteristic of small duodenal lymphoma in terms of evolution around the ampulla of Vater, low-grade follicular type, occurrence in a women, occurrence in the fourth decade of life, and favorable outcome, and this type of tumor may need to be distinguished by pathogenesis and clinical behavior from various other gastrointestinal lymphomas.     

Property of thimerosal-induced decrease in cellular content of glutathione in rat thymocytes: a flow cytometric study with 5-chloromethylfluorescein diacetate.

There is a concern on the part of public health community that adverse health consequences by thimerosal, a preservative in vaccines for infants, may occur among infants during immunization schedule. Therefore, the effect of thimerosal on cellular content of glutathione was examined on thymocytes obtained from 4-week-old rats using a flow cytometer and 5-chloromethylfluorescein diacetate. Thimerosal at concentrations ranging from 1 to 10 microM reduced the cellular content of glutathione in a concentration-dependent manner, and the complete depletion of cellular glutathione was observed when the cells were treated with 30 microM thimerosal. L-Cysteine significantly attenuated the actions of thimerosal to reduce the glutathione content and to increase the intracellular Ca2+ concentration. Prolonged incubation (24 h) with 1-3 microM thimerosal induced the apoptosis. The cytotoxic action of thimerosal was greatly augmented when the cells suffered oxidative stress induced by H2O2. It may be unlikely that thimerosal exerts potent cytotoxic action under the in vivo condition because the blood concentration of thimerosal after receiving vaccines does not seem to reach micromolar range and nonprotein thiols at micromolar concentrations are present in the blood.