Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism in schizophrenia is associated with age at onset and symptoms

The substantia nigra pars reticulata (SNR) plays important roles in movement and, in an age- and sex-dependent manner, in seizure control. GABAergic synaptic transmission is critical in both normal development and seizures. In many neuronal types it is excitatory early in development and later switches to the mature hyperpolarizing type. We assessed the time course of the switch of GABAA receptor-mediated postsynaptic currents (PSCs) in anterior SNR neurons of male and female developing rats using the gramicidin perforated patch clamp technique. The switch occurred in males around postnatal day (PN) 17 and in females around PN10. This sex dimorphism may play a role in several other recognized sex differences in the development of SNR and in its regulatory role in seizures.     

Characterization of target genes at the 2p15-16 amplicon in diffuse large B-cell lymphoma

Amplification of 2p has been observed as a recurrent alteration in diffuse large B-cell lymphoma (DLBCL). Whereas two candidate oncogenes, REL and BCL11A, have been investigated as targets for 2p amplification, the question remains as to whether the true target gene in the amplicon is REL, BCL11A or both. We previously identified frequent genomic gains of chromosomal 2p in 25 out of 99 DLBCL cases by means of genome-wide array comparative genomic hybridization (CGH). All of these 25 cases included recurrent copy number gain at 2p15-16. In the study presented here, cases were analyzed in greater detail by means of contig bacterial artificial chromosome (BAC) array CGH for the 4.5-Mb region at 2p15-16, which contained 33 BAC clones. We confined the minimal common region to 500-kb in length, where only the candidate oncogene REL, and not BCL11A, is located. Real-time quantitative PCR was carried out to investigate the correlation between genomic gain and expression. It showed a significant correlation for both genes, indicating that these two genes are common targets for the 2p15-16 amplicon. However, given the fact that REL is more frequently amplified than BCL11A, the REL gene may play a more important role than BCL11A in the pathogenesis of DLBCL.     

A quantitative analysis of lymphatic vessels in human breast cancer, based on LYVE-1 immunoreactivity

This study was undertaken to determine the highly sensitive method for detecting tumour lymphatic vessels in all the fields of each slide (LV), lymphatic microvessel density (LMVD) and lymphatic vessel invasion (LVI) and to compare them with other prognostic parameters using immunohistochemical staining with polyclonal (PCAB) and monoclonal antibodies (MCAB) to the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), and the pan-endothelial marker factor VIII in a series of 67 human breast cancers. In all LYVE-1-stained sections, LV (some of which contained red blood cells) were frequently found localised in extralobular stroma, dermis, connective tissue stroma and adjacent to artery and vein, but were rare within the intralobular stroma or the tumour body (3/67 cases) or areas of widespread invasion. In contrast small blood vessels were observed in intra- and extralobular stroma in the factor VIII-stained sections. Quantitation of vessel numbers revealed that LYVE-1/PCAB detected a significantly larger number of LV than either H&E or LYVE-1/MCAB (P<0.0001). LYVE-1/PCAB detected LVI in 25/67 cases (37.3%) and their presence was significantly associated with both lymph node metastasis (chi(2)=4.698, P=0.0248) and unfavourable overall survival (OS) (P=0.0453), while not relapse- free survival (RFS) (P=0.2948). LMVD had no influence for RFS and OS (P=0.4879, P=0.1463, respectively). Our study demonstrates that immunohistochemistry with LYVE-1/PCAB is a highly sensitive method for detecting tumour LV/LVI in breast cancer and LVI is a useful prognostic indicator for lymphatic tumour dissemination.     

Prediction and treatment of peritoneal dissemination in gastric cancer

In advanced gastric cancer, the frequency of relapses such as metastasis to the peritoneum is high. For this reason, prognostic and treatment methods were studied. In 457 cases in which diagnostic cytology was utilized, 36 (61%) of the 59 cases in which dissemination had been macroscopically observed (P 1) were positive. Moreover, 13 cases of P 0 were also positive. The prognosis of the positive cases was worse, but there was not a significant statistical difference between the positive and negative cases. Chemotherapy has become the most common treatment because of the appearance of new anticancer drugs. TS-1 and paclitaxel were repeatedly administered in 10 cases, and the median survival time was 17 months. These drugs were effective even in carcinoma of the peritoneum, and an improvement in the prognosis can be expected. Surgery was performed in 23 cases due to stenosis of the digestive tract, and in 21 cases the patients were able to eat after surgery. The median postoperative survival time was 7 months, and surgery improved the prognosis. The improved sensitivity of diagnostic cytology and the standardization of chemotherapy and surgery warrant further study.     

Phyllodes tumor of the prostate: a case report

Prostatic phyllodes tumor is an unusual lesion for which there are only occasional reports in the literature. We encountered a phyllodes tumor of the prostate in a 36-year-old man who had complained of urinary frequency and dysuria for one month. In October 1998, he visited our hospital and had a transurethral resection of the prostate (TUR-P) for obstructive symptoms. He experienced recurrent same symptoms in September 1999 and underwent another TUR-P. The pathologic examination at this time revealed phyllodes tumor. In the tumor, despite its regular alternating growth of ducts and stroma, the stromal element appeared histologically malignant, showing marked atypia and rhabdomyosarcoma-like components. Consequently, in December 1999, the patient underwent radical prostatectomy with lymph node dissection. The resection margins and pelvic lymph nodes were free of tumor. The patient remains alive and well after 14 months.     

The methodology of quantitation of microvessel density and prognostic value of neovascularization associated with long‐term survival in Japanese patients with breast cancer

The present study updates results on methodology of quantitation of tumor neovascularization and those on the prognostic value of microvessel density (MVD) in breast cancer tissue previously published in the World J. Surg. 21: 49–56, 1997. The followup period of observation of the series was extended to 20 years, and new biological indicators (i.e., proliferating cell nuclear antigen (PCNA), cerbB2, and p53) were included in the analysis. There were 109 patients with primary breast cancer, from 1971 to 1979, followed up for a median of 14 years (range, 1–20). A representative median longitudinal section of each breast tumor was immunohistochemically stained with factor VIIIrelated antigen and analyzed. The three methods of identifying MVD were: (1) average microvessel count (AMC)/mm2, (2) central microvessel count (CMC)/mm2, and (3) highest microvessel count (HMC)/mm2. Thirtyone patients (28.4%) died of breast cancer. There was a relationship between MVD and peritumor blood vessel invasion (AMC: p = 0.0114, CMC: p = 0.0319, and HMC: p = 0.0009). However, there was no relationship between MVD and other factors. Univariate analysis showed that node status (p < 0.0001), histological grade (p < 0.0001), clinical tumor size (T) (p = 0.0002), PCNA (p = 0.0033), p53 (p = 0.0043), mitotic grade (p = 0.0092), AMC (p = 0.0214), and peritumor lymphatic vessel invasion (p = 0.0467) were significantly predictive of overall survival. HMC was borderline significant (p = 0.0702), while CMC and cerbB2 were not significant. Multivariate analysis showed that T (p = 0.0005), node status (p = 0.0053), and AMC (p = 0.0485) were independent factors, but neither CMC nor HMC was independent. AMC, a significant independent prognostic factor, might be a better method than the others for evaluating angiogenesis, but further and larger studies are warranted.     

Primary marginal zone lymphoma of the thymus accompanied by chromosomal anomaly 46,X,dup(X)(p11p22)

We report a case of primary marginal zone lymphoma in the thymus of a 34-year-old woman. She was initially suspected of having a mediastinal plasmacytoma because of the presence of dominantly proliferating plasmacytic cells in a small fragment obtained by thoracoscopic biopsy, and an elevated level of serum monoclonal IgA. However, histology of the tissue obtained by a subsequent open surgical biopsy revealed diffuse proliferation of atypical monocytoid B-lymphocyte-like cells, which showed prominent plasmacytic differentiation and a close association with thymic epithelial cells consistent with the histology of a marginal zone lymphoma of the thymus. These lymphoma cells were positive for CD19, CD20, IgA, and kappa, and negative for CD5, CD10, and other T/NK-cell and myelomonocyte antigens. Both G-banded and spectral karyotyping analyses revealed the lymphoma cells carried a chromosomal anomaly, 46,X,dup(X)(p11p22). Although large cell type B-cell lymphoma in the thymus (mediastinal diffuse large B-cell lymphoma), which is categorized as a definite subtype in revised European-American classification of lymphoid neoplasms and the new World Health Organization classification, is not infrequent, primary marginal zone lymphoma of the thymus is extremely rare. To our knowledge, this is the first case report of primary marginal zone lymphoma of the thymus with a detailed chromosomal analysis.     

Comparative restriction endonuclease analysis of varicella-zoster virus clinical isolates

The DNAs of 67 isolates of varicella-zoster virus (VZV) obtained from 31 individuals were compared by restriction endonuclease analysis using BamHI, EcoRI, PstI and SmaI. All of the epidemiologically unrelated 26 isolates could be differentiated using SmaI and another one or two enzymes. However, the DNA cleavage profiles of multiple VZV isolates from the same patient and the isolates from a group of patients who were infected with VZV from the same source were found to be identical to each other, as reported previously. No patients were found who were simultaneously infected with different VZV strains. Moreover, VZV showed no change in DNA fragment profiles after serial passages not only through human embryonic lung cells but also through patients.