Kanazawa Medical University

About: Kanazawa Medical University is a education organization based out in Kanazawa, Japan. It is known for research contribution in the topics: Population & Cancer. The organization has 3103 authors who have published 6322 publications receiving 144592 citations. The organization is also known as: Kanazawa ika daigaku.

Development of the meniscus of the knee joint in human fetuses.

Abstract: Discoid meniscus of the knee joint occurs at a higher incidence in the lateral than in the medial menisci. Although its developmental origin has been suggested, it remains unclear. To verify the developmental etiology, we examined the meniscus of the knee joint in 41 human fetuses (from 14 to 30 weeks of gestation) and 14 adults (from 56 to 91 years of age) comparatively. The articular surfaces of the tibia and meniscus of the left knees in 40 fetuses and 14 adults were photographed and each area was measured by Scion Image (Scion; http://www.scioncorp.com). Morphometric analyses revealed that the proportion of the area of meniscus to that of the plateau was continuously higher in the lateral side than in the medial side. The right knee joints of seven fetuses were histologically observed, and the layered structure of fibers developed earlier in the lateral meniscus than in the medial in fetuses. The observed differential development of lateral and medial sides of the meniscus may be involved in the etiology of discoid meniscus.

Mismatch negativity and p3a/reorienting complex in subjects with schizophrenia or at-risk mental state

Abstract: Introduction: Shorter duration of untreated psychosis has been associated with better prognosis in patients with schizophrenia. In Introduction: In this study, we measured duration mismatch negativity (dMMN), P3a and reorienting negativity (RON) in subjects with at-risk mental state (ARMS), patients with first-episode or chronic schizophrenia, and healthy volunteers. The main interest was to determine if these event-related potentials provide a biomarker associated with progression to overt schizophrenia in ARMS subjects. Methods: Seventeen ARMS subjects meeting the criteria of the Comprehensive Assessment of At-Risk Mental State, 38 patients with schizophrenia (19 first-episode and 19 chronic), and 19 healthy controls participated in the study. dMMN, P3a and RON were measured with an auditory odd-ball paradigm at baseline. Results: During the follow-up period (2.2 years), 4 out of the 19 ARMS subjects transitioned to schizophrenia (Converters) while 15 did not (non-Converters). dMMN amplitudes of Converters were significantly smaller than those of non-Converters at frontal and central electrodes before onset of illness. dMMN amplitudes of non-Converters did not differ from those of healthy controls, while Converters showed significantly smaller dMMN amplitudes compared to control subjects. RON amplitudes were also reduced at frontal and central electrodes in subjects with schizophrenia, but not ARMS. Converter subjects tended to show smaller RON amplitudes compared to non-Converters. Conclusions: Our data confirm that diminished dMMN amplitudes provide a biomarker which is present before and after the development of psychosis. In this respect, RON amplitudes may also be useful, as suggested for the first time in this study.

Molecular characterization of the genomic breakpoint junction in a t(11;22) translocation in Ewing sarcoma.

Abstract: Polymerase chain reaction (PCR)-based nucleotide sequence analysis was performed in 12 cases of Ewing sarcoma on the cDNA and/or genomic DNA breakpoint regions of a t(11;22)(q24;q12), which joins the EWS gene located on chromosome 22 with the FLI1 gene located on chromosome 11, in order to understand the molecular mechanism of this translocation. Reverse transcriptase-PCR on total tumor cell RNA from the examined cases showed five types of EWS-FLI1 chimeric product, resulting from various junctions between EWS exon 7 or 10 with FLI1 exon 5, 6, or 8. Sequencing of the genomic fusion junctions of EWS-FLI1 in seven cases showing three types of the chimeric cDNA products revealed that most of the breakpoint junctions shared common nucleotide(s) from both genes, and that the breakpoints in EWS introns 7 and 10 clustered within 100 bp and 300 bp, respectively. All the junctions were found to be flanked by various oligomers, among which a consensus sequence, 5'-AGAAAARDRR-3', was found near the breakpoints of both genes in four cases, suggesting that these oligomers may have a functional significance in the genesis of t(11;22). In addition to these oligomers, sequences highly homologous to Alu repeats and/or eukaryotic topoisomerase II cleavage sites were located near, or flanked, or even encompassed, the breakpoints in most of the cases examined. Thus, these sequences may also mediate DNA double-strand breakage and rejoining to generate the t(11;22). Genomic sequence analysis of both EWS-FLI1 and FLI1-EWS chimeric genes in three of the seven cases demonstrated a deletion and duplication of both EWS and FLI1 sequences in two cases and no gain or loss in one case. The present findings suggest that multiple mechanisms may be operative for the break and rejoining of the fragments of chromosomes 11 and 22 in the genesis of t(11;22), and that some of these translocations are asymmetric at the molecular level.

PARP6, a mono(ADP-ribosyl) transferase and a negative regulator of cell proliferation, is involved in colorectal cancer development.

Abstract: Poly(ADP-ribose) polymerase (PARP) is an enzyme that mediates post-translational modification of proteins. Seventeen known members of the PARP superfamily can be grouped into three classes based on catalytic activity: (i) classical poly(ADP-ribose) polymerases, (ii) mono(ADP‑ribosyl) transferases and (iii) catalytically inactive members. PARP6 belongs to the mono(ADP-ribosyl) transferase class, and here we have found that PARP6 is a negative regulator of cell proliferation. Forced expression of PARP6 in HeLa cells induced growth suppression, but a PARP6 mutant with a C-terminal deletion lacking the catalytic domain had no effect. The PARP6-expressing cells accumulated in the S-phase, and the magnitude of S-phase accumulation was observed to be greater in cells expressing a PARP6 mutant with an N-terminal deletion, lacking a putative regulatory domain. Immunohistochemical analysis revealed that PARP6 positivity was found at higher frequencies in colorectal cancer tissues with well-differentiated histology compared to those with poorly differentiated histology. Furthermore, PARP6 positivity negatively correlated with the Ki-67 proliferation index. Kaplan-Meier analysis showed that PARP6-positive colorectal cancer had a good prognosis. Based on these results, we propose that PARP6 acts as a tumor suppressor through its role in cell cycle control.