11q trisomy detected by fluorescence in situ hybridization

Takano T, Yamanouchi Y, Kawashima S, Date M, Hashira S, Kida M, Abe T, Nakahori Y, Nakagome Y. 11q trisomy detected by fluorescence in situ hybridization. Clin Genet 1993: 44: 324–328. © Munksgaard, 1993 A patient with psychomotor developmental delay, multiple minor anomalies, congenital heart disease and left inguinal hernia is reported. His karyotype was 45,X/46,X,+mar (3 : 37 cells), and the marker chromosome was identified as t(Y;11) (q12;q14?) using fluorescence in situ hybridization and fluorescent chromosome painting. He was diagnosed as mosaic for de novo 11q trisomy.     

Expression of the CD28 costimulatory molecule on subsets of murine intestinal intraepithelial lymphocytes correlates with lineage and responsiveness

The CD28 antigen has been recently demonstrated to be a costimulatory molecule and is expressed by almost all thymic and peripheral T cell receptor (TcR) α^δ+ and γ^λ+ cells in the mouse system. We show here that expression of CD28 is heterogeneous among murine intestinal intraepithelial lymphocytes (IEL). Whereas some TcR αβ-expressing IEL subsets such as CD4⁺8^? and CD4^?8α⁺β⁺ cells express CD28 at the same levels as their phenotypic counterparts in lymph node, other subsets of TcR αβ cells (including CD4^?8α⁺β^? and CD4⁺8αβ⁺β cells) as well as TcR γ^λ+ IEL fail to express CD28. Parallel experiments using aged BALB/c-nu/nu mice indicated that CD28 expression patterns among IEL are quite similar to those of normal BALB/c mice. Furthermore, forward light scatter analysis showed that CD28^? cells are considerably larger than CD28⁺ cells in the gut, although cycling cells were rare in both subsets. Finally CD28^? cells in the gut did not proliferate or produce IL-2 upon stimulation by anti-CD3 monoclonal antibodies (mAb) and phorbol 12-myristate 13-acetate, whereas CD28⁺ cells in the gut and lymph nodes responded to these stimuli. The response of the CD28⁺ cells was enhanced by anti-CD28 mAb. These results suggest that CD28^? IEL (CD4-8α⁺β^? cells, and some CD4⁺8α⁺β^?cells) may follow a different developmental pathway from that of CD28⁺ IEL in a thymus-independent environment, and that expression of CD28 correlates with responsiveness of the cells to triggering via the TcR-CD3 complex.     

A possible role of two hydrophobic amino acids in antigen recognition by synovial T cells in rheumatoid arthritis

Synovial T cells play a crucial role in the pathogenesis of rheumatoid arthritis (RA) synovitis. We have quantitatively analyzed the T cell receptor (TcR) variable (V) region gene repertoire of freshly isolated synovial fluid (SF) T cells, comparing it with that of peripheral blood (PB) T cells in RA. The TcR V gene repertoire of PB and SF T cells in RA and osteoarthritis was heterogeneous. In contrast, Vail in SF was expressed to a greater degree in three of five RA patients, and increased levels of Vp6, 1-3 were found in the SF of four of six RA, compared with paired PB. Of note, Vβ6, 1–3 was universally used in four RA patients with a disease duration of less than 10 years, irrespective of their HLA-DR types. This was in contrast to two other RA patients, suffering for more than 20 years, who showed different Vα and Vβ usages. β-chain sequence analysis in RA patients with a preference for Vβ6, 1–3 has shown that a few clones dominated in SF, whereas polyclonality was observed in PB. These findings suggest oligoclonal expansion of T cells in response to specific antigen(s) in the SF of these patients with RA of relatively short duration. Concomitant use of two hydrophobic amino acids, leucine and valine, in the Dβ region was noticeable among the predominant SF clones. These two amino acids might directly contact a peptide specific for the induction of synovitis in RA patients. TcR-directed therapy may, therefore, be useful for the treatment of early RA synovitis.     

No evidence of PEG1/MEST gene mutations in Silver‐Russell syndrome patients

Silver‐Russell syndrome (SRS) is characterized by prenatal and postnatal growth retardation with morphologic anomalies. Maternal uniparental disomy 7 has been reported in some SRS patients. PEG1/MEST is an imprinted gene on chromosome 7q32 that is expressed only from the paternal allele and is a candidate gene for SRS. To clarify its biological function and role in SRS, we screened PEG1/MEST abnormalities in 15 SRS patients from various standpoints. In the lymphocytes of SRS patients, no aberrant expression patterns of two splice variants (α and β) of PEG1/MEST were detected when they were compared with normal samples. Direct sequence analysis failed to detect any mutations in the PEG1/MEST α coding region, and there were no significant mutations in the 5′‐flanking upstream region containing the predicted promoter and the highly conserved human/mouse genomic region. Differential methylation patterns of the CpG island for PEG1/MEST α were normally maintained and resulted in the same pattern as in the normal control, suggesting that there was no loss of imprinting. These findings suggest that PEG1/MEST can be excluded as a major determinant of SRS. © 2001 Wiley‐Liss, Inc.     

The significance of the determination of AFP-isoform in the early diagnosis of hepatocellular carcinoma]

To evaluate the significance of the determination of the AFP-isoform in the early diagnosis of hepatocellular carcinoma (HCC), the AFP-isoform was determined in 48 patients with HCC and in 53 patients with liver cirrhosis, using the lectin electrophoresis of AFP by antibody-affinity blotting technique. 1. The HCC-type AFP-isoform was detected in 44 of the 48 patients with HCC, 2. In about 30% of the patients with HCC, the HCC-type AFP-isoform appeared 3-10 months before the graphic diagnosis of HCC, 3. In about 60% of the patients with liver cirrhosis found to have the HCC-type AFP-isoform, HCC developed within one year. Thus, the serial determination of the AFP-isoform in patients with liver cirrhosis was considered very useful for the early diagnosis of HCC.     

Synthesis of poly(vinyl alcohol) having a thiol group at one end and new block copolymers containing poly(vinyl alchohol) as one constitent

Poly(vinyl alcohol) (PVA) and poly(vinyl acetate) having a thiol group at one end were synthesized by free-radical polymerization of vinyl acetate in presence of thioacetic acid as a chain transfer agent followed by treating with sodium hydroxide/methanol and ammonia, respectively. It was found that block copolymers containing the PVA sequence as one constituent were obtained by the redox-initiated polymerization of some vinyl monomers, for example, acrylic acid (AA) and acrylamide (AAm), using PVA having a thiol end group as reductant and an oxidant such as potassium bromate and potassium persulfate.     

Prognostic significance of the Ki67 index and programmed death-ligand 1 expression after radical cystectomy in patients with muscle-invasive bladder cancer

ObjectivesTo investigate the association between Ki67 index and programmed death-ligand 1 (PD-L1) expression in muscle-invasive bladder cancer (MIBC) patients after RC.Materials and MethodsWe retrospectively evaluated 262 MIBC patients treated with RC between April 2004 and April 2020. The impact of Ki67 index and PD-L1 expression on prognosis was evaluated by univariate Cox regression analysis. In addition, a pathomolecular risk score, including Ki67 and PD-L1, was developed to predict prognosis and pathological factors. We also evaluated the link between the Ki67 index and PD-L1 under the IL-6 stimulation in the bladder cancer cell lines of T24 and 5637 cells.ResultsThe median age and follow-up period was 69 years and 52 months, respectively. Ki67 index and PD-L1 expression were significantly associated with tumor recurrence. Univariate Cox regression analysis showed that pT3–4, mixed histology, lymphovascular invasion positive (LVI+), pN+, Ki67-high (>17%), and PD-L1+ were significantly associated with recurrence-free survival (RFS). The pathomolecular risk score was developed using resection margin+ (1 point), mixed histology (1 point), LVI+ (1 point), pN+ (1 point), and Ki67-high (1 point). RFS and overall survival were significantly shorter in patients with higher pathomolecular risk scores (>1) than in those with lower risk scores (≤1). Cell proliferation was significantly increased in the T24 and 5637 cells under the IL-6 stimulation, while PD-L1 expression was not.ConclusionsA significant effect of Ki67-high and PD-L1 expression on poor prognosis was observed in patients with MIBC. Further studies are necessary to elucidate the precise mechanisms of cell proliferation and PD-L1 expression in patients with MIBC.     

Non-invasive fibrosis assessments of non-alcoholic fatty liver disease associated with low estimated glomerular filtration rate among CKD patients: the Fukuoka Kidney disease Registry Study

Clinical and Experimental Nephrology - A growing body of evidence has shown that non-alcoholic fatty liver disease (NAFLD) is associated with chronic kidney disease (CKD). Non-invasive fibrosis...