T cell can recognize the allospecificities formed by the substitution of amino acids associated with HLA-Bw4/Bw6 public epitopes.

Our previous studies clearly showed that HLA-B35 and HLA-Bw53 differed only by the amino acids associated with HLA-Bw4/Bw6 epitopes, in that the former possessed Bw6 and the latter Bw4 epitope. It remains to be known whether T cell can discriminate HLA-B35 from HLA-Bw53, although the difference between these HLA antigens is discriminated by monospecific human alloantisera. To investigate allorecognition of these HLA antigens by T cells, anti-HLA-Bw53 cytotoxic T lymphocytes (CTLs) were generated. Anti-HLA-Bw53 cytotoxic T lymphocytes (CTLs) were generated. Anti-HLA-Bw53 bulk CTLs from an individual with HLA-B35 clearly discriminated HLA-Bw53 from HLA-B35. On the other hand, anti-HLA-Bw53 bulk CTLs from an individual without HLA-B35 revealed weak cross-reactivity with HLA-B35 and HLA-B51. The additional studies using HLA-Bw53 or HLA-B35-specific CTL clones showed that some but not all of the CTL clones definitively distinguish the difference between HLA-Bw53 and HLA-B35. Thus, the allospecificities formed by HLA-Bw4/Bw6 epitopes were discriminated by allogeneic T cells. The present study demonstrated that HLA-Bw4/Bw6 public epitopes play an important role in allorecognition of T cells.     

Matrix metalloproteinase production by COOH-terminal heparin-binding fibronectin fragment in rheumatoid synovial cells

Fibronectin with IIICS region is present in rheumatoid synovium, and fibronectin fragments are increased in rheumatoid joints. We investigated the ability of COOH-terminal heparin-binding fibronectin fragment (COOH-HBFN-f) containing IIICS to induce matrix metalloproteinase (MMP) production and the role of mitogen-activated protein kinase (MAPK) pathway and CS-1 sequence that can bind alpha4beta1 integrin in MMP induction by COOH-HBFN-f in rheumatoid synovial fibroblasts (RSF). When RSF in monolayer culture were incubated with COOH-HBFN-f, COOH-HBFN-f stimulated the production of MMP-1, MMP-3, and MMP-13 by RSF in association with activation of extracellular signal-regulated kinase, p38 MAPK, and c-Jun NH(2)-terminal kinase. Immunoprecipitation of cell lysates demonstrated the presence of alpha4 integrin in cultured RSF. Similar to COOH-HBFN-f, treatment with CS-1 synthetic peptide derived from IIICS resulted in increased MMP production and activation of the kinases, although the MMP levels were low. Preincubation of RSF with anti-alpha4 integrin antibody resulted in partial suppression of the COOH-HBFN-f-stimulated MMP production. Inhibition studies using protein kinase inhibitors (PD98059 and SB203580) showed that those MAPK pathways contributed to MMP up-regulation by COOH-HBFN-f and CS-1. Thus, the present results have clearly shown that COOH-HBFN-f and CS-1 stimulate MMP production in association with activation of MAPK pathways in RSF. Integrin alpha4beta1 may be partially involved in the MMP induction by COOH-HBFN-f.     

Conservation of genes encoding HLA-B5 and B35 cross-reactive group antigens in various races

HLA-B5 and B35 CREG antigens include HLA-B35, B51, B52, B53, and B78. Recent studies suggest that the genes encoding the HLA-B5, B35 CREG, and HLA-B58 antigens share a common ancestor. We sequenced the exons of the genes encoding HLA-B51, B53, and B58 from American black individuals and the gene HLA-B52 encoding from an Arabic individual, and compared them with previously reported sequences of HLA-B51 (B^*5101) and HLA-B52 (B^*5201) from Japanese, HLA-B53 (B^*5301) from an Algerian, and HLA-B58 (B^*5801) from a Sardinian. The sequences of the genes from the American black and Arabic individuals were identical to those from the other races. These findings support the hypothesis that these antigens have evolved prior to divergence of the major ethnic groups.     

Correlation between the number of apoptotic cells and expression of the apoptosis-related antigens Fas, Ley and bcl-2 protein in non-Hodgkin's lymphomas

The relationship between the number of apoptotic cells and the expression of apoptosis-related antigens was examined In 56 cases of non-Hodgkin's lymphomas and in 10 cases of reactive hyperplastic lymph nodes (RHL). Apoptosis was visually quantified by the in situ end-labeling (ISEL) method, and the expression of Fas, Le^y antigens and bcl-2 protein was examined by Immunohistochemistry. The expression of Le^y antigen was observed in germinal centers of RHL and 45% of non-Hodgkin's lymphomas. The apoptotic cell count (AC) in follicular lymphomas was significantly less than that in diffuse lymphomas. The distribution pattern of apoptotic cells In follicular lymphomas was inverse to that in RHL. In follicular lymphomas, AC was lower in follicles than in inter-follicular areas. In contrast, AC was higher in follicles than in Interfollicular areas in RHL. Le^y antigen-positive lymphomas showed a significantly higher AC than the negative cases. The Fas antigen-positive lymphomas showed a higher AC than the negative cases. However, AC in bcl-2 protein-positive and negative cases was not significantly different. These results suggest that Le^y and Fas antigens appear to be involved in the apoptotic tendency of tumor cells in non-Hodgkin's lymphomas, whereas bcl-2 does not necessarily.     

QT interval and QT dispersion in eating disorders

BACKGROUND: Eating disorders are thought to be risk factors for cardiac sudden death secondary to arrhythmia. Results in previous studies on QT interval and QT dispersion, markers of fatal arrhythmia, have been inconsistent. METHODS: We prospectively examined 179 female eating disorder patients, being over 18 years old and diagnosed according to the DSM-IV criteria between January 1995 and December 2002, and 52 healthy women. Patients with abnormal plasma electrolytes or taking medications that might influence the electrocardiogram (ECG) were excluded from the study. QT intervals were corrected for heart rate using Bazett's formula and the nomogram method, which is more reliable at extremely low heart rates than Bazett's formula. QT dispersion was measured as the difference between the longest and shortest QT intervals. QT intervals and QT dispersion in each patient group were compared with those in the control group. RESULTS: The 164 eligible patients consisted of 43 patients with anorexia nervosa restricting type, 35 with anorexia nervosa binge eating/purging type, 63 with bulimia nervosa purging type, and 23 with bulimia nervosa non-purging type. There was no significant difference in age between eating disorder patients and controls. QT interval and QT dispersion were significantly longer in all eating disorder subtypes than in the control group. QT interval and QT dispersion were significantly correlated with the rate of body weight loss in bulimia nervosa. CONCLUSIONS: QT interval and QT dispersion were prolonged in both anorexia nervosa and bulimia nervosa. Examination of ECG in eating disorder patients without extremely low body weight also appears to be clinically important.     

BOVINE SERUM ALBUMIN (BSA) NEPHRITIS IN RATS IV. A SEQUENTIAL EVALUATION OF MONONUCLEAR PHAGOCYTE SYSTEM (MPS) FUNCTION

A clearance kinetic study of intravenously administered ¹²⁵I-labeled aggregated human IgG (¹²⁵I-AHIgG) from the circulation and its distribution in various organs was performed weekly during the course in a model of experimental immune complex glomerulonephritis which was induced in rats immunized 8 weeks previously with 6 times a week administration of 2 mg of bovine serum albumin (BSA) for 4 weeks from week 8 to 12. The removal rates of the injected ¹²⁵I-AHIgG from the circulation were retarded in nonproteinuric rats of week 9 and 10, at almost every checked point (p-value was <0.01). The clearance in those rats with severe proteinuria returned to the level of the control and of rats in week 8. The distribution of ¹²⁵I-AHIgG in the liver 4 hours after the administration revealed a considerable decrease in non-overt proteinuric rats of weeks 9, 10, and 11. A similar tendency of decreasing depositions of the radioactivity was shown in the spleen at each 4 hours. In contrast, the uptakes in the kidney and lung at the final week of 12 were larger. Delayed clearance from the circulation and a decreasing handle of the injected macromolecule in the liver and possibly in the spleen may suggest the presence of some impairment of the MPS function in the course of this experimental glomerulonephritis.     

Multisystem Inflammatory Syndrome in Adults after Mild SARS-CoV-2 Infection,Japan

In Japan, a 51-year-old man had minimally symptomatic severe acute respiratory syndrome coronavirus 2 infection. Multisystem inflammatory syndrome was diagnosed ≈5 weeks later; characteristics included severe inflammation, cardiac dysfunction, and IgG positivity. Clinicians should obtain detailed history and examine IgG levels for cases of inflammatory disease with unexplained cardiac decompensation.     

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.