Mitogenicity and down-regulation of high-affinity interleukin 2 receptor by YTA-1 and YTA-2, monoclonal antibodies that recognize 75-kDa molecules on human large granular lymphocytes.

A large number of interleukin 2 receptors lacking the Tac epitope (IL-2R/p75) were found to be constitutively expressed on the human large granular lymphocyte/natural killer cell line YT, which bears inducible IL-2R/p55 associated with Tac antigen. Two anti-YT IgG1 monoclonal antibodies, YTA-1 and YTA-2, recognizing different epitopes of the same 75- to 80-kDa molecule, were established. The 75-kDa antigen recognized by these monoclonal antibodies was strongly expressed on the large granular lymphocytes of normal peripheral blood mononuclear cells and on various lymphoid cell lines bearing IL-2R/p75. The YTA-1 and YTA-2 antibodies were mitogenic and were different from other mitogenic monoclonal antibodies such as anti-T3 (CD3), anti-T11 (CD2), and KOLT-2 (CD28). Further, they down-regulated the high-affinity IL-2R of peripheral blood mononuclear cells within 24 hr in culture. The relationship between the YTA-1/2 antigen and the IL-2R system is discussed.     

A primigravida with very‐long‐chain acyl‐CoA dehydrogenase deficiency

Introduction: Valosin‐containing protein (VCP) is a ubiquitously expressed, multifunctional AAA‐ATPase protein. Its dominant mutations cause hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD) or amyotrophic lateral sclerosis. The pattern of muscle weakness in IBMPFD patients is variable and includes limb‐girdle, scapuloperoneal, distal, or axial distributions. Case Report: We report a 63‐year‐old man with progressive scapuloperoneal weakness, head drop, and hyperCKemia since age 40 years. Electromyography showed myopathic changes and rare myotonic discharges. Muscle biopsy revealed numerous lobulated fibers, few fibers with glycogen accumulation, and rare fibers with polyglucosan bodies. Rimmed vacuoles and congophilic inclusions, often seen in IBMPFD, were absent. VCP sequencing identified a novel heterozygous c. 1160G>A mutation resulting in p.Asn387Ser substitution. Conclusions: Our patient broadens the pathological spectrum of VCP‐myopathy and emphasizes the importance of VCP analysis in patients with scapuloperoneal muscular dystrophy despite the absence of Paget disease, dementia, rimmed vacuoles, or intracellular amyloid deposition. Muscle Nerve 50:295–299, 2014     

Serum Alkaline Phosphatase in Cryptogenic Stroke Cases with Active Cancer

Objective We assessed the relationship between the levels of serum alkaline phosphatase, which is often increased with biliary obstruction and bone metastasis, and active cancer in patients with cryptogenic stroke. Methods Serum alkaline phosphatase levels in patients with cryptogenic stroke sampled upon admission were measured using the Japan Society of Clinical Chemistry method used in Japan. Active cancer was defined as a new diagnosis, treatment, progression, or recurrence within six months before admission or metastatic cancer. Multivariate logistic regression analyses were performed to explore the relationship between serum alkaline phosphatase and active cancer in these patients. Results Among the 249 patients classified as having cryptogenic stroke, 64 had active cancer. Patients with cryptogenic stroke with active cancer had significantly higher serum alkaline phosphatase levels (486±497 vs. 259±88.2 U/L; p<0.001) than those without cancer. Multivariate logistic analysis revealed that serum alkaline phosphatase levels ≥286 U/L were associated with cryptogenic stroke with active cancer [odds ratio (OR), 2.669, 95% confidence interval (CI), 1.291-5.517; p=0.008] independent of age ≤70 years old (OR, 3.303, 95% CI, 1.569-6.994; p=0.002), male sex (OR, 0.806, 95% CI, 0.380-1.710; p=0.573), and serum D-dimer levels ≥2.6 μg/mL (OR, 18.78, 95% CI, 8.130-43.40; p<0.001). Conclusion In patients with cryptogenic stroke, high serum alkaline phosphatase levels may be related to active cancer.     

A patient with infantile spasms and low homovanillic acid levels in cerebrospinal fluid: l-dopa dependent seizures?

We report a 3-month-old female with infantile spasms that responded transiently to pyridoxine and permanently to oral l-dopa. Initial CSF levels of homovanillic acid were low, suggesting disturbed turnover of dopamine. These findings suggest that disturbed brain monoamine metabolism may be causally related to infantile spasms.Abbreviations CSF cerebrospinal fluid - HVA homovanillic acid - 5-HIAA 5-hydroxyindoleacetic acid This report is dedicated to Professor Yukio Fukuyama on the occasion of the 20-year anniversary of his chairmanship at the Department of Paediatrics, Tokyo Women's Medical College     

The synergistic antitumor effect of recombinant interleukin-1 and low-dose of cyclophosphamide in tumor-bearing mice

Intraperitoneal (i. p.) treatment of MOPC104E ascitic tumor-bearing BALB/c mice with interleukin-1 (IL-1) followed by a low dose of cyclophosphamide (CPA) resulted in synergistic prolongation of their survival time. This antitumor effect was abolished when administration of CPA preceded that of IL-1. The combined i. p. therapy also eradicated subcutaneous (s. c.) tumors, indicating a systemically operating antitumor mechanism. In Winn assay, splenocytes from MOPC104E-bearing mice treated with the combined therapy completely suppressed the growth of MOPC104E cells, but not that of another syngeneic tumor cell line, RL ♀ -8 cells. This tumor-neutralizing activity was completely abrogated by treatment with anti-asialo-GM1 or anti-Thy 1.2 and complement, and reduced by treatment with anti-Lyt2.2 and complement. Treatment of splenocytes with 1-leucine methyl ester (LeuOMe), which depletes natural killer (NK) cells and macrophages in vitro, did not affect the neutralizing activity. © 1994 Wiley-Liss, Inc.     

A novel antibiotic CJ-17,572 from a fungus, Pezicula sp

A new antibiotic, CJ-17,572 (I) was isolated from the fermentation broth of a fungus Pezicula sp. CL11877. The structure of I was determined to be a new equisetin derivative by spectroscopic analyses. The compound inhibits the growth of multi-drug resistant Staphylococcus aureus and Enterococcusfaecalis with IC50s of 10 and 20 microg/ml, respectively.     

CJ-21,058, a new SecA inhibitor isolated from a fungus

A new equisetin derivative, CJ-21,058 (I) was isolated from the fermentation broth of an unidentified fungus CL47745. It shows antibacterial activity against Gram-positive multi-drug resistant bacteria by inhibiting ATP-dependent translocation of precursor proteins across a bacterial cell membrane.