Apperceptive form visual agnosia caused by anti-TNFalpha therapy to rheumatoid arthritis]

TNFalpha plays an important role as an inflammatory mediator in both several autoimmune diseases and multiple sclerosis. Anti-TNFalpha antibody has been widely used to treat rheumatoid arthritis and Crohn's disease. On the. other hand, anti-TNFalpha antibody treatment increased recurrence rate in clinical trials for multiple sclerosis. We report a patient with rheumatoid arthritis without past history of any neurological disorders, who developed diplopia, ataxia, and visual agnosia specific to line drawing in the course of anti-TNFalpha antibody treatment. MRI studies detected multiple demyelinating lesions in the cerebral white matter and brainstem. The present case indicates that careful observation of neurological symptoms is important in the course of anti-TNFalpha antibody treatment, even in patients without past history of demyelinating diseases.     

Case of ruptured gastroduodenal arterial pseudoaneurysm with penetration to the duodenum, successfully treated with transcatheter arterial embolization]

A 77-year-old man, who underwent segmental pancreatectomy for intraductal papillary mucinous adenoma in 2001, was referred to our hospital with complaints of hematemesis and melena on January, 2004. Emergency upper gastrointestinal endoscopy showed a pulsating submucosal protrusion in the duodenal bulb, which was identified as a gastroduodenal arterial aneurysm measuring 1.5cm on abdominal CT imaging. Transcatheter arterial embolization of the aneurysm with metallic coils was successfully performed. Periodically repeated endoscopic examination has revealed the coils protruding into the duodenal lumen without any serious complication.     

A novel compound heterozygous dysferlin mutation in Miyoshi myopathy siblings responding to dantrolene

Miyoshi myopathy (MM) is an autosomal recessive distal muscular dystrophy characterized by mutations of the dysferlin gene. Although several pairs of homozygous/heterozygous mutations have been reported, few effective treatments of MM are available. We had observed the decreased serum creatine kinase (CK) before and after administration of dantrolene in the elder brother and the increased serum CK before and after discontinuance of the drug on suspicion of drug-induced hepatopathy in the younger sister. We report a novel pair of heterozygous mutations in the 3'-splicing site of exon 26 and the translation site of exon 28 of the dysferlin gene in two siblings, and effective treatment of their MM with dantrolene.     

Solitary right ventricle metastasis by renal cell carcinoma.

A 57-year-old man with a history of renal cell carcinoma presented with presyncope. He underwent nephrectomy years earlier followed by HLA-matched allogeneic peripheral-blood stem-cell transplantation. Echocardiographic investigation revealed a solitary right ventricle mass without contiguous vena caval or right atrial involvement. The mass was pathologically confirmed to be metastatic carcinoma in the right ventricular cavity. This case highlights the need to consider an underlying neoplastic syndrome in patients presenting isolated right ventricle mass by echocardiography.     

Activated caspase expression and apoptosis increase in keloids: cytochrome c release and caspase-9 activation during the apoptosis of keloid fibroblast lines

To characterize apoptosis in keloids and the mechanisms responsible for this process, the expression of activated caspase-9 and -3 in fibroblasts obtained from keloids was analyzed. Immunohistochemistry revealed that the number of fibroblasts positive for terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) or activated caspase-9 or -3 was low but was significantly higher in keloid tissues than in normal scar tissues. Significant relationships between the number of caspase-positive fibroblasts and TUNEL-positive fibroblasts suggested that the activation of caspase-9 and -3 induces apoptosis in a subpopulation of keloid fibroblasts. All keloid fibroblast cell lines established in this study showed activation of caspase-9 and -3 after serum deprivation for 3 or 4 hours, as shown using Western blotting. Furthermore, serum deprivation-induced apoptosis in a keloid fibroblast line was blocked by a caspase-9 inhibitor (acetyl-Leu-Glu-His-Asp-al), indicating that activation of caspase-9 was necessary for the process of apoptosis in keloid fibroblasts. Although serum deprivation did not significantly change the level of apoptosis protease activating factor-1 in any of the lines, cytochrome c release was detected in cytosolic fractions of the lines after serum deprivation for 3 or 4 hours. These results strongly suggest that keloid fibroblasts are predisposed to apoptosis and cytochrome c release and that caspase-9 activation may underlie regulation of apoptosis in keloid fibroblasts in vivo.     

胞嘧啶脱氨酶基因修饰神经干细胞及其表达的离体实验研究

目的 探讨胞嘧啶脱氨酶(cytimidine deaminase，CD)基因修饰神经干细胞及其基因表达。方法 通过构建真核表达质粒pCMVCD，限制性内切酶消化鉴定后，采用Lipofectamine 2000脂质体介导法转染新生大鼠室管膜下区神经干细胞(Neural stem cells，NSCs)，G418筛选阳性克隆，加入不同浓度的5-氟胞嘧啶(5-Flourocytosine，5-FC)，MTT比色法测定NSCs的生存率。结果 本实验成功地培养并鉴定了神经干细胞，并将CD基因成功地转染了神经干细胞，G418阳性NSCs对低浓度5-FC高度敏感。结论 CD基因修饰神经干细胞的离体实验研究为干细胞治疗研究提供依据。     

Antimetastatic Activity of Polymeric RGDT Peptides Conjugated with Poly(ethylene glycol)

Polymeric peptides containing defined repetitive or cyclic structures of RGDT sequence, (RGDT)_n (n = 1 to 11) and cyclo(RGDT)_n (n=2 to 4), at a dose of 500 μg exhibited an inhibitory effect on experimental lung metastasis upon co-injection with tumor cells and the magnitude of the effect increased in parallel with the increase of degree of repetition of the RGDT sequence. The conjugation of (RGDT)_n (n = 1, 5, 11) with poly(ethylene glycol), PEG as a polymeric carrier led to enhanced inhibition of lung metastasis in proportion to the degree of RGDT sequence repetition and in a dose-dependent manner. Multiple i.v. administrations of PEG-(RGDT)₁₁, at 2-day and 3-day intervals before the excision of primary tumors, effectively inhibited spontaneous lung metastasis by s.c. inoculation of tumors, whereas (RGDT)₁₁ exhibited inhibition of lung metastasis only when given at 2-day intervals. This indicates that the conjugation of PEG with (RGDT)_n allowed the prolongation of administration interval, implying a sustained inhibitory effect on tumor metastasis. In support of this supposition, a decrease in the arrest of radiolabeled tumor cells in the lungs was observed when PEG-(RGDT)₁₁ was co-injected i.v. with tumor cells, or injected i.v. one day before tumor inoculation. In contrast, (RGDT)₁₁ significantly inhibited the tumor cell arrest in the lungs only upon co-injection with tumor cells. We also noted that (RGDT)_n, cyclo(RGDT)_n and PEG-(RGDT)₁₁ inhibited tumor cell invasion into Matrigel in a concentration-dependent manner and in proportion to the degree of RGDT sequence repetition, indicating that the peptide-mediated antimetastatic effect is partly associated with the anti-invasive potential. Thus, the conjugation of anti-cell adhesive and antimetastatic RGDT peptide with PEG might provide a therapeutically promising basis for the prevention of cancer metastasis (“anti adhesion therapy”).     

Detection of a human chromosomal translocation t(8;9) in a baby with multiple malformations using two-color fluorescence in situ hybridization

A human chromosomal translocation t(8;9) was detected using two-color fluorescence in situ hybridization with probes capable of staining the entire lengths of each of these chromosomes. The chromosome 8 probe was labeled with biotin and detected with Texas red, while the chromosome 9 probe was labeled with AAF and detected with FITC . In normal metaphase spreads, two metaphases from the proband, two red, one green and one part red and part green derivative chromosome were seen. The bicolor chromosome corresponded to translocation of a chromosome 8 segment to the distal part of the q region of one chromosome 9, as originally indicated by banding analysis. In interphase nuclei of the proband, four domains with bright fluorescence were recognized in many nuclei. Two were red, one was green, and the fourth had portions of both colors, indicating the presence of the translocation.     

Arterial embolization as preoperative treatment for pulmonary aspergillosis with hemoptysis

Pulmonary aspergillosis associated with old tuberculosis is generally resistant to treatment. Thus, if patients are treated only with conservative therapy, their condition continues to deteriorate due to repetitive hemoptysis, and may even become critical. Surgical treatment is required for these patients; however, it is extremely difficult to resect the lesion due to severe adhesions to the chest wall and vascular proliferation surrounding the lesion. We performed preoperative arterial embolization, achieving good results in three patients with hemoptysis caused by pulmonary aspergillosis. The feeding arteries were embolized using microcoils and/or gelatin sponges, and a lobectomy was safely carried out in all patients. We concluded that preoperative arterial embolization is a safe and effective technique to prevent massive hemorrhage occurring at the time of surgery. This work was presented at the 11th Annual Meeting of the Japanese Association for Chest Surgery, held in Kyoto, Japan, May 13–14, 1994     

Validity of Electrode Placement at Fpz to Detect Alpha Wave

Abstract: The possibility on placing electrodes at Fpz-A₂ instead of C₃-A₂ was investigated to obtain a more stable configuration avoiding obstruction by the hair. Our original system of alpha wave detection by a microcomputer was used, and a total of 22 all-night hypnograms of five healthy young students waa recorded. Pearson's moment correlation coefficients of alpha wave % between the two positions were 0.780–0.948. Except for one subject, alpha wave % taken at Fpz-A₂ tended to be 3–5% lower than that at C₃-A₂. The above analysis indicates that using EEG electrode position of Fpz-A₂ is valid and useful as a stable electrode configuration for a long-time monitoring.