Expression of membrane-bound and soluble receptor activator of NF-kappaB ligand (RANKL) in human T cells

The receptor activator of NF-kappaB ligand (RANKL) and its receptor RANK are critical regulators for immune responses as well as bone remodeling. RANKL is a type II transmembrane protein that has two forms-a membrane-anchored protein and a secreted protein. In this report, we demonstrate for the first time the kinetical expression of two forms of RANKL in human T cells using two monoclonal antibodies (mAbs) against human RANKL, which we newly derived. Freshly isolated T cells rarely expressed mRANKL, while the activation of T cells induced a substantial but minimal level of mRANKL as well as the accumulation of considerable amounts of sRANKL. The addition of the metalloprotease inhibitor KB-R8301 efficiently suppressed the release of sRANKL from activated T cells or RANKL-transfectants, and reciprocally enhanced the mRANKL expression. The membrane form of RANKL was also expressed on the infiltrating T cells in the rheumatoid synovial fluid and in the gingival tissues of patients with periodontitis. Our results demonstrate that the expression of mRANKL on T cells is strictly limited, and the majority of RANKL protein produced by T cells may be active in the soluble form after shedding. The mAbs that were derived in this study may be useful for investigating the regulation and function of RANKL in immune responses and bone remodeling.     

Photoreceptor differentiation of retinoblastoma: An electron microscopic study of 29 retinoblastomas

Retinoblastomas exhibit a unique form of differentiation to produce cell elements similar to those seen in a photoreceptor cell. An ultrastructural study was performed on 29 cases of retinoblastoma to further clarify the cytologic characteristics of the tumor cells. The age of the retinoblastomas averaged 17.1 months and the tumor cells showing photo-receptor differentiation were demonstrated in 10 cases (35%). The findings were especially notable in retinoblastomas with Flexner-Wintersteiner rosette formation (seven cases, 28%). Similar photoreceptor differentiation was also evident in solid cell clusters without rosette formation (four cases, 14%). The presence of photoreceptor elements was assumed to be significantly frequent both in Flexner-Wintersteiner rosettes and in the solid cell clusters. The cell cytoplasm also showed proliferation of long mitochondria and microtubules, reflecting photoreceptor differentiation. The hereditary-type retinoblastoma showed more advanced cell differentiation than the non-hereditary type. Photoreceptor differentiated retinoblastoma showed rather indolent growth compared with the undifferentiated type, and the former can expect a curative treatment by operation. These observations provide additional findings of the biological nature of retinoblastomas.     

VAMP2 is expressed in myogenic cells during rat development

Vesicle-associated membrane protein 2 (VAMP2) is a member of the SNARE family of proteins that regulate the intracellular vesicle fusion process. This study investigated the developmental expression of VAMP2 in the rat embryo. In the trunk, VAMP2 was primarily found in the heart on embryonic day (E) 10. On E12.5, VAMP2 expression was found in nerve fibers, somites, and heart. In somites, epithelial cells in the dorsomedial lip, and elongated myoblasts in myotome were positive for VAMP2. On E16.5, VAMP2 was expressed in the heart, nerve fibers, and skeletal muscles. In skeletal muscles, multinuclear myotubes were positive for VAMP2. In the head, where muscles are derived both from somitic and non-somitic origin, VAMP2 was found in myotubes of the extrinsic ocular muscles and masseter muscle on E16.5. These findings suggest the involvement of VAMP2 in the development of skeletal muscles of somitic and non-somitic origins.     

Structure and expression of tomato mitochondrial genes coding for tRNACys (GCA), tRNAAsn (GUU) and tRNATyr (GUA): A native tRNACys gene is present in dicot plants but absent in monocot plants

Summary The nucleotide sequences of tRNA^Asn (GUU) and tRNA^Tyr (GUA) genes from tomato mitochondria and their flanking regions have been determined. The tomato mitochondrial tRNA^Asn gene is located 2.1 kb downstream from the tRNA^Cys gene reported previously (Izuchi and Sugita 1989) and shows a nearly complete identity with the corresponding chloroplast gene. The tRNA^Tyr gene, which shows only 73% homology with the corresponding chloroplast gene, has to be considered a native mitochondrial tRNA gene and is 535 bp from the chloroplast-like tRNA^Asn gene on the same strand. Northern hybridization analysis revealed that the three tRNA genes are transcribed in tomato mitochondria. Southern hybridization analysis of tomato, sugar beet, rice and wheat mitochondrial DNAs, with oligonucleotide probes for mitochondrial or chloroplast tRNA genes, demonstrated that the mitochondrial tRNA^Cys gene found in tomato is present in dicot plants but not in monocots. On the other hand, a chloroplast-like tRNA^Cys gene exists in monocot plants.     

Airway occlusion pressure (P0.1) — A useful predictor for the weaning outcome in patients with acute respiratory failure —

Twenty-five patients who required mechanical ventilatory support (MVS) after major surgery or severe burns were studied to determine whether airway occlusion pressure (P_0.1) is a clinically useful indicator to predict the success or failure of the weaning trial. A total of 33 weaning trials were attempted on these patients. Of the 33 trials, 24 were followed by successful weaning and 9 by failure. Although the success group, when compared with the failure group, had a lower respiratory rate (P 0.001), a lower minute ventilation (P 0.001), a higher maximal voluntary ventilation to minute ventilation ratio (P 0.01) and a higher forced vital capacity (P 0.05), no threshold values separated the success from the failure group. The alveolar-arterial P_{O 2} gradient, with an Fi _{O 2} of 1.0, in weaning success and failure showed no statistical difference. In contrast, all patients in the success group had a P_0.1 of less than 3.5cmH₂O and those in the failure group had a P_0.1 of greater than 3.5cmH₂O (P 0.001). We conclude that P_0.1 is a clinically superior indicator for discontinuing MVS in patients with acute respiratory failure.(Okamoto K, Sato T, Morioka T: Airway occlusion pressure (P_0.1)—A useful predictor for the weaning outcome in patients with acute respiratory failure—. J Anesth 4: 95–101, 1990)     

Evaluation of conventional weaning criteria in patients with acute respiratory failure

We evaluated the reliability of conventional weaning criteria from a ventilator during 33 weaning trials on 25 patients with acute respiratory failure (ARF). Of 13 criteria, a ratio of maximal voluntary ventilation to minute ventilation (MV) 2, a vital capacity 12ml·kg^–1, a spontaneous respiratory rate 25 breaths·min^–1, and a MV 10l·min^–1 appeared to be useful for predicting successful weaning outcome. However, even using those criteria, there were many falsely-negative cases. The alveolar-arterial P_{O 2} gradient 350mmHg at an Fi _{O 2} 1.0 was not useful as a predictor of weaning outcome. The present study demonstrates that conventional criteria are frequently inaccurate for predicting weaning outcomes and suggests that the use of some of these criteria may unnecessarily prolong the length of ventilator support. Since ventilation of most patients with poor oxygenation can be successfully discontinued by placing them on a continuous positive airway pressure system, these results suggest that the improvement of oxygenation is not an indispensable prerequisite for weaning from mechanical ventilators.(Okamoto K, Iwamasa H, Dogomori H, et al.: Evaluation of conventional weaning criteria in patients with acute respiratory failure. J Anesth 4: 213–218, 1990)     

A case of dermatofibrosarcoma protuberans in the skin over the breast

Dermatofibrosarcoma protuberans (DFSP) is a slow-growing but locally aggressive, fibrous tumor that has a high rate of local recurrence after surgical resection. This tumor occurs most commonly in the trunk and proximal extremities. In this report we present a case of dermatofibrosarcoma protuberans in the skin over the breast which was re-excised after pathological diagnosis, considering cosmetic aspects. Only three other cases of dermatofibrosarcoma protuberans of the anterior chest wall have been encountered in our hospital, and all of these cases were male. The presence of this tumor in the skin over the breast appears to be rare in females. Careful complete resection is recommended for this type of tumor.     

Handlebar hernia with intra-abdominal extraluminal air presenting as a novel form of traumatic abdominal wall hernia: Report of a case

An 18-year-old male was admitted to our Emergency Department with a traumatic abdominal wall hernia (TAWH) of the left lower quadrant (LLQ) after suffering hypogastric blunt injury and urogenital lacerations in a motorcycle accident. Upright chest X-ray showed a small amount of right infradiaphragmatic free air, and a computed tomographic (CT) scan demonstrated an abdominal wall hernia. At surgery, no impairment was found in the digestive tract, and an abdominal herniorrhaphy was performed. It is suggested that the free air had passed through a connection between the scrotal laceration and the contralateral abdominal defect via the subcutaneous space and was palpated as emphysema. This is a new type of TAWH, which suggests that blunt abdominal trauma may result in negative pressure in the subcutaneous and peritoneal cavity, and this could reflect the pathophysiology of TAWH.     

Bone marrow transplantation attenuates murine IgA nephropathy: role of a stem cell disorder

BACKGROUND: The pathogenesis of IgA nephropathy is still obscure. The aim of this study was to investigate whether the fundamental pathogenesis of IgA nephropathy lies in bone marrow stem cells (BMCs). METHODS: We used donors of two different strains for bone marrow transplantation (BMT) into mice with a high content of serum IgA (ddY strain, HIGA mice), a murine model of IgA nephropathy. One group (B6-->HIGA, N = 5) received BMCs of C57BL/6j (B6) mice, and the other (HIGA-->HIGA, N = 8) were reconstituted with BMCs of HIGA mice. RESULTS: Twenty-six weeks after BMT, in B6-->HIGA mice, mesangial deposits of IgA and C3 were statistically milder than those in HIGA-->HIGA mice. Light microscopic observations disclosed that glomerular sclerosis and mesangial matrix expansion in B6-->HIGA mice were decreased compared with those in HIGA-->HIGA mice. These B6-->HIGA mice also excreted less urinary albumin than HIGA-->HIGA mice. Furthermore, serum levels of IgA in B6-->HIGA mice were markedly lower than those in HIGA-->HIGA mice. Size analysis of serum IgA revealed that macromolecular IgA were notably lower in B6-->HIGA mice than in HIGA-->HIGA mice. CONCLUSIONS: Our results suggest that qualitative and quantitative changes of serum IgA are determined at the level of stem cells, and that BMT from normal donors can attenuate glomerular lesions in HIGA mice. This approach may offer a new avenue to study the pathogenesis of IgA nephropathy.     

Effect of ticlopidine on exercise-induced platelet aggregation and exercise tolerance time in patients with ischemic heart disease

Platelet aggregation is one of the most important mechanisms for acute myocardial infarction during exercise. We sought to evaluate the effect of ticlopidine (TP) on platelet aggregation (PA) during exercise in patients with ischemic heart disease (IHD). We studied 38 patients with IHD, 26 patients with effort angina pectoris, and 12 patients with a previous myocardial infarction. In protocol I, subjects were divided into two groups. Drugs altering platelet aggregation were withheld 2-4 weeks before the study in 25 patients (control group). TP (200 mg/day) was administered for 7 days in 13 patients (ticlopidine group). A symptom-limited modified Bruce protocol treadmill exercise test was performed. PA was measured at rest and after exercise by using optical densitometry induced by adenosine diphosphate (ADP). PA ratio (percentage of maximum) was compared. In protocol II, in 12 patients, treadmill exercise test and PA measurement were performed with and without TP. PA significantly increased after exercise in control (from 51.7+/-23.3% to 64.4+/-27.7%, p < 0.01) and ticlopidine (from 31.9+/-10.5% to 42.0+/-20.4%, p < .01) groups; however, its grade was lower in the ticlopidine group than in the control group. After exercise, PA was lower in the ticlopidine group than in control group (42.0+/-20.4% vs. 64.4+/-27.7%; p < 0.01). In the same patients, PA was lower with TP than without TP after exercise. Treadmill exercise-tolerance time was greater in the ticlopidine group than in the control group, but not statistically significant (762.3+/-139.2 vs. 711.6+/-169.6 s; NS). Exercise-tolerance time was significantly greater with TP than without TP in same patient (791.7+/-98.9 vs. 733.3+/-152.8 s; p < .05). TP suppressed the increase of PA during exercise and increased the exercise-tolerance time in patients with IHD.