Multi-center analysis of calcinosis in children with juvenile dermatomyositis]

OBJECTIVES: To reveal the frequency and the clinical characteristics of dystrophic calcification that occurs in children with juvenile dermatomyositis, multi-center analysis was constructed. METHOD: Fifty children with JDM were enrolled, and 14 of them (28.0%) were complicated with calcinosis. Clinical symptoms and laboratory tests at onset, initial therapy and disease course were compared in children with and without calcinosis. RESULTS: The mean age of the onset of calcinosis was 4.78 +/- 3.33 years, and it was younger than those of children without calcinosis (8.66 +/- 3.85 years) (P = 0.0017). No differences of clinical manifestation except Gower's sign were observed. The frequency of positive anti-nuclear antibody was 7.1% in children with calcinosis and 52.9% without calcinosis (P = 0.0112). The initial therapy of methylprednisolon pulses gave no effects on prognosis of calcium deposition. The calcinosis appeared in 1.56 +/- 1.91 year after the onset of the disease. The various types of calcium deposition including large tumorous clumps, subcutaneous plaques or nodules, sheet-type calcification were deserved. They appeared over knee joints (64.3%), elbow joint (64.3%), and hip processes (50.0%). Calcinosis affecting the subcutaneous tissues frequently resulted in painful superficial ulceration of the overlying skin (42.9%), local infection (50.0%), and limitation of joint movement (14.3%). Although aluminum phosphate was effective in 2 children among 7, no other effective treatment was recommended. In 5 cases, surgical removal of tumorous clumps was operated. Thus, juvenile dermatomyositis is frequently complicated with calcinosis. This type of calcinosis was found to be unlikely to resolve completely, and resulted in severe disability in children.     

Clinical background of cases showing a positive culture of pleural effusion at Shin-Kokura Hospital over a period of 5 years

We investigated the clinical background of patients at Shin-Kokura Hospital who showed a positive culture of pleural effusion during the period from January 1998 through December 2002. Microorganism cultures of the pleural effusions of 127 patients were performed in this 5-year period. Seventeen patients showed a positive microorganism culture from a pleural effusion, and 12 of these patients (70.6%) were 60 years old or more. Ten patients were diagnosed with thoracic empyema. Thirteen patients had an underlying disease such as malignancy (5 cases), diabetes mellitus (4 cases), etc. A purulent effusion and a high concentration of lactic dehydrogenase (LDH) in the pleural fluid were more frequently recognized in the positive-culture group. A total of 21 strains of microorganism were isolated from the 17 patients, including 10 strains of Gram-positive cocci, 6 strains of Gram-negative bacilli, 3 strains of anaerobes, 1 strain of mycobacterium (Mycobacterium tuberculosis), and 1 strain of fungus. Susceptibility to antimicrobial agents was generally good for most of the microorganisms isolated. Of the 17 patients, chest-tube drainage was performed in 13, and 6 needed a surgical operation. Twelve patients improved, but 5 died. In this study, thoracic empyema accounted for 58.8% of the 17 cases with a positive culture of pleural effusion. Of the 10 thoracic empyema patients, 5 patients needed surgical treatment in spite of adequate antimicrobial treatment and chest-tube drainage. Our data indicate that thoracic empyema is still difficult to treat, and thus adequate and rapid treatment is needed for any pleural infection.     

Venous hemangioma of the mesoappendix: Report of a case and a brief review of the Japanese literature

We present herein the rare case of a 48-year-old man in whom an abdominal mass, revealed by celiotomy to be a solid tumor of the mesoappendix, was histologically diagnosed as having a venous hemangioma. To our knowledge, only 18 cases of mesenteric hemangioma have been reported in Japan, including the present case. However, establishing a correct diagnosis preoperatively is extremely difficult despite advanced imaging techniques. In fact, a mesenteric mass was diagnosed preoperatively in only 3 of these 18 cases. Complete excision with or without bowel resection was performed in 16 cases. Interestingly, the histological diagnosis of all the previous cases was cavernous hemangioma, confirming that this report decuments the first case of venous hemangioma of the mesentery in the Japanese literature.     

Augmentation of intrarenal angiotensin II levels in uninephrectomized aldosterone/salt-treated hypertensive rats; renoprotective effects of an ultrahigh dose of olmesartan.

Recent studies have suggested that aldosterone plays a role in the pathogenesis of renal injury. In this study, we investigated whether local angiotensin II (Ang II) activity contributes to the progression of renal injury in aldosterone/salt-induced hypertensive rats. Uninephrectomized rats were treated with 1% NaCl in a drinking solution and one of the following combinations for 6 weeks: vehicle (2% ethanol, s.c.; n=9), aldosterone (0.75 mug/h, s.c.; n=8), aldosterone+Ang II type 1 receptor blocker olmesartan (10 mg/kg/day, p.o.; n=8), or aldosterone+olmesartan (100 mg/kg/day, p.o.; n=9). Aldosterone/salt-treated hypertensive rats exhibited severe proteinuria and renal injury characterized by glomerular sclerosis and tubulointerstitial fibrosis. Aldosterone/salt-induced renal injury was associated with augmented expression of angiotensin converting enzyme and Ang II levels in the renal cortex and medullary tissues. Renal cortical and medullary mRNA expression of transforming growth factor-beta (TGF-beta) and connective tissue growth factor (CTGF) as well as the collagen contents were increased in aldosterone/salt-treated hypertensive rats. Treatment with olmesartan (10 or 100 mg/kg/day) had no effect on blood pressure but attenuated proteinuria in a dose-dependent manner. Olmesartan at 10 mg/kg/day tended to decrease renal cortical and medullary Ang II levels, TGF-beta and CTGF expression, and collagen contents; however, these changes were not significant. On the other hand, an ultrahigh dose of olmesartan (100 mg/kg/day) significantly decreased these values and ameliorated renal injury. These data suggest that augmented local Ang II activity contributes, at least partially, to the progression of aldosterone/salt-dependent renal injury.     

A case of primary hypothyroidism with repeated episodes of respiratory failure

A case of repeated episodes of hypoventilatory respiratory failure accompanied with primary hypothyroidism was reported. A 76-year-old woman was admitted to our hospital due to both disturbance of consciousness and respiratory failure. A diagnosis of primary hypothyroidism complicated with hypoventilatory respiratory failure deterioration due to respiratory infection was made. Supplemental therapy of thyroid hormones improved her general condition, but respiratory failure recurred after interruption of a replacement drug. Cases of unexplained respiratory failure should be differentiated from respiratory failure induced by hypothyroidism.     

DNA synthesis and related enzymes altered in compensatory lung growth in rats.

Left pneumonectomy was performed on 4 week-old male Fischer-344 rats. Changes in DNA biosynthesis and the activities of related enzymes were studied in the contralateral lungs of the pneumonectomized animals (n = 55) and compared with sham-operated (n = 55) and untreated control animals (n = 40) The wet weight of the contralateral lung of the pneumonectomized rats reached that of both lungs of the untreated and sham-operated rats 14 days after the operation. The activities of thymidine kinase and DNA polymerase from the regenerating lungs were elevated on Days 1 and 7. To determine the molecular forms of DNA polymerase in the crude extract, phosphocellulose column chromatography was performed. The type of DNA polymerase with the highest activity was alpha in regenerating lung on Days 1, 3, and 7. These results suggest that DNA replication for cellular proliferation was elevated in the remaining lung after pneumonectomy. In addition, an interlobar difference in DNA biosynthesis was observed in the remaining lung. The increase was especially marked in the cardiac lobe, followed by increases in the DNA content of the remaining lobes on Day 7. From these observations we conclude (1) that increased activity of DNA polymerase alpha is likely to be an initial change in compensatory lung growth, and may be caused by some unknown stimulator in lung tissue, and (2) that DNA biosynthesis may differ among the lobes of the lung, at least until 3 days post-pneumonectomy.     

Adhesion activity of fetal gonadal cells to EGF and discoidin domains of milk fat globule-EGF factor 8 (MFG-E8), a secreted integrin-binding protein which is transiently expressed in mouse early gonadogenesis

MFG-E8, a secreted integrin-binding protein, consists of two EGF domains containing a RGD motif and two discoidin domains. In mouse embryogenesis, MFG-E8 is highly expressed in gonadal stromal cells near mesonephros at 11.5–12.5 dpc, but its function in gonadogenesis has not been characterized. To clarify a possible role of MFG-E8 in developing gonads, we analyzed the adhesion activity of 10.5–15.5 dpc gonadal cells to recombinant proteins of EGF or discoidin domains of MFG-E8. In EGF-coated wells, the gonadal cells at 11.5–12.5 dpc revealed a significantly higher adhesion activity as compared to those at 10.5 and 15.5 dpc, while discoidin domains showed a constant number of the adhered cells throughout these stages. To identify the adhesive cells of 11.5-dpc gonads, immunohistochemistry with anti-SF1/Ad4Bp antibody (a specific marker for supporting, steroidogenic, and coelomic epithelial cells) and staining for alkaline phosphatase (a germ cell marker) were carried out. As a result, EGF domains, as well as discoidin domains, were capable of binding to all three groups of SF1/Ad4Bp-positive and negative somatic cells, and germ cells of 11.5-dpc gonads. These findings therefore suggest that MFG-E8 mediates the cell-to-cell interaction among several somatic cell types and germ cells in mouse early gonadogenesis.     

Viability and osteogenic potential of cryopreserved human bone marrow-derived mesenchymal cells

Human bone marrow-derived mesenchymal cells contain mesenchymal stem cells (MSCs), which are well known for their osteo/chondrogenic potential and can be used for bone reconstruction. This article reports the viability of cryopreserved human mesenchymal cells and a comparison of the osteogenic potential between noncryopreserved and cryopreserved human mesenchymal cells with MSC-like characteristics, derived from the bone marrow of 28 subjects. The viability of cryopreserved mesenchymal cells was approximately 90% regardless of the storage term (0.3 to 37 months). It is clear by fluorescence-activated cell sorter analysis that the cell surface antigens of both noncryopreserved and cryopreserved mesenchymal cells were negative for hematopoietic cell markers such as CD14, CD34, CD45, and HLA-DR but positive for mesenchymal characteristics such as CD29 and CD105. To monitor the osteogenic potential of the cells, such as alkaline phosphatase (ALP) activity and in vitro mineralization, a subculture was conducted in the presence of dexamethasone, ascorbic acid, and glycerophosphate. No difference in osteogenic potential was found between cells with or without cryopreservation treatment. In addition, cells undergoing long-term cryopreservation (about 3 years) maintained high osteogenic potential. In conclusion, cryopreserved as well as noncryopreserved human mesenchymal cells could be applied for bone regeneration in orthopedics.