A histological and histochemical study on glycosaminoglycans in epiphysial cartilage of osteochondrodysplasia rat (OCD/OCD).

The osteochondrodysplasia rat, inherited by a single autosomal recessive lethal gene ocd, shows a typical dwarfing syndrome with systemic subcutaneous edema. The skeletal system is most severely affected. The affected neonates are associated with cleft palate, abnormal kidney position and central nerve system malfunction. The present study describes histological and histochemical appearances of the affected epiphysial cartilage. Irregular columnization, thinner hypertrophic zone, swelled chondrocytes, tightly packed chondrocytes with a poor amount of cartilage matrix was found in the affected. The defining characteristic was a wide-spread degenerating area from the resting to hypertrophic zone. The extracellular matrix (ECM) reacted weakly for the glycosaminoglycans (GAGs). A reduced content of sialic acid in the ECM was suggested. It is concluded that the cartilage abnormalities in the ocd/ocd is a new type disease of osteochondrodysplasia possibly due to some defects in GAGs and/or sialic acid metabolism.     

A consideration through the support to resident diabetic patient and care-giver

Our hospital is a National General Hospital with 585 beds. We began the visiting care service from 1990 and four visiting staffs are working at present. The number of targets was 69 in 2002 including 32 patients over 70 years old and 20 care-givers over 70 years old. Visiting care has been conducted to a 72-year-old female with diabetes since July 2000. The patient is in bedridden condition and at the beginning of visiting, she was taking oral medication but the condition was worsen by poor glycemic control and changed to insulin injection from June 2002 after admission to the hospital repeatedly. The patient undergoes the measurement of blood sugar daily and takes meals with 1,200 to 1,400 kcal prepared by her husband. The care-giver is a 71-year-old husband. He was an "all-work, no-play" type of person and had never done the housework, but he started to manage both housework and nursing because of bedridden of his wife. He is a reticent theorist, hates illogical behavior, and does not swayed by other opinions. He has accepted the things which need new knowledge and techniques such as measurement of blood glucose and insulin injection. However, for meals, he only bought side dishes and placed them. Care such as keeping the patient clean was in a same state. The patient consulted and admission to the hospital repeatedly because conditions were not stable. Visiting nurse supported daily life of patient and care-giver especially in nutrition instruction to continue home life. As the result, attitude and behavior toward nursing of care-giver were changed and the patient could continue home life. Therefore we reported here.     

Autoimmune hepatitis complicated with antiphospholipid syndrome in pregnancy

PROBLEM: There are few reports on the association between autoimmune hepatitis (AIH) and antiphospholipid syndrome; only five reports were found on a MEDLINE search between 1966 and 2001. Therefore, the etiology and the optimal treatment of them are not clear. METHOD OF STUDY: We encountered a case of AIH complicated by antiphospholipid syndrome in pregnancy. We present the clinical course and treatment of this case, and discuss some problems in managing such a patient. RESULTS: The patient received low-dose prednisolone and low-dose aspirin and delivered a live-born infant at term without any adverse effects. CONCLUSION: In this case, there was no relation between the variation of alanine aminotransferase (ALT) and the one of beta2-glycoprotein I (GPI)-dependent anticardiolipin antibody. It is supposed that there was no relation between the activity of AIH and the one of antiphospholipid syndrome, and it is also supposed that one is not secondary to the other.     

Hyperimmunoglobulinemia D in idiopathic retinal vasculitis

Background: We examined four patients who exhibited both idiopathic retinal vasculitis and elevated serum IgD levels. Uveitis caused by Behçet's disease is also associated with high levels of serum IgD. Therefore, the clinical features of these patients were investigated and the possible relationship between retinal vasculitis and elevated serum IgD was examined after undertaking a study of increased IgD levels in patients diagnosed with uveitis. Methods: The study population was composed of 110 patients: 49 with Behçet's disease, 15 with sarcoidosis, 10 with Vogt-Koyanagi-Harada disease, and 36 with other forms of uveitis. IgD measurements were performed using modifications of the latex photometric immunoassay. Surface IgD (sIgD) expression in peripheral lymphocytes was determined by immunofluorescence, and the correlation between serum IgD levels and the percentage of sIgD-positive cells was examined. Results: Twelve of the 110 patients had an elevated serum IgD. Eight of the 12 had Behçet's disease, and 4 were diagnosed with idiopathic retinal vasculitis. These 4 patients were HLA-A24+ females whose ages ranged from 8 to 25 years. A linear correlation between the serum IgD levels and the percentage of sIgD-positive cells was found. Conclusion: Hyperimmunoglobulinemia D state was found in Behçet's disease and idiopathic retinal vasculitis. These diseases may represent a new clinical entity characterized by signs of retinal vasculitis and hyperimmunoglobulinemia D that results from abnormal B cell activation and immune complex-mediated responses.     

Relationship between leukotriene C4 and an uteroglobin-like protein in nasal and tracheobronchial mucosa of children. Implication in acute respiratory illnesses

Secretions from the nose and nasopharynx (NPS) are more readily accessible than tracheobronchial secretions (TBS) for clinical investigations, but it is unclear whether changes in mediator release in the nasopharynx reflect similar changes in the tracheobronchial tree. In order to clarify this question, NPS and TBS were taken from 20 children with tracheotomy and tested for the presence of leukotriene C4 (LTC4) and uteroglobin-like protein (UTG-LP). LTC4 and UTG-LP were measured both when the children were healthy and when they had clinical evidence of an acute respiratory tract illness. The mean concentration of LTC4 in NPS and TBS increased during illness although the mean concentration in NPS was significantly higher than in TBS during respiratory illness. In healthy children UTG-LP was detected only in TBS. During acute respiratory illness the concentration of UTG-LP in TBS decreased but remained significantly higher than in NPS. Data presented in this study indicate that changes in the LTC4 concentration in NPS appear to reflect changes in LTC4 concentration in TBS although the levels of LTC4 in NPS were significantly higher than in TBS. An inverse correlation between the concentrations of LTC4 and UTG-LP in NPS and TBS was demonstrated.     

Effective and safe gene therapy for colorectal carcinoma using the cytosine deaminase gene directed by the carcinoembryonic antigen promoter.

We have recently isolated carcinoembryonic antigen (CEA) promoter regions consisting of 419 bp and 204 bp from CEA-producing human colorectal carcinoma (CRC). We constructed CEA419/CD and CEA204/CD retroviruses carrying the bacterial cytosine deaminase (CD) gene directed by the CEA promoter regions. pCD2 retroviruses carrying the CD gene directed by the retrovirus long terminal repeat promoter were also used. CEA419/CD or CEA204/CD retrovirus-infected CRC cells were found to be susceptible to 5-fluorocytosine (5-FC), while non-CRC cells infected with the same retroviruses were not. CD-transduced CRC xenografts in nude mice were sensitive to 5-FC treatment, resulting in arrest of tumor growth. When mice with intraperitoneally disseminated CRCs were given intraperitoneal injections of CEA419/CD retrovirus-producing cells followed by 5-FC treatment, significantly prolonged survival rates were observed compared with animals injected with pCD2 retrovirus-producing cells followed by 5-FC treatment. Importantly, bone marrow suppression was not observed in animals injected with CEA419/CD retrovirus-producing cells and 5-FC, while profound bone marrow suppression was observed in those injected with pCD2 retrovirus-producing cells and 5-FC. These results indicate that effective and safe in vivo gene therapy for advanced CRC may be feasible by transferring the CD gene controlled by the CEA promoter followed by 5-FC treatment.     

Development of an ex vivo cellular model of rheumatoid arthritis: Critical role of cd14‐positive monocyte/macrophages in the development of pannus tissue

Objective

To establish an ex vivo cellular model of pannus, the aberrant overgrowth of human synovial tissue (ST).

Methods

Inflammatory cells that infiltrated pannus tissue from patients with rheumatoid arthritis (RA) were collected without enzyme digestion, and designated as ST‐derived inflammatory cells. Single‐cell suspensions of ST‐derived inflammatory cells were cultured in medium alone. Levels of cytokines produced in culture supernatants were measured using enzyme‐linked immunosorbent assay kits. ST‐derived inflammatory cells were transferred into the joints of immunodeficient mice to explore whether these cells could develop pannus. CD14 and CD2 cells were depleted by negative selection.

Results

Culture of ST‐derived inflammatory cells from 92 of 111 patients with RA resulted in spontaneous reconstruction of inflammatory tissue in vitro within 4 weeks. Ex vivo tissue contained fibroblasts, macrophages, T cells, and tartrate‐resistant acid phosphatase–positive multinucleated cells. On calcium phosphate–coated slides, ST‐derived inflammatory cell cultures showed numerous resorption pits. ST‐derived inflammatory cell cultures continuously produced matrix metalloproteinase 9 and proinflammatory cytokines associated with osteoclastogenesis, such as tumor necrosis factor α, interleukin‐8, and macrophage colony‐stimulating factor. More importantly, transferring ST‐derived inflammatory cells into the joints of immunodeficient mice resulted in the development of pannus tissue and erosive joint lesions. Both in vitro development and in vivo development of pannus tissue by ST‐derived inflammatory cells were inhibited by depleting CD14‐positive, but not CD2‐positive, cells from ST‐derived inflammatory cells.

Conclusion

These findings suggest that overgrowth of inflammatory cells from human rheumatoid synovium simulates the development of pannus. This may prove informative in the screening of potential antirheumatic drugs.