Aseptic loosening and periprosthetic osteolysis are major problems in artificial hip joint surgery, for which a solution has yet to be found. Biological host response to wear debris combined with cyclic mechanical loading onto the bone bed around hip prosthetic implants has been considered as mechanism responsible for implant-mediated periprosthetic osteolysis. Any type of artificial joint gliding surface continuously produces wear debris, which are derived from implant materials, i. e., ultra-high molecular weight polyethylene, ceramics and metals. Fragmented bone cement between the bone and implants is also a source of debris. Currently, generation of debris is still inevitable, although modern technology provides better biocompatible implants to lessen the debris. Debris induces foreign body reaction in periprosthetic connective tissues. The main loci are synovial regenerating capsular tissues and interface tissues between the bone and implants, where macrophages play an important role. Various cellular mediators and proteinases are produced in the process. The reaction affects periprosthetic bone remodeling and can provoke imbalanced bone metabolism around implants. It weakens the bone and causes periprosthetic osteolysis. In addition, the joint fluid, which is released from the inflamed connective tissues, has osteolytic potential. Pumping effect on gait and poor integration of boneimplant interface allow penetration of the fluid into intact interface, thus enhancing osteolytic reactions around implants. Further studies on interface biology and implant-related osteolysis with modern technique should lead to a better solution to provide longer survivorship of the artificial hip joint.

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The liver is a target organ for lymphoma and other types of tumor cells. Because there is no basement membrane beneath the sinusoidal endothelium, metastasis of lymphomas to the liver may involve interaction of fibronectin on hepatocytes with a fibronectin receptor on lymphoma cells, although no such fibronectin receptors have yet been demonstrated. Recently, I developed a new monoclonal antibody, LAD-4, that recognizes a novel FN receptor in the mouse lymphoma cell line RL-_??_1. LAD-4 partially, but significantly, inhibited both migration and formation of metastasis by lymphoma cells in the liver, as determined by an in-vivo migration assay using radioisotopes and by a metastasis assay involving histological examination. There was a functional difference between LAD-4 and the antibody specific for lymphocyte-function-associated antigen 1. The latter only inhibited metastasis formation by lymphoma cells in the liver without affecting migration.

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We retrospectively reviewed the clinical courses of 12 consecutively-diagnosed cases of localized, nasal NK-cell lymphoma. All patients revealed a phenotype of CD2+CD3 (Leu4)-cytoplasmic CD3ε+CD5-CD45+CD56+. Nine patients were stage I, and three stage II. Seven patients were initially treated with an anthracycline-containing regimen (Group 1). All but one patient failed to achieve a complete response (CR) and died of lymphoma within six months of diagnosis. All patients with B symptoms and/or an elevated serum LDH level in Group 1 died. The remaining five patients were treated first with radiotherapy (Group 2). After radiotherapy, two patients were treated with anthracycline-containing regimens, and one patient was treated with carboplatin, etoposide, ifosfamide, and dexamethasone (DeVIC). Two patients were treated concurrently with radiotherapy and DeVIC (RT-DeVIC): one showed B symptoms, and both had high serum LDH levels. All five patients in Group 2 achieved CR and four patients are alive with no evidence of recurrence. Based on the present study and a review of the literature, radiotherapy followed by, or combined with, chemotherapy is highly recommended as the initial treatment modality for localized nasal NK-cell lymphoma.

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Bartonella Henselae is the causative agent of human cat-scratch disease (CSD). CSD can be diagnosed by histopathological examination, and by the enzyme immunoadsorbant assay (EIA) and polymerase chain reaction (PCR) methods, which detect B. Henselae DNA. Histopathological findings of CSD include granulomatous lymphadenitis with or without abscess formation. We examined 36 specimens of granulomatous lymphadenitis, including 15 abscess-forming granulomatous lymphadenitis, 9 non-abscess-forming granulomatous lymphadenitis, 10 tuberculosis and 2 sarcoidosis by PCR with primers specific for B. Henselae and Bartonella quintana. As controls, we examined 79 cases of non-granulomatous lymphadenitis, including 7 with dermatopathic lymphadenopathy, 18 Kikuchi's lymphadenitis (histiocytic necrotizing lymphadenitis), 18 follicular hyperplasia, 18 paracortical hyperplasia and 18 non-specific lymphadenitis. The PCR method identified B. henselae in 10 of 15 (67%) patients with abscess-forming granulomatous lymphadenitis and 2 of 9 (22%) with non-abscess-forming granulomatous lymphadenitis, but none in tuberculosis, sarcoidosis and non-granulomatous lymphadenitis. B. henselae was persistently detected in all but one patient from the appearance of symptoms to 4 months from onset in patients with abscess-forming and non-abscess-forming granulomatous lymphadenitis. Our results suggest that the PCR method is useful for establishing the diagnosis of CSD by detecting B. henselae.

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Complement receptor type 1 (CR1), and type 2 (CR2) are expressed on the surface of B-cells and follicular dendritic cells (FDCs) in lymphoid follicles of mice. The importance of CR1 and CR2 in humoral immune response is well documented. Retrovirus-induced immunodeficiency syndrome, murine AIDS (MAIDS), results in abnormal humoral immune responses, destruction of lymphoid structures, and loss of FDC functions, namely trapping of antigens (Ags) and their retention on the cell surface. We investigated the expression of CR1 and CR2 in the spleen and lymph nodes of mice with MAIDS. Flow cytometry and immunohistochemistry revealed the existence of a correlation between the decrease in the expression of CR1 and CR2 by B-cells and the progression of the disease. However, expression of CR1 and CR2 by FDCs was maintained in the later stage of the disease in which lymphoid follicles were destroyed and the ability of FDCs to trap and retain Ag was severely impaired or lost. Moreover, FDCs expressing CR1 and CR2 but not FDCs-specific Ag (FDC-M1 antigen) proliferated in destroyed lymphoid structures. Although the ability of FDCs to trap and retain Ag in vivo was impaired, FDCs trapped immune complexes supplemented with complements in cryostat sections. In addition, FDCs proliferating in MAIDS displayed the same ultrastructural characteristic as normal FDCs, and expressed CD23. We conclude that decreased CR1 and CR2 expression in B-cells and continuous CR1 and CR2 expression in dysfunctional FDCs is important in the pathogenesis of MAIDS.

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Past studies of individual kinases have demonstrated that protein phosphorylation plays a crucial role in the intracellular signaling pathway of bacterial lipopolysaccharide (LPS). However, no one has determined how many kinases may be activated collectively by LPS stimulation. We examined the spectrum of protein kinases activated in macrophages in response to LPS. Activity was assessed by a renatuiation method that exploited the eability of proteins denatured with sodium dodcyl sulfate and then blotted onto a membrane to regain enzymatic activity after guanidine treatment. Seven electrophoretically-distinct protein kinases with apparent molecular masses of 78, 74, 62, 59, 58, 52, and 48-kDa were detected in lysates from unstimulated murine peritoneal macrophages. An additional three kinases, with apparent molecular masses of 82, 55, and 46-kDa, were detected when the macrophages were stimulated with LPS. The activation of these protein kinases may be dictated by complex signals that are delivered by receptor complexes, including Toll-like receptor 4. These results should provide a clue to clarifying the pleiotropic action of LPS on macrophages.

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