Selective Immunomodulation: Utilization of CD29/VLA Molecules

Abstract: Accumulating evidence suggests that the VLA/ CD29 molecule plays an important role in T-cell costim-ulation, and CD4 ⁺ CD29/VLA ⁺ memory T cells play a key role in induction of CD8 killer effector T cells which are considered to be a major population involved in graft rejection. To target limited elements of the T-lymphocyte population, we have described the preparation of a bi-specific antibody-toxin conjugate designed to target CD4 ⁺ CD29 ⁺ memory T cells. We also showed that the solid-phase crosslinking of VLA-4 by the antibody against this molecule or by its ligand, the CS-1 region of fibronectin, stimulates tyrosine phosphorylation of 140, 120-105, 80-70, 60-55, 50, and 45 kilodalton proteins. In addition, we identified the ppl40 protein as PLCγ, ppl20 protein as ppl25^FAK, pp70 and pp50 proteins as paxillin, and pp60-55 proteins as pp59^fyn and pp56^lck, and pp45 as MAP kinase, respectively. Moreover, we demonstrated that ppl25^FAK is directly associated with paxillin. The paxillin binding domain of ppl25^FAK is homologous to the paxillin binding domain of vinculin. Mutations in the conserved amino acid residues between ppl25^FAK and vinculin result in the loss of paxillin-binding activity. Because VLA/CD29 is preferentially expressed on CD4 memory T cells, the above described system will be used to develop a novel drug design for providing selective immunosuppression useful for organ transplantation. Key Words: Immunomodulation–Graft rejection– Transplantation.     

ROLE OF TUMOR NECROSIS FACTOR IN NEONATAL SEPSIS

ＲＯＬＥＯＦＴＵＭＯＲＮＥＣＲＯＳＩＳＦＡＣＴＯＲＩＮＮＥＯＮＡＴＡＬＳＥＰＳＩＳＳｈｉＹｕａｎ；（史源）ＳｈｅｎＣｈｉｋａｏ；（沈际臬）ＷａｎｇＪｉａｎｇｈｕａｉ；（汪江淮）ＬｉＨｕａｐｉａｎｇ；（李华强）ＱｉｎＳｈｉｗｅｎ；（覃世文）ａｎｄＬｉｕ...     

A new ultrasonographic technique for diagnosing deep venous insufficiency—imaging and functional evaluation of venous valves by ultrasonography with improved resolution

This is to demonstrate a new 2D-ultrasonographic technique which enabled clear resolution of deformed valves, visualization of venous reflux and quantitation of valve incompetence. In a 59-year-old Japanese female patient, ultrasonography was done using Aplio, Toshiba Medical Systems Co., Japan, equipped with 8 MHz linear probe capable of differential tissue harmonic imaging to diagnose the cause of her leg edema. Venous ultrasonography using this device at the popliteal venous valve in this patient demonstrated clear view of deformed venous valve and valve separation at one end of valvular agger while the other part of the valve is closed. Color Doppler failed to show venous reflux due to its low velocity. However, the appearance and disappearance of a thrombus-like echo could be imaged using 2D-ultrasonography. In addition, we were able to demonstrate the time-course change of valve opening and closing, and quantitate the valve incompetence using M-mode ultrasonography.     

Deficiency in systemic interleukin-1 receptor antagonist production as an operative risk factor in malnourished elderly patients with colorectal carcinoma

OBJECTIVE: Aging and tumor-related malnutrition are associated with increased inflammatory cytokine levels. However, it is unclear whether this influences the outcomes of surgery. We explored the relationships between cytokines and surgical complications among patients undergoing surgery for colorectal cancer. DESIGN: Laboratory experiment. SETTING: Surgery department of school of medicine. PATIENTS: One hundred patients with colorectal cancer. INTERVENTIONS: The perioperative circulating levels of interleukin (IL)-1beta, IL-6, and IL-1 receptor antagonist (Ra) were determined, and the numbers of circulating lymphocytes and neutrophils were counted. MEASUREMENTS AND MAIN RESULTS: Trends toward increasing postoperative infection were observed among patients who were older and had lower body mass index. Preoperative IL-1Ra and intraoperative blood loss, however, remained the only two independent predictors of postoperative infection. Clinically, patients with low preoperative IL-1Ra most frequently were the elderly with low body mass index. Postoperatively, elderly patients with low body mass index showed an exaggerated IL-6 response, followed by an exaggerated postoperative inflammatory response and increased postoperative loss of body weight. In contrast, normal immunoreactivity was preserved in well-nourished elderly patients. CONCLUSIONS: In colorectal cancer patients undergoing surgery, low preoperative IL-1Ra is associated with postoperative infection. In our patient population, lower IL-1Ra level is commonly observed in the elderly with low body mass index. These findings suggest that postoperative infection, frequently seen in the nutritionally deficient elderly, may be the result of defective immunoinflammatory adaptation system.     

Clinical and epidemiologic analysis of giant cell (temporal) arteritis from a nationwide survey in 1998 in Japan: the first government-supported nationwide survey

OBJECTIVE: To elucidate epidemiologic and clinical manifestations of Japanese patients with giant cell arteritis (GCA), the first nationwide survey for GCA was conducted in 1998 in Japan. METHODS: The first questionnaire on GCA for patients treated in 1997 was sent to 10,717 medical departments in Japan. A total of 177 patients were reported. Among the 177 patients, 66 GCA patients with detailed clinical and epidemiologic features on second survey were analyzed. RESULTS: Prevalence in patients 50 years of age and older in 1997 was 1.47 per 100,000 population in Japan. The average age at onset was 71.5 years old. The male:female ratio was 1:1.7. The association with permanent and complete visual loss (6.5%), jaw claudication (15.2%), and polymyalgia rheumatica (PMR) (30.3%) were low in frequency compared with those reported from other countries. All patients were treated with corticosteroids. Only 3 (4.5%) patients were reported as deceased due to other causes. CONCLUSION: The prevalence of GCA in Japan was revealed to be extremely low compared with other countries. Clinical findings of permanent and complete visual loss, jaw claudication, and PMR were infrequent among Japanese patients with GCA.