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Human γδ T cells can recognize and respond to a wide variety of stress-induced antigens, thereby developing innate broad anti-tumor and anti-infective activity. 1 The majority of γδ T cells in peripheral blood have the Vγ9Vδ2 T cell receptor. These cells recognize antigen in a major histocompatibility complex-independent manner and develop strong cytolytic and Th1-like effector functions. 1 Therefore, γδ T cells are attractive candidate effector cells for cancer immunotherapy. Vγ9Vδ2 T cells respond to phosphoantigens such as (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), which is synthesized in bacteria via isoprenoid biosynthesis; 2 and isopentenyl pyrophosphate (IPP), which is produced in eukaryotic cells through the mevalonate pathway. 3 In physiological condition, the generation of IPP in nontransformed cell is not sufficient for the activation of γδ T cells. Dysregulation of mevalonate pathway in tumor cells leads to accumulation of IPP and γδ T cells activation. 3 Because aminobisphosphonates (such as pamidronate or zoledronate) inhibit farnesyl pyrophosphate synthase (FPPS), the enzyme acting downstream of IPP in the mevalonate pathway, intracellular levels of IPP and sensitibity to γδ T cells recognition can be therapeutically increased by aminobisphosphonates. IPP accumulation is less efficient in nontransfomred cells than tumor cells with a pharmacologically relevant concentration of aminobisphosphonates, that allow us immunotherapy for cancer by activating γδ T cells with aminobisphosphonates. 4 Interestingly, IPP accumulates in monocytes when PBMC are treated with aminobisphosphonates, because of efficient drug uptake by these cells. 5 Monocytes that accumulate IPP become antigen-presenting cells and stimulate Vγ9Vδ2 T cells in the peripheral blood. 6 Based on these mechanisms, we developed a technique for large-scale expansion of γδ T cell cultures using zoledronate and interleukin-2 (IL-2). 7 Other methods for expansion of γδ T cells utilize the synthetic phosphoantigens bromohydrin pyrophosphate (BrHPP) 8 or 2-methyl-3-butenyl-1-pyrophosphate (2M3B1PP). 9 All of these methods allow ex vivo expansion, resulting in large numbers of γδ T cells for use in adoptive immunotherapy. However, only zoledronate is an FDA-approved commercially available reagent. Zoledronate-expanded γδ T cells display CD27 -CD45RA -effector memory phenotype and thier function can be evaluated by IFN-γ production assay. 7

Background We encountered 15 cases of Helicobacter cinaedi (H. cinaedi) infection between March and July 2008. Patient, Method, and Result The underlying diseases were hematological malignancies in a majority of cases, many of which received chemotherapy. All patients had a fever. The fever was followed by cellulitis in three, a skin rash in six, pain in the lower limbs in three, and diarrhea in three cases. We analyzed the bacterial 23S rRNA genes. The fifteen strains were divided according to base sequence into Groups A, B, and C, respectively. All four cases in Group A were women and all ten in Group C were men, indicating that the gender of the patient corresponded precisely to the genotypes of the separated bacilli in these two groups. These findings also suggested the strong possibility of nosocomial spread. Conclusion It is highly likely that H. cinaedi infections have been overlooked due to the difficulties encountered in culturing the bacterium. The possibility of septicemia caused by H. cinaedi should be suspected especially in immunocompromised patients such as those undergoing chemotherapy, with symptoms such as fever, rash, arthritis, cellulitis, leg pain, and other systemic or local symptoms.

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Summary:We analyzed the incidence and risk factors for chronic graft-versus-host disease (GVHD) in 265 children undergoing allogeneic stem cell transplantation (SCT) who survived longer than 3 months post SCT. Patients transplanted from HLA-mismatched related donors and matched unrelated donors were included. Fifty-five patients developed chronic GVHD between 1 and 25 months after SCT, and the 5-year cumurative incidence of chronic GVHD was 22%. By multivariate analysis, acute GVHD (P = 0.004), malignant disease (P = 0.004), recipient age (у10 years) (P = 0.01) and a female donor to male recipient (P = 0.035) were significant risk factors for chronic GVHD. When acute GVHD was excluded from the multivariate analysis, malignant disease (P = 0.002) and older recipient age (P = 0.007) were identified. The incidence of chronic GVHD in this childhood study was lower than that observed in adults, and recipient age was an important factor in childhood SCT. The high incidence associated with malignant disease may be affected by changes in GVHD prophylaxis in order to ensure graft-versus-tumor effects. Bone Marrow Transplantation (2001) 27, 727-730.

The objective of this study was to clarify the long-term outcome in patients with lupus nephritis (LN) according to the International Society of Nephrology and Renal Pathology Society classification. This retrospective analysis comprised 186 Japanese patients given a diagnosis of LN by renal specimen with a mean observation period of 12 years. Primary end point was defined as death or end-stage renal disease, and standardized mortality ratios were calculated. Five patients presented with histopathological class I, 62 with II, 21 with III or III+V, 73 with IV or IV+V and 25 with V. Fourteen deaths occurred, corresponding to an overall standardized mortality ratio of 3.59 (95% confidence interval 2.02-5.81, p < 0.0001). Kaplan-Meier analysis revealed a 10-year overall survival of 95.7%. Nephrotic proteinuria (≥3.5 g/day) at baseline was identified as an independent poor prognostic factor for overall survival in Cox regression analysis. Kaplan-Meier analysis revealed a 10-year renal survival as 94.3%. Male gender and nephrotic proteinuria at baseline were identified as independent poor prognostic factors for renal survival in Cox regression analysis. In conclusion, LN was associated with a 3.59-fold increase in mortality compared with the general population. Male gender and nephrotic proteinuria were predictive for poor renal outcome.

Our results suggest that immunosuppression intensity, sufficient to induce transient suppression of thymic function, is attributable to the feasible clinical response in patients with SSc treated with autologous HSCT. Appropriate monitoring of sjTREC values may predict clinical benefits in transplanted SSc patients after autologous HSCT.

Background: Hypoxia and decreased blood supply have been proposed as risks for tendon rupture. Visualization of the vascularity of intact and torn rotator cuffs would be useful for improving treatments for rotator cuff tear. Purpose:To assess vascularity inside a tendon or an adjacent rotator cuff insertion point in patients differing in age and extent of damage to the tendon.Study Design: Cross-sectional study. Methods:Ten volunteers (all men) and 15 patients (10 men, 5 women) consented to participate in the study. Contrast agent for enhanced ultrasound was injected intravenously. Enhanced ultrasound images of the torn cuff and the contralateral shoulder were recorded for 1 minute. Four small regions of interest, the articular and bursal sides of the tendon and the medial and lateral sides of the bursa, were studied on all shoulders.Results: There was a significant decrease in blood flow in the intratendinous region in elderly subjects compared with young subjects but age had no effect on blood flow in bursal tissue. Blood flow in ruptured rotator cuffs did not differ from that in intact rotator cuffs. The intraclass correlation coefficient for intraobserver reproducibility was 0.82 (95% confidence interval, 0.77 to 0.86). Conclusions:The findings of this investigation were the hypovascular pattern in Cuff Vascularity with Contrast-Enhanced Ultrasound 3 intratendinous tissue compared with the subacromial bursa, the age-related decrease in intratendinous vascularity, and the hypovascular pattern in the tendon, regardless of rupture of the tendon.Clinical Relevance: Clarification of vascular patterns inside or around the torn ends of a rotator cuff will assist in the development of successful treatments for torn rotator cuffs.